@article{Butters2024,
abstract = {Multisystem inflammatory syndrome in children (MIS-C) is a severe, hyperinflammatory disease that occurs after exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The underlying immune pathology of MIS-C is incompletely understood, with limited data comparing MIS-C to clinically similar paediatric febrile diseases at presentation. SARS-CoV-2-specific T cell responses have not been compared in these groups to assess whether there is a T cell profile unique to MIS-C. In this study, we measured inflammatory cytokine concentration and SARS-CoV-2-specific humoral immunity and T cell responses in children with fever and suspected MIS-C at presentation (n = 83) where MIS-C was ultimately confirmed (n = 58) or another diagnosis was made (n = 25) and healthy children (n = 91). Children with confirmed MIS-C exhibited distinctly elevated serum IL-10, IL-6, and CRP at presentation. No differences were detected in SARS-CoV-2 spike IgG serum concentration, neutralisation capacity, antibody dependant cellular phagocytosis, antibody dependant cellular cytotoxicity or SARS-CoV-2-specific T cell frequency between the groups. Healthy SARS-CoV-2 seropositive children had a higher proportion of polyfunctional SARS-CoV-2-specific CD4+ T cells compared to children with MIS-C and those with other inflammatory or infectious diagnoses, who both presented a largely monofunctional SARS-CoV-2-specific CD4+ T cell profile. Treatment with steroids and/or intravenous immunoglobulins resulted in rapid reduction of inflammatory cytokines but did not affect the SARS-CoV-2-specific IgG or CD4+ T cell responses in MIS-C. In these data, MIS-C had a unique cytokine profile but not a unique SARS-CoV-2 specific humoral or T cell cytokine response.},
author = {Butters, Claire and Benede, Ntombi and Moyo-Gwete, Thandeka and Richardson, Simone I and Rohlwink, Ursula and Shey, Muki and Ayres, Frances and Manamela, Nelia P and Makhado, Zanele and Balla, Sashkia R and Madzivhandila, Mashudu and Ngomti, Amkele and Baguma, Richard and Facey-Thomas, Heidi and Spracklen, Timothy F and Day, Jonathan and {van der Ross Debbie}, Hamza and Riou, Catherine and Burgers, Wendy A and Scott, Christiaan and Zuhlke, Liesl and Moore, Penny L and Keeton, Roanne S and Webb, Kate},
doi = {10.1016/J.CLIM.2023.109877},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Butters et al. - 2024 - Comparing the immune abnormalities in MIS-C to healthy children and those with inflammatory disease reveals dist.pdf:pdf},
issn = {1521-6616},
journal = {Clinical Immunology},
keywords = {OA,fund{\_}ack,genomics{\_}fund{\_}ack,original},
mendeley-tags = {OA,fund{\_}ack,genomics{\_}fund{\_}ack,original},
month = {feb},
pages = {109877},
pmid = {38141746},
publisher = {Academic Press},
title = {{Comparing the immune abnormalities in MIS-C to healthy children and those with inflammatory disease reveals distinct inflammatory cytokine production and a monofunctional T cell response}},
volume = {259},
year = {2024}
}

Multisystem inflammatory syndrome in children (MIS-C) is a severe, hyperinflammatory disease that occurs after exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The underlying immune pathology of MIS-C is incompletely understood, with limited data comparing MIS-C to clinically similar paediatric febrile diseases at presentation. SARS-CoV-2-specific T cell responses have not been compared in these groups to assess whether there is a T cell profile unique to MIS-C. In this study, we measured inflammatory cytokine concentration and SARS-CoV-2-specific humoral immunity and T cell responses in children with fever and suspected MIS-C at presentation (n = 83) where MIS-C was ultimately confirmed (n = 58) or another diagnosis was made (n = 25) and healthy children (n = 91). Children with confirmed MIS-C exhibited distinctly elevated serum IL-10, IL-6, and CRP at presentation. No differences were detected in SARS-CoV-2 spike IgG serum concentration, neutralisation capacity, antibody dependant cellular phagocytosis, antibody dependant cellular cytotoxicity or SARS-CoV-2-specific T cell frequency between the groups. Healthy SARS-CoV-2 seropositive children had a higher proportion of polyfunctional SARS-CoV-2-specific CD4+ T cells compared to children with MIS-C and those with other inflammatory or infectious diagnoses, who both presented a largely monofunctional SARS-CoV-2-specific CD4+ T cell profile. Treatment with steroids and/or intravenous immunoglobulins resulted in rapid reduction of inflammatory cytokines but did not affect the SARS-CoV-2-specific IgG or CD4+ T cell responses in MIS-C. In these data, MIS-C had a unique cytokine profile but not a unique SARS-CoV-2 specific humoral or T cell cytokine response.

@article{Benede2024,
abstract = {SARS-CoV-2 infection in children typically results in asymptomatic or mild disease. There is a paucity of studies on antiviral immunity in African children. We investigated SARS-CoV-2-specific T cell responses in 71 unvaccinated asymptomatic South African children who were seropositive or seronegative for SARS-CoV-2. SARS-CoV-2-specific CD4+ T cell responses were detectable in 83{\%} of seropositive and 60{\%} of seronegative children. Although the magnitude of the CD4+ T cell response did not differ significantly between the two groups, their functional profiles were distinct, with SARS-CoV-2 seropositive children exhibiting a higher proportion of polyfunctional T cells compared to their seronegative counterparts. The frequency of SARS-CoV-2-specific CD4+ T cells in seronegative children was associated with the endemic human coronavirus (HCoV) HKU1 IgG response. Overall, the presence of SARS-CoV-2-responding T cells in seronegative children may result from cross-reactivity to endemic coronaviruses and could contribute to the relative protection from disease observed in SARS-CoV-2-infected children.},
author = {Benede, Ntombi and Tincho, Marius B and Walters, Avril and Subbiah, Vennesa and Ngomti, Amkele and Baguma, Richard and Butters, Claire and Hahnle, Lina and Mennen, Mathilda and Skelem, Sango and Adriaanse, Marguerite and Facey-Thomas, Heidi and Scott, Christiaan and Day, Jonathan and Spracklen, Timothy F and van Graan, Strauss and Balla, Sashkia R and Moyo-Gwete, Thandeka and Moore, Penny L and MacGinty, Rae and Botha, Maresa and Workman, Lesley and Johnson, Marina and Goldblatt, David and Zar, Heather J and Ntusi, Ntobeko A B and Z{\"{u}}hlke, Liesl and Webb, Kate and Riou, Catherine and Burgers, Wendy A and Keeton, Roanne S},
doi = {10.1016/J.ISCI.2023.108728},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Benede et al. - 2024 - Distinct T cell polyfunctional profile in SARS-CoV-2 seronegative children associated with endemic human coronavi.pdf:pdf},
issn = {2589-0042},
journal = {iScience},
keywords = {OA,OA{\_}PMC,fund{\_}ack,genomics{\_}fund{\_}ack,original},
mendeley-tags = {OA,OA{\_}PMC,fund{\_}ack,genomics{\_}fund{\_}ack,original},
month = {jan},
number = {1},
pages = {108728},
pmid = {38235336},
publisher = {Elsevier},
title = {{Distinct T cell polyfunctional profile in SARS-CoV-2 seronegative children associated with endemic human coronavirus cross-reactivity}},
volume = {27},
year = {2024}
}

SARS-CoV-2 infection in children typically results in asymptomatic or mild disease. There is a paucity of studies on antiviral immunity in African children. We investigated SARS-CoV-2-specific T cell responses in 71 unvaccinated asymptomatic South African children who were seropositive or seronegative for SARS-CoV-2. SARS-CoV-2-specific CD4+ T cell responses were detectable in 83% of seropositive and 60% of seronegative children. Although the magnitude of the CD4+ T cell response did not differ significantly between the two groups, their functional profiles were distinct, with SARS-CoV-2 seropositive children exhibiting a higher proportion of polyfunctional T cells compared to their seronegative counterparts. The frequency of SARS-CoV-2-specific CD4+ T cells in seronegative children was associated with the endemic human coronavirus (HCoV) HKU1 IgG response. Overall, the presence of SARS-CoV-2-responding T cells in seronegative children may result from cross-reactivity to endemic coronaviruses and could contribute to the relative protection from disease observed in SARS-CoV-2-infected children.

@article{Kassanjee2024a,
abstract = {There are few data on the real-world effectiveness of COVID-19 vaccines and boosting in Africa, which experienced widespread SARS-CoV-2 infection before vaccine availability. We assessed the association between vaccination and severe COVID-19 in the Western Cape, South Africa, in an observational cohort study of {\textgreater}2 million adults during 2020–2022. We described SARS-CoV-2 testing, COVID-19 outcomes, and vaccine uptake over time. We used multivariable cox models to estimate the association of BNT162b2 and Ad26.COV2.S vaccination with COVID-19-related hospitalization and death, adjusting for demographic characteristics, underlying health conditions, socioeconomic status proxies, and healthcare utilization. We found that by the end of 2022, 41{\%} of surviving adults had completed vaccination and 8{\%} had received a booster dose. Recent vaccination was associated with notable reductions in severe COVID-19 during periods dominated by Delta, and Omicron BA.1/2 and BA.4/5 (sub)lineages. During the latest Omicron BA.4/5 wave, within 3 months of vaccination or boosting, BNT162b2 and Ad26.COV2.S were each 84{\%} effective against death (95{\%} CIs: 57–94 and 49–95, respectively). However, distinct reductions of effectiveness occurred at longer times post completing or boosting vaccination. Results highlight the importance of continued emphasis on COVID-19 vaccination and boosting for those at high risk of severe COVID-19, even in settings with widespread infection-induced immunity.},
author = {Kassanjee, Reshma and Davies, Mary-Ann and Heekes, Alexa and Mahomed, Hassan and Hawkridge, Anthony and Morden, Erna and Jacobs, Theuns and Cohen, Cheryl and Moultrie, Harry and Lessells, Richard and {Van Der Walt}, Nicolette and Arendse, Juanita and Wolter, Nicole and Walaza, Sibongile and Jassat, Waasila and von Gottberg, Anne and Hannan, Patrick and Feikin, Daniel and Cloete, Keith and Boulle, Andrew},
doi = {10.3390/VACCINES12060628/S1},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Kassanjee et al. - 2024 - COVID-19 Vaccine Uptake and Effectiveness by Time since Vaccination in the Western Cape Province, South Afr(2).pdf:pdf},
issn = {2076393X},
journal = {Vaccines},
keywords = {19,2,COVID,CoV,OA,SARS,South Africa,cohort,fund{\_}ack,genomics{\_}fund{\_}ack,observational,original,vaccine effectiveness},
mendeley-tags = {OA,fund{\_}ack,genomics{\_}fund{\_}ack,original},
month = {jun},
number = {6},
pages = {628},
publisher = {MDPI AG},
title = {{COVID-19 vaccine uptake and effectiveness by time since vaccination in the Western Cape province, South Africa: an observational cohort study during 2020–2022}},
url = {https://www.mdpi.com/2076-393X/12/6/628/htm https://www.mdpi.com/2076-393X/12/6/628},
volume = {12},
year = {2024}
}

There are few data on the real-world effectiveness of COVID-19 vaccines and boosting in Africa, which experienced widespread SARS-CoV-2 infection before vaccine availability. We assessed the association between vaccination and severe COVID-19 in the Western Cape, South Africa, in an observational cohort study of \textgreater2 million adults during 2020–2022. We described SARS-CoV-2 testing, COVID-19 outcomes, and vaccine uptake over time. We used multivariable cox models to estimate the association of BNT162b2 and Ad26.COV2.S vaccination with COVID-19-related hospitalization and death, adjusting for demographic characteristics, underlying health conditions, socioeconomic status proxies, and healthcare utilization. We found that by the end of 2022, 41% of surviving adults had completed vaccination and 8% had received a booster dose. Recent vaccination was associated with notable reductions in severe COVID-19 during periods dominated by Delta, and Omicron BA.1/2 and BA.4/5 (sub)lineages. During the latest Omicron BA.4/5 wave, within 3 months of vaccination or boosting, BNT162b2 and Ad26.COV2.S were each 84% effective against death (95% CIs: 57–94 and 49–95, respectively). However, distinct reductions of effectiveness occurred at longer times post completing or boosting vaccination. Results highlight the importance of continued emphasis on COVID-19 vaccination and boosting for those at high risk of severe COVID-19, even in settings with widespread infection-induced immunity.

@article{Hunt2024,
abstract = {The SARS-CoV-2 genome occupies a unique place in infection biology -- it is the most highly sequenced genome on earth (making up over 20{\%} of public sequencing datasets) with fine scale information on sampling date and geography, and has been subject to unprecedented intense analysis. As a result, these phylogenetic data are an incredibly valuable resource for science and public health. However, the vast majority of the data was sequenced by tiling amplicons across the full genome, with amplicon schemes that changed over the pandemic as mutations in the viral genome interacted with primer binding sites. In combination with the disparate set of genome assembly workflows and lack of consistent quality control (QC) processes, the current genomes have many systematic errors that have evolved with the virus and amplicon schemes. These errors have significant impacts on the phylogeny, and therefore over the last few years, many thousands of hours of researchers time has been spent in "eyeballing" trees, looking for artefacts, and then patching the tree. Given the huge value of this dataset, we therefore set out to reprocess the complete set of public raw sequence data in a rigorous amplicon-aware manner, and build a cleaner phylogeny. Here we provide a global tree of 3,960,704 samples, built from a consistently assembled set of high quality consensus sequences from all available public data as of March 2023, viewable at https://viridian.taxonium.org. Each genome was constructed using a novel assembly tool called Viridian (https://github.com/iqbal-lab-org/viridian), developed specifically to process amplicon sequence data, eliminating artefactual errors and mask the genome at low quality positions. We provide simulation and empirical validation of the methodology, and quantify the improvement in the phylogeny. Phase 2 of our project will address the fact that the data in the public archives is heavily geographically biased towards the Global North. We therefore have contributed new raw data to ENA/SRA from many countries including Ghana, Thailand, Laos, Sri Lanka, India, Argentina and Singapore. We will incorporate these, along with all public raw data submitted between March 2023 and the current day, into an updated set of assemblies, and phylogeny. We hope the tree, consensus sequences and Viridian will be a valuable resource for researchers. {\#}{\#}{\#} Competing Interest Statement Gavin Screaton sits on the GSK Vaccines Scientific Advisory Board, consults for AstraZeneca, and is a founding member of RQ Biotechnology.},
author = {Hunt, Martin and Hinrichs, Angie S and Anderson, Daniel and Karim, Lily and Dearlove, Bethany L and Knaggs, Jeff and Constantinides, Bede and Fowler, Philip W and Rodger, Gillian and Street, Teresa L and Lumley, Sheila F and Webster, Hermione and Sanderson, Theo and Ruis, Christopher and {De Maio}, Nicola and Amenga-Etego, Lucas N and Amuzu, Dominic SY and Avaro, Martin and Awandare, Gordon A and Ayivor-Djanie, Reuben and Bashton, Matthew and Batty, Elizabeth M and Bediako, Yaw and {De Belder}, Denise and Benedetti, Estefania and Bergthaler, Andreas and Boers, Stefan A and Campos, Josefina and Carr, Rosina Afua Ampomah and Cuba, Facundo and Dattero, Maria Elena and Dejnirattisai, Wanwissa and Dilthey, Alexander T and Duedu, Kwabena Obeng and Endler, Lukas and Engelmann, Ilka and Francisco, Ngiambudulu M and Fuchs, Jonas and Gnimpieba, Etienne Z and Groc, Soraya and Gyamfi, Jones and Heemskerk, Dennis and Houwaart, Torsten and Hsiao, Nei-yuan and Huska, Matthew and Hoelzer, Martin and Iranzadeh, Arash and Jarva, Hanna and Jeewandara, Chandima and Jolly, Bani and Joseph, Rageema and Kant, Ravi and Ki, Karrie Ko Kwan and Kurkela, Satu and Lappalainen, Maija and Lataretu, Marie and Liu, Chang and Malavige, Gathsaurie Neelika and Mashe, Tapfumanei and Mongkolsapaya, Juthathip and Montes, Brigitte and Molina-Mora, Jose Arturo and Morang'a, Collins M and Mvula, Bernard and Nagarajan, Niranjan and Nelson, Andrew and Ngoi, Joyce Mwongeli and da Paixao, Joana Paula and Panning, Marcus and Poklepovich, Tomas and Quashie, Peter Kojo and Ranasinghe, Diyanath and Russo, Mara and San, James E and Sanderson, Nicholas D and Scaria, Vinod and Screaton, Gavin and Sironen, Tarja and Sisay, Abay and Smith, Darren and Smura, Teemu and Supasa, Piyada and Suphavilai, Chayaporn and Swann, Jeremy and Tegally, Houriiyah and Tegomoh, Bryan and Vapalahti, Olli and Walker, Andreas and Wilkinson, Robert J and Williamson, Carolyn and Consortium, IMSSC2 Laboratory Network and de Oliveira, Tulio and Peto, Timothy EA and Crook, Derrick and Corbett-Detig, Russ and Iqbal, Zamin},
doi = {10.1101/2024.04.29.591666},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Hunt et al. - 2024 - Addressing pandemic-wide systematic errors in the SARS-CoV-2 phylogeny.pdf:pdf},
journal = {bioRxiv},
keywords = {OA,fund{\_}ack,genomics{\_}fund{\_}ack,original},
mendeley-tags = {OA,fund{\_}ack,genomics{\_}fund{\_}ack,original},
month = {apr},
pages = {2024.04.29.591666},
publisher = {Cold Spring Harbor Laboratory},
title = {{Addressing pandemic-wide systematic errors in the SARS-CoV-2 phylogeny}},
url = {https://www.biorxiv.org/content/10.1101/2024.04.29.591666v1 https://www.biorxiv.org/content/10.1101/2024.04.29.591666v1.abstract},
volume = {15},
year = {2024}
}

The SARS-CoV-2 genome occupies a unique place in infection biology – it is the most highly sequenced genome on earth (making up over 20% of public sequencing datasets) with fine scale information on sampling date and geography, and has been subject to unprecedented intense analysis. As a result, these phylogenetic data are an incredibly valuable resource for science and public health. However, the vast majority of the data was sequenced by tiling amplicons across the full genome, with amplicon schemes that changed over the pandemic as mutations in the viral genome interacted with primer binding sites. In combination with the disparate set of genome assembly workflows and lack of consistent quality control (QC) processes, the current genomes have many systematic errors that have evolved with the virus and amplicon schemes. These errors have significant impacts on the phylogeny, and therefore over the last few years, many thousands of hours of researchers time has been spent in "eyeballing" trees, looking for artefacts, and then patching the tree. Given the huge value of this dataset, we therefore set out to reprocess the complete set of public raw sequence data in a rigorous amplicon-aware manner, and build a cleaner phylogeny. Here we provide a global tree of 3,960,704 samples, built from a consistently assembled set of high quality consensus sequences from all available public data as of March 2023, viewable at https://viridian.taxonium.org. Each genome was constructed using a novel assembly tool called Viridian (https://github.com/iqbal-lab-org/viridian), developed specifically to process amplicon sequence data, eliminating artefactual errors and mask the genome at low quality positions. We provide simulation and empirical validation of the methodology, and quantify the improvement in the phylogeny. Phase 2 of our project will address the fact that the data in the public archives is heavily geographically biased towards the Global North. We therefore have contributed new raw data to ENA/SRA from many countries including Ghana, Thailand, Laos, Sri Lanka, India, Argentina and Singapore. We will incorporate these, along with all public raw data submitted between March 2023 and the current day, into an updated set of assemblies, and phylogeny. We hope the tree, consensus sequences and Viridian will be a valuable resource for researchers. ### Competing Interest Statement Gavin Screaton sits on the GSK Vaccines Scientific Advisory Board, consults for AstraZeneca, and is a founding member of RQ Biotechnology.

@article{Kassanjee2024,
abstract = {Background There are few data on the real-world effectiveness of COVID-19 vaccines and boosting in Africa, which experienced high levels of SARS-CoV-2 infection in a mostly vaccine-na{\"{i}}ve population, and has limited vaccine coverage and competing health service priorities. We assessed the association between vaccination and severe COVID-19 in the Western Cape, South Africa. Methods We performed an observational cohort study of {\textgreater}2 million adults during 2020-2022. We described SARS-CoV-2 testing, COVID-19 outcomes, and vaccine uptake over time. We used multivariable cox models to estimate the association of BNT162b2 and Ad26.COV2.S vaccination with COVID-19-related hospitalisation and death, adjusting for demographic characteristics, underlying health conditions, socioeconomic status proxies and healthcare utilisation. Results By end 2022, only 41{\%} of surviving adults had completed vaccination and 8{\%} a booster dose, despite several waves of severe COVID-19. Recent vaccination was associated with notable reductions in severe COVID-19 during distinct analysis periods dominated by Delta, Omicron BA.1/2 and BA.4/5 (sub)lineages: within 6 months of completing vaccination or boosting, vaccine effectiveness was 46-92{\%} for death (range across periods), 45-92{\%} for admission with severe disease or death, and 25-90{\%} for any admission or death. During the Omicron BA.4/5 wave, within 3 months of vaccination or boosting, BNT162b2 and Ad26.COV2.S were each 84{\%} effective against death (95{\%} CIs: 57-94 and 49-95, respectively). However, there were distinct reductions of VE at larger times post completing or boosting vaccination. Conclusions Continued emphasis on regular COVID-19 vaccination including boosting is important for those at high risk of severe COVID-19 even in settings with widespread infection-induced immunity. {\#}{\#}{\#} Competing Interest Statement MD reports grants from Viiv Healthcare, outside the submitted work. CC reports grants from Sanofi Pasteur, US Centers for Disease Control and Prevention (CDC), Wellcome Trust, South African Medical Research Council (SAMRC) and the Bill {\&} Melinda Gates Foundation. NW reports grants from the Bill and Melinda Gates Foundation and Sanofi. SW reports grants from US CDC and Bill and Melinda Gates Foundation. AvG reports grants from the World Health Organisation Regional Office for Africa (WHO-AFRO), US CDC, SAMRC, Fleming Fund, Africa Centres for Disease Control / African Society for Laboratory Medicine. AB reports grants from the US National Institutes for Health, Bill and Melinda Gates Foundation and the Wellcome Trust. {\#}{\#}{\#} Funding Statement This work was supported by funding from the Western Cape Government Department of Health and Wellness for the Western Cape Provincial Health Data Centre, the US National Institutes for Health [R01 HD080465, U01 AI069924], the Bill and Melinda Gates Foundation [1164272, 1191327], the United States Agency for International Development [72067418CA00023], the European Union [101045989], the Grand Challenges ICODA pilot initiative delivered by Health Data Research UK and funded by the Bill {\&} Melinda Gates and Minderoo Foundations [INV-017293], and the Wellcome Trust [203135/Z/16/Z, 222574]. The funders had no role in the study design, data collection, data analysis, data interpretation, or writing of this report. The opinions, findings and conclusions expressed in this manuscript reflect those of the authors alone. {\#}{\#}{\#} Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The Health Research Ethics Committee of the University of Cape Town gave ethical approval for this work (HREC REF 460/2020). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The data are not publicly available due to privacy or ethical restrictions. The data that support the findings of this study can be requested from the Western Cape Provincial Health Data Centre (WCPHDC) [{\textless}https://www.westerncape.gov.za/general-publication/provincial-health-data-centre{\textgreater}]; restrictions apply to the availability of these data.},
author = {Kassanjee, Reshma and Davies, Mary-Ann and Heekes, Alexa and Mahomed, Hassan and Hawkridge, Anthony J and Wolmarans, Milani and Morden, Erna and Jacobs, Theuns and Cohen, Cheryl and Moultrie, Harry and Lessells, Richard J and Walt, Nicolette Van Der and Arendse, Juanita O and Goeiman, Hilary and Mudaly, Vanessa and Wolter, Nicole and Walaza, Sibongile and Jassat, Waasila and von Gottberg, Anne and Hannan, Patrick L and Rousseau, Petro and Feikin, Daniel and Cloete, Keith and Boulle, Andrew},
doi = {10.1101/2024.01.24.24301721},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Kassanjee et al. - 2024 - COVID-19 vaccine uptake and effectiveness by time since vaccination in the Western Cape province, South Africa.pdf:pdf},
journal = {medRxiv},
keywords = {OA,fund{\_}ack,genomics{\_}fund{\_}ack,original},
mendeley-tags = {OA,fund{\_}ack,genomics{\_}fund{\_}ack,original},
month = {jan},
pages = {2024.01.24.24301721},
publisher = {Cold Spring Harbor Laboratory Press},
title = {{COVID-19 vaccine uptake and effectiveness by time since vaccination in the Western Cape province, South Africa: an observational cohort study during 2020-2022}},
url = {https://www.medrxiv.org/content/10.1101/2024.01.24.24301721v1 https://www.medrxiv.org/content/10.1101/2024.01.24.24301721v1.abstract},
volume = {15},
year = {2024}
}

Background There are few data on the real-world effectiveness of COVID-19 vaccines and boosting in Africa, which experienced high levels of SARS-CoV-2 infection in a mostly vaccine-naïve population, and has limited vaccine coverage and competing health service priorities. We assessed the association between vaccination and severe COVID-19 in the Western Cape, South Africa. Methods We performed an observational cohort study of \textgreater2 million adults during 2020-2022. We described SARS-CoV-2 testing, COVID-19 outcomes, and vaccine uptake over time. We used multivariable cox models to estimate the association of BNT162b2 and Ad26.COV2.S vaccination with COVID-19-related hospitalisation and death, adjusting for demographic characteristics, underlying health conditions, socioeconomic status proxies and healthcare utilisation. Results By end 2022, only 41% of surviving adults had completed vaccination and 8% a booster dose, despite several waves of severe COVID-19. Recent vaccination was associated with notable reductions in severe COVID-19 during distinct analysis periods dominated by Delta, Omicron BA.1/2 and BA.4/5 (sub)lineages: within 6 months of completing vaccination or boosting, vaccine effectiveness was 46-92% for death (range across periods), 45-92% for admission with severe disease or death, and 25-90% for any admission or death. During the Omicron BA.4/5 wave, within 3 months of vaccination or boosting, BNT162b2 and Ad26.COV2.S were each 84% effective against death (95% CIs: 57-94 and 49-95, respectively). However, there were distinct reductions of VE at larger times post completing or boosting vaccination. Conclusions Continued emphasis on regular COVID-19 vaccination including boosting is important for those at high risk of severe COVID-19 even in settings with widespread infection-induced immunity. ### Competing Interest Statement MD reports grants from Viiv Healthcare, outside the submitted work. CC reports grants from Sanofi Pasteur, US Centers for Disease Control and Prevention (CDC), Wellcome Trust, South African Medical Research Council (SAMRC) and the Bill & Melinda Gates Foundation. NW reports grants from the Bill and Melinda Gates Foundation and Sanofi. SW reports grants from US CDC and Bill and Melinda Gates Foundation. AvG reports grants from the World Health Organisation Regional Office for Africa (WHO-AFRO), US CDC, SAMRC, Fleming Fund, Africa Centres for Disease Control / African Society for Laboratory Medicine. AB reports grants from the US National Institutes for Health, Bill and Melinda Gates Foundation and the Wellcome Trust. ### Funding Statement This work was supported by funding from the Western Cape Government Department of Health and Wellness for the Western Cape Provincial Health Data Centre, the US National Institutes for Health [R01 HD080465, U01 AI069924], the Bill and Melinda Gates Foundation [1164272, 1191327], the United States Agency for International Development [72067418CA00023], the European Union [101045989], the Grand Challenges ICODA pilot initiative delivered by Health Data Research UK and funded by the Bill & Melinda Gates and Minderoo Foundations [INV-017293], and the Wellcome Trust [203135/Z/16/Z, 222574]. The funders had no role in the study design, data collection, data analysis, data interpretation, or writing of this report. The opinions, findings and conclusions expressed in this manuscript reflect those of the authors alone. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The Health Research Ethics Committee of the University of Cape Town gave ethical approval for this work (HREC REF 460/2020). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The data are not publicly available due to privacy or ethical restrictions. The data that support the findings of this study can be requested from the Western Cape Provincial Health Data Centre (WCPHDC) [\textlesshttps://www.westerncape.gov.za/general-publication/provincial-health-data-centre\textgreater]; restrictions apply to the availability of these data.

@article{Nesamari2024,
abstract = {Ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) evolution has given rise to recombinant Omicron lineages that dominate globally (XBB.1), as well as the emergence of hypermutated variants (BA.2.86). In this context, durable and cross-reactive T cell immune memory is critical for continued protection against severe COVID-19. We examined T cell responses to SARS-CoV-2 approximately 1.5 years since Omicron first emerged. We describe sustained CD4+ and CD8+ spike-specific T cell memory responses in healthcare workers in South Africa (n = 39) who were vaccinated and experienced at least one SARS-CoV-2 infection. Spike-specific T cells are highly cross-reactive with all Omicron variants tested, including BA.2.86. Abundant nucleocapsid and membrane-specific T cells are detectable in most participants. The bulk of SARS-CoV-2-specific T cell responses have an early-differentiated phenotype, explaining their persistent nature. Overall, hybrid immunity leads to the accumulation of spike and non-spike T cells evident 3.5 years after the start of the pandemic, with preserved recognition of highly mutated SARS-CoV-2 variants.},
author = {Nesamari, Rofhiwa and Omondi, Millicent A and Baguma, Richard and H{\"{o}}ft, Maxine A and Ngomti, Amkele and Nkayi, Anathi A and Besethi, Asiphe S and Magugu, Siyabulela F J and Mosala, Paballo and Walters, Avril and Clark, Gesina M and Mennen, Mathilda and Skelem, Sango and Adriaanse, Marguerite and Grifoni, Alba and Sette, Alessandro and Keeton, Roanne S and Ntusi, Ntobeko A B and Riou, Catherine and Burgers, Wendy A},
doi = {10.1016/J.CHOM.2023.12.003},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Nesamari et al. - 2024 - Post-pandemic memory T cell response to SARS-CoV-2 is durable, broadly targeted, and cross-reactive to the hype.pdf:pdf},
issn = {1931-3128},
journal = {Cell Host {\&} Microbe},
keywords = {OA,fund{\_}ack,genomics{\_}fund{\_}ack,original},
mendeley-tags = {OA,fund{\_}ack,genomics{\_}fund{\_}ack,original},
month = {feb},
number = {2},
pages = {162--169},
pmid = {38211583},
publisher = {Cell Press},
title = {{Post-pandemic memory T cell response to SARS-CoV-2 is durable, broadly targeted, and cross-reactive to the hypermutated BA.2.86 variant}},
url = {http://www.ncbi.nlm.nih.gov/pubmed/38211583},
volume = {32},
year = {2024}
}

Ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) evolution has given rise to recombinant Omicron lineages that dominate globally (XBB.1), as well as the emergence of hypermutated variants (BA.2.86). In this context, durable and cross-reactive T cell immune memory is critical for continued protection against severe COVID-19. We examined T cell responses to SARS-CoV-2 approximately 1.5 years since Omicron first emerged. We describe sustained CD4+ and CD8+ spike-specific T cell memory responses in healthcare workers in South Africa (n = 39) who were vaccinated and experienced at least one SARS-CoV-2 infection. Spike-specific T cells are highly cross-reactive with all Omicron variants tested, including BA.2.86. Abundant nucleocapsid and membrane-specific T cells are detectable in most participants. The bulk of SARS-CoV-2-specific T cell responses have an early-differentiated phenotype, explaining their persistent nature. Overall, hybrid immunity leads to the accumulation of spike and non-spike T cells evident 3.5 years after the start of the pandemic, with preserved recognition of highly mutated SARS-CoV-2 variants.

@article{Tegally2023,
abstract = {The Alpha, Beta and Gamma SARS-CoV-2 Variants of Concern (VOCs) co-circulated globally during 2020-21, fueling waves of infections. They were displaced by Delta during a third wave worldwide in 2021, in turn displaced by Omicron in late 2021. In this study, we use phylogenetic and phylogeographic methods to reconstruct the dispersal patterns of VOCs worldwide. We find that source-sink dynamics varied substantially by VOC, and identify countries that acted as global and regional hubs of dissemination. We demonstrate a declining role of presumed origin countries of VOCs to their global dispersal, estimating that India contributed {\textless}15{\%} of Delta exports and South Africa {\textless}1-2{\%} of Omicron dispersal. We estimate that {\textgreater}80 countries had received introductions of Omicron within 100 days of emergence, associated with accelerating passenger air travel and higher transmissibility. Our study highlights the rapid dispersal of highly transmissible variants with implications for genomic surveillance along the hierarchical airline network.},
author = {Tegally, Houriiyah and Wilkinson, Eduan and Tsui, Joseph L-H and Moir, Monika and Martin, Darren and Brito, Anderson Fernandes and Giovanetti, Marta and Khan, Kamran and Huber, Carmen and Bogoch, Isaac I and San, James Emmanuel and Poongavanan, Jenicca and Xavier, Joicymara S and Candido, Darlan da S and Romero, Filipe and Baxter, Cheryl and Pybus, Oliver G and Lessells, Richard and Faria, Nuno R and Kraemer, Moritz U G and de Oliveira, Tulio},
doi = {10.1016/J.CELL.2023.06.001},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Tegally et al. - 2023 - Dispersal patterns and influence of air travel during the global expansion of SARS-CoV-2 variants of concern.pdf:pdf},
issn = {0092-8674},
journal = {Cell},
keywords = {genomics{\_}fund{\_}ack,original},
mendeley-tags = {genomics{\_}fund{\_}ack,original},
month = {jun},
pages = {10.1016/j.cell.2023.06.001},
pmid = {37413988},
publisher = {Cell Press},
title = {{Dispersal patterns and influence of air travel during the global expansion of SARS-CoV-2 variants of concern}},
url = {https://linkinghub.elsevier.com/retrieve/pii/S0092867423006414},
year = {2023}
}

The Alpha, Beta and Gamma SARS-CoV-2 Variants of Concern (VOCs) co-circulated globally during 2020-21, fueling waves of infections. They were displaced by Delta during a third wave worldwide in 2021, in turn displaced by Omicron in late 2021. In this study, we use phylogenetic and phylogeographic methods to reconstruct the dispersal patterns of VOCs worldwide. We find that source-sink dynamics varied substantially by VOC, and identify countries that acted as global and regional hubs of dissemination. We demonstrate a declining role of presumed origin countries of VOCs to their global dispersal, estimating that India contributed \textless15% of Delta exports and South Africa \textless1-2% of Omicron dispersal. We estimate that \textgreater80 countries had received introductions of Omicron within 100 days of emergence, associated with accelerating passenger air travel and higher transmissibility. Our study highlights the rapid dispersal of highly transmissible variants with implications for genomic surveillance along the hierarchical airline network.

@article{Hermans2023,
abstract = {Background: The emergence of genetic variants of SARS-CoV-2 was associated with changing epidemiological characteristics throughout coronavirus disease 2019 (COVID-19) pandemic in population-based studies. Individual-level data on the clinical characteristics of infection with different SARS-CoV-2 variants in African countries is less well documented. Objectives: To describe the evolving clinical differences observed with the various SARS-CoV-2 variants of concern and compare the Omicron-driven wave in infections to the previous Delta-driven wave. Method: We performed a retrospective observational cohort study among patients admitted to a South African referral hospital with COVID-19 pneumonia. Patients were stratified by epidemiological wave period, and in a subset, the variants associated with each wave were confirmed by genomic sequencing. Outcomes were analysed by Cox proportional hazard models. Results: We included 1689 patients were included, representing infection waves driven predominantly by ancestral, Beta, Delta and Omicron BA1/BA2 {\&} BA4/BA5 variants. Crude 28-day mortality was 25.8{\%} (34/133) in the Omicron wave period versus 37.1{\%} (138/374) in the Delta wave period (hazard ratio [HR] 0.68 [95{\%} CI 0.47–1.00] p = 0.049); this effect persisted after adjustment for age, gender, HIV status and presence of cardiovascular disease (adjusted HR [aHR] 0.43 [95{\%} CI 0.28–0.67] p {\textless} 0.001). Hospital-wide SARS-CoV-2 admissions and deaths were highest during the Delta wave period, with a decoupling of SARS-CoV-2 deaths and overall deaths thereafter. Conclusion: There was lower in-hospital mortality during Omicron-driven waves compared with the prior Delta wave, despite patients admitted during the Omicron wave being at higher risk. Contribution: This study summarises clinical characteristics associated with SARS-CoV-2 variants during the COVID-19 pandemic at a South African tertiary hospital, demonstrating a waning impact of COVID-19 on healthcare services over time despite epidemic waves driven by new variants. Findings suggest the absence of increasing virulence from later variants and protection from population and individual-level immunity.},
author = {Hermans, Lucas E and Booysen, Petro and Boloko, Linda and Adriaanse, Marguerite and de Wet, Timothy J and Lifson, Aimee R and Wadee, Naweed and Papavarnavas, Nectarios and Marais, Gert and Hsiao, Nei-yuan and Rosslee, Michael-Jon and Symons, Gregory and Calligaro, Gregory L and Iranzadeh, Arash and Wilkinson, Robert J and Ntusi, Ntobeko A B and Williamson, Carolyn and Davies, Mary-Ann and Meintjes, Graeme A and Wasserman, Sean},
doi = {10.4102/SAJID.V38I1.550},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Hermans et al. - 2023 - Changing character and waning impact of COVID-19 at a tertiary centre in Cape Town, South Africa.pdf:pdf},
issn = {2313-1810},
journal = {Southern African Journal of Infectious Diseases},
keywords = {19,2,COVID,CoV,Delta,Infectious diseases,OA,Omicron,SARS,bacterial,clinical,clinical characteristics,communicable,diagnosis,epidemiology,fund{\_}ack,fungal,genomics{\_}fund{\_}ack,laboratory,observational study,original,parasitic,treatment,viral},
mendeley-tags = {OA,fund{\_}ack,genomics{\_}fund{\_}ack,original},
month = {dec},
number = {1},
pages = {a550},
pmid = {38223432},
publisher = {AOSIS},
title = {{Changing character and waning impact of COVID-19 at a tertiary centre in Cape Town, South Africa}},
url = {https://sajid.co.za/index.php/sajid/article/view/550/1329 https://sajid.co.za/index.php/sajid/article/view/550/1330 https://sajid.co.za/index.php/sajid/article/view/550/1331 https://sajid.co.za/index.php/sajid/article/view/550},
volume = {38},
year = {2023}
}

Background: The emergence of genetic variants of SARS-CoV-2 was associated with changing epidemiological characteristics throughout coronavirus disease 2019 (COVID-19) pandemic in population-based studies. Individual-level data on the clinical characteristics of infection with different SARS-CoV-2 variants in African countries is less well documented. Objectives: To describe the evolving clinical differences observed with the various SARS-CoV-2 variants of concern and compare the Omicron-driven wave in infections to the previous Delta-driven wave. Method: We performed a retrospective observational cohort study among patients admitted to a South African referral hospital with COVID-19 pneumonia. Patients were stratified by epidemiological wave period, and in a subset, the variants associated with each wave were confirmed by genomic sequencing. Outcomes were analysed by Cox proportional hazard models. Results: We included 1689 patients were included, representing infection waves driven predominantly by ancestral, Beta, Delta and Omicron BA1/BA2 & BA4/BA5 variants. Crude 28-day mortality was 25.8% (34/133) in the Omicron wave period versus 37.1% (138/374) in the Delta wave period (hazard ratio [HR] 0.68 [95% CI 0.47–1.00] p = 0.049); this effect persisted after adjustment for age, gender, HIV status and presence of cardiovascular disease (adjusted HR [aHR] 0.43 [95% CI 0.28–0.67] p \textless 0.001). Hospital-wide SARS-CoV-2 admissions and deaths were highest during the Delta wave period, with a decoupling of SARS-CoV-2 deaths and overall deaths thereafter. Conclusion: There was lower in-hospital mortality during Omicron-driven waves compared with the prior Delta wave, despite patients admitted during the Omicron wave being at higher risk. Contribution: This study summarises clinical characteristics associated with SARS-CoV-2 variants during the COVID-19 pandemic at a South African tertiary hospital, demonstrating a waning impact of COVID-19 on healthcare services over time despite epidemic waves driven by new variants. Findings suggest the absence of increasing virulence from later variants and protection from population and individual-level immunity.

@article{Davies2023,
abstract = {Objectives: We aimed to compare the clinical severity of Omicron BA.4/BA.5 infection with BA.1 and ear- lier variant infections among laboratory-confirmed SARS-CoV-2 cases in the Western Cape, South Africa, using timing of infection to infer the lineage/variant causing infection. Methods: We included public sector patients aged ≥20 years with laboratory-confirmed COVID-19 be- tween May 01-May 21, 2022 (BA.4/BA.5 wave) and equivalent previous wave periods. We compared the risk between waves of (i) death and (ii) severe hospitalization/death (all within 21 days of diagnosis) using Cox regression adjusted for demographics, comorbidities, admission pressure, vaccination, and pre- vious infection. Results: Among 3793 patients from the BA.4/BA.5 wave and 190,836 patients from previous waves, the risk of severe hospitalization/death was similar in the BA.4/BA.5 and BA.1 waves (adjusted hazard ratio [aHR] 1.12; 95{\%} confidence interval [CI] 0.93; 1.34). Both Omicron waves had a lower risk of severe out- comes than previous waves. Previous infection (aHR 0.29, 95{\%} CI 0.24; 0.36) and vaccination (aHR 0.17; 95{\%} CI 0.07; 0.40 for at least three doses vs no vaccine) were protective. Conclusion: Disease severity was similar among diagnosed COVID-19 cases in the BA .4/BA .5 and BA .1 pe- riods in the context of growing immunity against SARS-CoV-2 due to previous infection and vaccination, both of which were strongly protective},
author = {Davies, Mary-Ann and Morden, Erna and Rousseau, Petro and Arendse, Juanita and Bam, Jamy-Lee and Boloko, Linda and Cloete, Keith and Cohen, Cheryl and Chetty, Nicole and Dane, Pierre and Heekes, Alexa and Hsiao, Nei-Yuan and Hunter, Mehreen and Hussey, Hannah and Jacobs, Theuns and Jassat, Waasila and Kariem, Saadiq and Kassanjee, Reshma and Laenen, Inneke and Roux, Sue Le and Lessells, Richard and Mahomed, Hassan and Maughan, Deborah and Meintjes, Graeme A and Mendelson, Marc and Mnguni, Ayanda and Moodley, Melvin and Murie, Katy and Naude, Jonathan and Ntusi, Ntobeko A B and Paleker, Masudah and Parker, Arifa and Pienaar, David and Preiser, Wolfgang and Prozesky, Hans and Raubenheimer, Peter and Rossouw, Liezel and Schrueder, Neshaad and Smith, Barry and Smith, Mariette and Solomon, Wesley and Symons, Greg and Taljaard, Jantjie and Wasserman, Sean and Wilkinson, Robert J and Wolmarans, Milani and Wolter, Nicole and Boulle, Andrew},
doi = {10.1016/J.IJID.2022.11.024},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Davies et al. - 2023 - Outcomes of laboratory-confirmed SARS-CoV-2 infection during resurgence driven by Omicron lineages BA.4 and BA.5.pdf:pdf},
issn = {1201-9712},
journal = {International Journal of Infectious Diseases},
keywords = {OA,OA{\_}PMC,OA{\_}repository,fund{\_}ack,genomics{\_}fund{\_}ack,original},
mendeley-tags = {OA,OA{\_}PMC,OA{\_}repository,fund{\_}ack,genomics{\_}fund{\_}ack,original},
month = {feb},
pages = {63--68},
pmid = {36436752},
publisher = {Elsevier},
title = {{Outcomes of laboratory-confirmed SARS-CoV-2 infection during resurgence driven by Omicron lineages BA.4 and BA.5 compared with previous waves in the Western Cape Province, South Africa}},
url = {https://linkinghub.elsevier.com/retrieve/pii/S1201971222006154},
volume = {127},
year = {2023}
}

Objectives: We aimed to compare the clinical severity of Omicron BA.4/BA.5 infection with BA.1 and ear- lier variant infections among laboratory-confirmed SARS-CoV-2 cases in the Western Cape, South Africa, using timing of infection to infer the lineage/variant causing infection. Methods: We included public sector patients aged ≥20 years with laboratory-confirmed COVID-19 be- tween May 01-May 21, 2022 (BA.4/BA.5 wave) and equivalent previous wave periods. We compared the risk between waves of (i) death and (ii) severe hospitalization/death (all within 21 days of diagnosis) using Cox regression adjusted for demographics, comorbidities, admission pressure, vaccination, and pre- vious infection. Results: Among 3793 patients from the BA.4/BA.5 wave and 190,836 patients from previous waves, the risk of severe hospitalization/death was similar in the BA.4/BA.5 and BA.1 waves (adjusted hazard ratio [aHR] 1.12; 95% confidence interval [CI] 0.93; 1.34). Both Omicron waves had a lower risk of severe out- comes than previous waves. Previous infection (aHR 0.29, 95% CI 0.24; 0.36) and vaccination (aHR 0.17; 95% CI 0.07; 0.40 for at least three doses vs no vaccine) were protective. Conclusion: Disease severity was similar among diagnosed COVID-19 cases in the BA .4/BA .5 and BA .1 pe- riods in the context of growing immunity against SARS-CoV-2 due to previous infection and vaccination, both of which were strongly protective

@article{Gonzalez-Rodriguez2023,
abstract = {The emergence of a polybasic cleavage motif for the protease furin in SARS-CoV-2 spike has been established as a major factor for human viral transmission. The region N-terminal to that motif is extensively mutated in variants of concern (VOCs). Besides furin, spikes from these variants appear to rely on other proteases for maturation, including TMPRSS2. Glycans near the cleavage site have raised questions about proteolytic processing and the consequences of variant-borne mutations. Here, we identify that sialic acid-containing O-linked glycans on Thr678 of SARS-CoV-2 spike influence furin and TMPRSS2 cleavage and posit O-linked glycosylation as a likely driving force for the emergence ofVOC mutations. We provide direct evidence that the glycosyltransferase GalNAc-T1 primes glycosylation at Thr678 in the living cell, an event that is suppressed by mutations in the VOCs Alpha, Delta, and Omicron. We found that the sole incorporation of N-acetylgalactosamine did not impact furin activity in synthetic O-glycopeptides, but the presence of sialic acid reduced the furin rate by up to 65{\%}. Similarly, O-glycosylation with a sialylated trisaccharide had a negative impact on TMPRSS2 cleavage. With a chemistry-centered approach, we substantiate O-glycosylation as a major determinant of spike maturation and propose disruption of O-glycosylation as a substantial driving force for VOC evolution.},
author = {Gonzalez-Rodriguez, Edgar and Zol-Hanlon, Mia and Bineva-Todd, Ganka and Marchesi, Andrea and Skehel, Mark and Mahoney, Keira E and Roustan, Chlo{\"{e}} and Borg, Annabel and Vagno, Lucia Di and Kj{\ae}r, Svend and Wrobel, Antoni G and Benton, Donald J and Nawrath, Philipp and Flitsch, Sabine L and Joshi, Dhira and Gonz{\'{a}}lez-Ram{\'{i}}rez, Andr{\'{e}}s Manuel and Wilkinson, Katalin A and Wilkinson, Robert J and Wall, Emma C and Hurtado-Guerrero, Ram{\'{o}}n and Malaker, Stacy A and Schumann, Benjamin},
doi = {10.1021/ACSCENTSCI.2C01349},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Gonzalez-Rodriguez et al. - 2023 - O-Linked sialoglycans modulate the proteolysis of SARS-CoV-2 spike and likely contribute to the mutat.pdf:pdf},
issn = {2374-7943},
journal = {ACS Central Science},
keywords = {OA,OA{\_}PMC,fund{\_}ack,genomics{\_}fund{\_}ack,original},
mendeley-tags = {OA,OA{\_}PMC,fund{\_}ack,genomics{\_}fund{\_}ack,original},
month = {feb},
pages = {10.1021/acscentsci.2c01349},
pmid = {36968546},
publisher = {American Chemical Society},
title = {{O-Linked sialoglycans modulate the proteolysis of SARS-CoV-2 spike and likely contribute to the mutational trajectory in variants of concern}},
url = {https://pubs.acs.org/doi/full/10.1021/acscentsci.2c01349},
year = {2023}
}

The emergence of a polybasic cleavage motif for the protease furin in SARS-CoV-2 spike has been established as a major factor for human viral transmission. The region N-terminal to that motif is extensively mutated in variants of concern (VOCs). Besides furin, spikes from these variants appear to rely on other proteases for maturation, including TMPRSS2. Glycans near the cleavage site have raised questions about proteolytic processing and the consequences of variant-borne mutations. Here, we identify that sialic acid-containing O-linked glycans on Thr678 of SARS-CoV-2 spike influence furin and TMPRSS2 cleavage and posit O-linked glycosylation as a likely driving force for the emergence ofVOC mutations. We provide direct evidence that the glycosyltransferase GalNAc-T1 primes glycosylation at Thr678 in the living cell, an event that is suppressed by mutations in the VOCs Alpha, Delta, and Omicron. We found that the sole incorporation of N-acetylgalactosamine did not impact furin activity in synthetic O-glycopeptides, but the presence of sialic acid reduced the furin rate by up to 65%. Similarly, O-glycosylation with a sialylated trisaccharide had a negative impact on TMPRSS2 cleavage. With a chemistry-centered approach, we substantiate O-glycosylation as a major determinant of spike maturation and propose disruption of O-glycosylation as a substantial driving force for VOC evolution.

@article{DuBruyn2023,
abstract = {Few studies from Africa have described the clinical impact of co-infections on SARS-CoV-2 infection. Here, we investigate the presentation and outcome of SARS-CoV-2 infection in an African setting of high HIV-1 and tuberculosis prevalence by an observational case cohort of SARS-CoV-2 patients. A comparator group of non SARS-CoV-2 participants is included. The study includes 104 adults with SARS-CoV-2 infection of whom 29.8{\%} are HIV-1 co-infected. Two or more co-morbidities are present in 57.7{\%} of participants, including HIV-1 (30{\%}) and active tuberculosis (14{\%}). Amongst patients dually infected by tuberculosis and SARS-CoV-2, clinical features can be typical of either SARS-CoV-2 or tuberculosis: lymphopenia is exacerbated, and some markers of inflammation (D-dimer and ferritin) are further elevated (p {\textless} 0.05). Amongst HIV-1 co-infected participants those with low CD4 percentage strata exhibit reduced total, but not neutralising, anti-SARS-CoV-2 antibodies. SARS-CoV-2 specific CD8 T cell responses are present in 35.8{\%} participants overall but undetectable in combined HIV-1 and tuberculosis. Death occurred in 30/104 (29{\%}) of all COVID-19 patients and in 6/15 (40{\%}) of patients with coincident SARS-CoV-2 and tuberculosis. This shows that in a high incidence setting, tuberculosis is a common co-morbidity in patients admitted to hospital with COVID-19. The immune response to SARS-CoV-2 is adversely affected by co-existent HIV-1 and tuberculosis. Here the authors describe outcomes of SARS-CoV-2 infection in an African setting of high HIV-1 and tuberculosis prevalence. They find that tuberculosis is a common co-morbidity in patients admitted to hospital with COVID-19 and that the immune response to SARS-CoV-2 is adversely affected by co-existent HIV-1 and tuberculosis.},
author = {{Du Bruyn}, Elsa and Stek, Cari and Daroowala, Remi and Said-Hartley, Qonita and Hsiao, Marvin and Schafer, Georgia and Goliath, Rene T and Abrahams, Fatima and Jackson, Amanda and Wasserman, Sean and Allwood, Brian W and Davis, Angharad G. and Lai, Rachel P.-J. and Coussens, Anna K and Wilkinson, Katalin A and de Vries, Jantina and Tiffin, Nicki and Cerrone, Maddalena and Ntusi, Ntobeko A B and HIATUS consortium and Riou, Catherine and Wilkinson, Robert J},
doi = {10.1038/s41467-022-35689-1},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Du Bruyn et al. - 2023 - Effects of tuberculosis andor HIV-1 infection on COVID-19 presentation and immune response in Africa.pdf:pdf},
issn = {2041-1723},
journal = {Nature Communications},
keywords = {Medical research,OA,OA{\_}PMC,Pathogenesis,fund{\_}ack,genomics{\_}fund{\_}ack,original},
mendeley-tags = {OA,OA{\_}PMC,fund{\_}ack,genomics{\_}fund{\_}ack,original},
month = {jan},
number = {1},
pages = {188},
pmid = {36635274},
publisher = {Nature Publishing Group},
title = {{Effects of tuberculosis and/or HIV-1 infection on COVID-19 presentation and immune response in Africa}},
url = {https://www.nature.com/articles/s41467-022-35689-1},
volume = {14},
year = {2023}
}

Few studies from Africa have described the clinical impact of co-infections on SARS-CoV-2 infection. Here, we investigate the presentation and outcome of SARS-CoV-2 infection in an African setting of high HIV-1 and tuberculosis prevalence by an observational case cohort of SARS-CoV-2 patients. A comparator group of non SARS-CoV-2 participants is included. The study includes 104 adults with SARS-CoV-2 infection of whom 29.8% are HIV-1 co-infected. Two or more co-morbidities are present in 57.7% of participants, including HIV-1 (30%) and active tuberculosis (14%). Amongst patients dually infected by tuberculosis and SARS-CoV-2, clinical features can be typical of either SARS-CoV-2 or tuberculosis: lymphopenia is exacerbated, and some markers of inflammation (D-dimer and ferritin) are further elevated (p \textless 0.05). Amongst HIV-1 co-infected participants those with low CD4 percentage strata exhibit reduced total, but not neutralising, anti-SARS-CoV-2 antibodies. SARS-CoV-2 specific CD8 T cell responses are present in 35.8% participants overall but undetectable in combined HIV-1 and tuberculosis. Death occurred in 30/104 (29%) of all COVID-19 patients and in 6/15 (40%) of patients with coincident SARS-CoV-2 and tuberculosis. This shows that in a high incidence setting, tuberculosis is a common co-morbidity in patients admitted to hospital with COVID-19. The immune response to SARS-CoV-2 is adversely affected by co-existent HIV-1 and tuberculosis. Here the authors describe outcomes of SARS-CoV-2 infection in an African setting of high HIV-1 and tuberculosis prevalence. They find that tuberculosis is a common co-morbidity in patients admitted to hospital with COVID-19 and that the immune response to SARS-CoV-2 is adversely affected by co-existent HIV-1 and tuberculosis.

@article{Moyo-Gwete2023,
abstract = {The impact of previous SARS-CoV-2 infection on the durability of Ad26.COV2.S vaccine-elicited responses, and the effect of homologous boosting has not been well explored. We followed a cohort of healthcare workers for 6 months after receiving the Ad26.COV2.S vaccine and a further one month after they received an Ad26.COV2.S booster dose. We assessed longitudinal spike-specific antibody and T cell responses in individuals who had never had SARS-CoV-2 infection, compared to those who were infected with either the D614G or Beta variants prior to vaccination. Antibody and T cell responses elicited by the primary dose were durable against several variants of concern over the 6 month follow-up period, regardless of infection history. However, at 6 months after first vaccination, antibody binding, neutralization and ADCC were as much as 33-fold higher in individuals with hybrid immunity compared to those with no prior infection. Antibody cross-reactivity profiles of the previously infected groups were similar at 6 months, unlike at earlier time points suggesting that the effect of immune imprinting diminishes by 6 months. Importantly, an Ad26.COV2.S booster dose increased the magnitude of the antibody response in individuals with no prior infection to similar levels as those with previous infection. The magnitude of spike T cell responses and proportion of T cell responders remained stable after homologous boosting, concomitant with a significant increase in long-lived early differentiated CD4 memory T cells. Thus, these data highlight that multiple antigen exposures, whether through infection and vaccination or vaccination alone, result in similar boosts after Ad26.COV2.S vaccination. {\#}{\#}{\#} Competing Interest Statement The authors have declared no competing interest. {\#}{\#}{\#} Funding Statement Research reported in this publication was supported by the South African Medical Research Council (SA MRC) with funds received from the South African Department of Science and Innovation (DSI), including grants 96825, SHIPNCD 76756 and DST/CON 0250/2012. This work was also supported by the Poliomyelitis Research Foundation (21/65) and the Wellcome Centre for Infectious Diseases Research in Africa (CIDRI-Africa), which is supported by core funding from Wellcome Trust (203135/Z/16/Z and 222574). We acknowledge funding from the Bill and Melinda Gates Foundation, through the Global Immunology and Immune Sequencing for Epidemic Response (GIISER) program. PLM is supported by the South African Research Chairs Initiative of the Department of Science and Innovation and National Research Foundation of South Africa (NRF 9834), the SA Medical Research Council SHIP program, the Centre for the AIDS Programme of Research in South Africa (CAPRISA). TMG is funded by a South African Medical Research Council Self-Initiated Research Grant. SIR is funded by the Poliomyelitis Research Foundation. WAB and CR are supported by the EDCTP2 programme of the European Union Horizon 2020 programme (TMA2017SF-1951-TB-SPEC to C.R. and TMA2016SF-1535-CaTCH-22 to WAB) and the Wellcome Trust (226137/Z/22/ Z). CR is supported by the National Institutes of Health (NIH) (R21AI148027). NABN acknowledges funding from the SA MRC, MRC UK, NRF and the Lily and Ernst Hausmann Trust. {\#}{\#}{\#} Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study was approved by the University of Cape Town Human Research Ethics Committee (Ethics number: HREC 190/2020 and 209/2020) and the University of the Witwatersrand Human Research Medical Ethics Committee (Ethics number: M210429). Written informed consent was obtained from all participants. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data are readily available upon request to the corresponding authors.},
author = {Moyo-Gwete, Thandeka and Richardson, Simone I and Keeton, Roanne and Hermanus, Tandile and Spencer, Holly and Manamela, Nelia P and Ayres, Frances and Makhado, Zanele and Motlou, Thopisang and Tincho, Marius B and Benede, Ntombi and Ngomti, Amkele and Baguma, Richard and Chauke, Masego V and Mennen, Mathilda and Adriaanse, Marguerite and Skelem, Sango and Goga, Ameena and Garrett, Nigel and Bekker, Linda-Gail and Gray, Glenda and Ntusi, Ntobeko A B and Riou, Catherine and Burgers, Wendy A and Moore, Penny L},
doi = {10.1101/2023.03.15.23287288},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Moyo-Gwete et al. - 2023 - Homologous Ad26.COV2.S vaccination results in reduced boosting of humoral responses in hybrid immunity, but e.pdf:pdf},
journal = {medRxiv},
keywords = {ADCC,Ad26COV2S vaccine,OA,SARS-CoV-2,T cells,antibodies,fund{\_}ack,genomics{\_}fund{\_}ack,hybrid immunity,memory differentiation,neutralization,original},
mendeley-tags = {OA,fund{\_}ack,genomics{\_}fund{\_}ack,original},
month = {mar},
pages = {2023.03.15.23287288},
publisher = {Cold Spring Harbor Laboratory Press},
title = {{Homologous Ad26.COV2.S vaccination results in reduced boosting of humoral responses in hybrid immunity, but elicits antibodies of similar magnitude regardless of prior infection}},
url = {https://www.medrxiv.org/content/10.1101/2023.03.15.23287288v1 https://www.medrxiv.org/content/10.1101/2023.03.15.23287288v1.abstract},
volume = {10},
year = {2023}
}

The impact of previous SARS-CoV-2 infection on the durability of Ad26.COV2.S vaccine-elicited responses, and the effect of homologous boosting has not been well explored. We followed a cohort of healthcare workers for 6 months after receiving the Ad26.COV2.S vaccine and a further one month after they received an Ad26.COV2.S booster dose. We assessed longitudinal spike-specific antibody and T cell responses in individuals who had never had SARS-CoV-2 infection, compared to those who were infected with either the D614G or Beta variants prior to vaccination. Antibody and T cell responses elicited by the primary dose were durable against several variants of concern over the 6 month follow-up period, regardless of infection history. However, at 6 months after first vaccination, antibody binding, neutralization and ADCC were as much as 33-fold higher in individuals with hybrid immunity compared to those with no prior infection. Antibody cross-reactivity profiles of the previously infected groups were similar at 6 months, unlike at earlier time points suggesting that the effect of immune imprinting diminishes by 6 months. Importantly, an Ad26.COV2.S booster dose increased the magnitude of the antibody response in individuals with no prior infection to similar levels as those with previous infection. The magnitude of spike T cell responses and proportion of T cell responders remained stable after homologous boosting, concomitant with a significant increase in long-lived early differentiated CD4 memory T cells. Thus, these data highlight that multiple antigen exposures, whether through infection and vaccination or vaccination alone, result in similar boosts after Ad26.COV2.S vaccination. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement Research reported in this publication was supported by the South African Medical Research Council (SA MRC) with funds received from the South African Department of Science and Innovation (DSI), including grants 96825, SHIPNCD 76756 and DST/CON 0250/2012. This work was also supported by the Poliomyelitis Research Foundation (21/65) and the Wellcome Centre for Infectious Diseases Research in Africa (CIDRI-Africa), which is supported by core funding from Wellcome Trust (203135/Z/16/Z and 222574). We acknowledge funding from the Bill and Melinda Gates Foundation, through the Global Immunology and Immune Sequencing for Epidemic Response (GIISER) program. PLM is supported by the South African Research Chairs Initiative of the Department of Science and Innovation and National Research Foundation of South Africa (NRF 9834), the SA Medical Research Council SHIP program, the Centre for the AIDS Programme of Research in South Africa (CAPRISA). TMG is funded by a South African Medical Research Council Self-Initiated Research Grant. SIR is funded by the Poliomyelitis Research Foundation. WAB and CR are supported by the EDCTP2 programme of the European Union Horizon 2020 programme (TMA2017SF-1951-TB-SPEC to C.R. and TMA2016SF-1535-CaTCH-22 to WAB) and the Wellcome Trust (226137/Z/22/ Z). CR is supported by the National Institutes of Health (NIH) (R21AI148027). NABN acknowledges funding from the SA MRC, MRC UK, NRF and the Lily and Ernst Hausmann Trust. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study was approved by the University of Cape Town Human Research Ethics Committee (Ethics number: HREC 190/2020 and 209/2020) and the University of the Witwatersrand Human Research Medical Ethics Committee (Ethics number: M210429). Written informed consent was obtained from all participants. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data are readily available upon request to the corresponding authors.

@article{Nesamari2023,
abstract = {The COVID-19 post-pandemic period is characterised by infection waves of uncertain size (due to low rates of SARS-CoV-2 testing and notification), as well as limited uptake or global access to updated variant vaccines. Ongoing SARS-CoV-2 evolution has given rise to recombinant Omicron lineages that dominate globally (XBB.1), as well as the emergence of hypermutated variants (BA.2.86). In this context, durable and cross-reactive T-cell immune memory is critical for continued protection against severe COVID-19. We examined T-cell responses to SARS-CoV-2 approximately 1.5 years since Omicron first emerged. We describe sustained CD4+ and CD8+ spike-specific T-cell memory responses in healthcare workers in South Africa (n=39), most of whom had received 2 doses of Ad26.CoV2.S (Johnson {\&} Johnson/Janssen) vaccine and experienced at least one SARS-CoV-2 infection. Spike-specific T cells were highly cross-reactive with all Omicron variants tested, including BA.2.86. Abundant non-spike (nucleocapsid and membrane)-specific T cells were detectable in most participants, augmenting the total T-cell resources available for protection. The bulk of SARS-CoV-2-specific T-cell responses had an early-differentiated phenotype, explaining their persistent nature. Thus, hybrid immunity leads to the accumulation of spike and non-spike T cells evident 3.5 years after the start of the pandemic, with preserved recognition of highly mutated SARS-CoV-2 variants. Long-term T-cell immune memory is likely to provide continued protection against severe outcomes of COVID-19. {\#}{\#}{\#} Competing Interest Statement Alex Sette is a consultant for AstraZeneca Pharmaceuticals, Calyptus Pharmaceuticals, Inc, Darwin Health, EmerVax, EUROIMMUN, F. Hoffman-La Roche Ltd, Fortress Biotech, Gilead Sciences, Granite bio., Gritstone Oncology, Guggenheim Securities, Moderna, Pfizer, RiverVest Venture Partners, and Turnstone Biologics. Alba Grifoni is a consultant for Pfizer. LJI has filed for patent protection for various aspects of T cell epitope and vaccine design work. All other authors declare no competing interests. {\#}{\#}{\#} Funding Statement Wellcome Trust (226137/Z/22/Z) South African Medical Research Council (SA-MRC) with funds received from the South African Department of Science and Innovation (DSI) Bill and Melinda Gates Foundation (INV-046743) Poliomyelitis Research Foundation (21/65) Wellcome Centre for Infectious Diseases Research in Africa (CIDRI-Africa) which is supported by core funding from the Wellcome Trust (203135/Z/16/Z and 222754) W.A.B. and C.R. are supported by the EDCTP2 program of the European Unions Horizon 2020 program (TMA2016SF-1535-CaTCH-22 to W.A.B and TMA2017SF-1951-TB-SPEC to C.R.) R.N. is supported by the Harry Crossley Foundation N.A.B.N. acknowledges funding from the SA-MRC, MRC UK, NRF, and the Lily and Ernst Hausmann Trust This project has been funded in part with Federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under Contract No. 75N93021C00016 to A.G. and Contract No. 75N93019C00065 to A.S. {\#}{\#}{\#} Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study was approved by the University of Cape Town Human Research Ethics Committee (HREC 190/2020 and 291/2020), and written informed consent was obtained from all participants. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data reported in this paper will be shared by the lead contacts upon request. This paper does not report original code. Any additional information required to reanalyze the data reported in this paper is available from the lead contacts upon request.},
author = {Nesamari, Rofhiwa and Omondi, Millicent A and H{\"{o}}ft, Maxine A and Ngomti, Amkele and Baguma, Richard and Nkayi, Anathi A and Besethi, Asiphe S and Magugu, Siyabulela F J and Mosala, Paballo and Walters, Avril and Clark, Gesina M and Mennen, Mathilda and Skelem, Sango and Adriaanse, Marguerite and Grifoni, Alba and Sette, Alessandro and Keeton, Roanne S and Ntusi, Ntobeko A B and Riou, Catherine and Burgers, Wendy A},
doi = {10.1101/2023.10.28.23297714},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Nesamari et al. - 2023 - Post-pandemic memory T-cell response to SARS-CoV-2 is durable, broadly targeted and cross-reactive to hypermuta.pdf:pdf},
journal = {medRxiv},
keywords = {OA,fund{\_}ack,genomics{\_}fund{\_}ack,original},
mendeley-tags = {OA,fund{\_}ack,genomics{\_}fund{\_}ack,original},
month = {oct},
pages = {2023.10.28.23297714},
publisher = {Cold Spring Harbor Laboratory Press},
title = {{Post-pandemic memory T-cell response to SARS-CoV-2 is durable, broadly targeted and cross-reactive to hypermutated BA.2.86}},
url = {https://www.medrxiv.org/content/10.1101/2023.10.28.23297714v1 https://www.medrxiv.org/content/10.1101/2023.10.28.23297714v1.abstract},
year = {2023}
}

The COVID-19 post-pandemic period is characterised by infection waves of uncertain size (due to low rates of SARS-CoV-2 testing and notification), as well as limited uptake or global access to updated variant vaccines. Ongoing SARS-CoV-2 evolution has given rise to recombinant Omicron lineages that dominate globally (XBB.1), as well as the emergence of hypermutated variants (BA.2.86). In this context, durable and cross-reactive T-cell immune memory is critical for continued protection against severe COVID-19. We examined T-cell responses to SARS-CoV-2 approximately 1.5 years since Omicron first emerged. We describe sustained CD4+ and CD8+ spike-specific T-cell memory responses in healthcare workers in South Africa (n=39), most of whom had received 2 doses of Ad26.CoV2.S (Johnson & Johnson/Janssen) vaccine and experienced at least one SARS-CoV-2 infection. Spike-specific T cells were highly cross-reactive with all Omicron variants tested, including BA.2.86. Abundant non-spike (nucleocapsid and membrane)-specific T cells were detectable in most participants, augmenting the total T-cell resources available for protection. The bulk of SARS-CoV-2-specific T-cell responses had an early-differentiated phenotype, explaining their persistent nature. Thus, hybrid immunity leads to the accumulation of spike and non-spike T cells evident 3.5 years after the start of the pandemic, with preserved recognition of highly mutated SARS-CoV-2 variants. Long-term T-cell immune memory is likely to provide continued protection against severe outcomes of COVID-19. ### Competing Interest Statement Alex Sette is a consultant for AstraZeneca Pharmaceuticals, Calyptus Pharmaceuticals, Inc, Darwin Health, EmerVax, EUROIMMUN, F. Hoffman-La Roche Ltd, Fortress Biotech, Gilead Sciences, Granite bio., Gritstone Oncology, Guggenheim Securities, Moderna, Pfizer, RiverVest Venture Partners, and Turnstone Biologics. Alba Grifoni is a consultant for Pfizer. LJI has filed for patent protection for various aspects of T cell epitope and vaccine design work. All other authors declare no competing interests. ### Funding Statement Wellcome Trust (226137/Z/22/Z) South African Medical Research Council (SA-MRC) with funds received from the South African Department of Science and Innovation (DSI) Bill and Melinda Gates Foundation (INV-046743) Poliomyelitis Research Foundation (21/65) Wellcome Centre for Infectious Diseases Research in Africa (CIDRI-Africa) which is supported by core funding from the Wellcome Trust (203135/Z/16/Z and 222754) W.A.B. and C.R. are supported by the EDCTP2 program of the European Unions Horizon 2020 program (TMA2016SF-1535-CaTCH-22 to W.A.B and TMA2017SF-1951-TB-SPEC to C.R.) R.N. is supported by the Harry Crossley Foundation N.A.B.N. acknowledges funding from the SA-MRC, MRC UK, NRF, and the Lily and Ernst Hausmann Trust This project has been funded in part with Federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under Contract No. 75N93021C00016 to A.G. and Contract No. 75N93019C00065 to A.S. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study was approved by the University of Cape Town Human Research Ethics Committee (HREC 190/2020 and 291/2020), and written informed consent was obtained from all participants. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data reported in this paper will be shared by the lead contacts upon request. This paper does not report original code. Any additional information required to reanalyze the data reported in this paper is available from the lead contacts upon request.

@article{Riou2023a,
abstract = {Background. We report the safety and immunogenicity of fractional and full dose Ad26.COV2.S and BNT162b2 in an open label phase 2 trial of participants previously vaccinated with a single dose of Ad26.COV2.S, with 91.4{\%} showing evidence of previous SARS-CoV-2 infection. Methods. A total of 286 adults (with or without HIV) were enrolled {\textgreater}4 months after an Ad26.COV2.S prime and randomized 1:1:1:1 to receive either a full or half-dose booster of Ad26.COV2.S or BNT162b2 vaccine. B cell responses (binding, neutralization and antibody dependent cellular cytotoxicity-ADCC), and spike-specific T-cell responses were evaluated at baseline, 2, 12 and 24 weeks post-boost. Antibody and T-cell immunity targeting the Ad26 vector was also evaluated. Results. No vaccine-associated serious adverse events were recorded. The full- and half-dose BNT162b2 boosted anti-SARS-CoV-2 binding antibody levels (3.9- and 4.5-fold, respectively) and neutralizing antibody levels (4.4- and 10-fold). Binding and neutralizing antibodies following half-dose Ad26.COV2.S were not significantly boosted. Full-dose Ad26.COV2.S did not boost binding antibodies but slightly enhanced neutralizing antibodies (2.1-fold). ADCC was marginally increased only after a full-dose BNT162b2. T-cell responses followed a similar pattern to neutralizing antibodies. Six months post-boost, antibody and T-cell responses had waned to baseline levels. While we detected strong anti-vector immunity, there was no correlation between anti-vector immunity in Ad26.COV2.S recipients and spike-specific neutralizing antibody or T-cell responses post-Ad26.COV2.S boosting. Conclusion. In the context of hybrid immunity, boosting with heterologous full- or half-dose BNT162b2 mRNA vaccine demonstrated superior immunogenicity 2 weeks post-vaccination compared to homologous Ad26.COV2.S, though rapid waning occurred by 12 weeks post-boost. Trial Registration: South African National Clinical Trial Registry (SANCR): DOH-27-012022-7841; Funding: South African Medical Research Council (SAMRC) and South African Department of Health (SA DoH). {\#}{\#}{\#} Competing Interest Statement I have read the journal's policy and the authors of this manuscript have the following competing interests: A.Se. is a consultant for AstraZeneca Pharmaceuticals, Calyptus Pharmaceuticals, Inc, Darwin Health, EmerVax, EUROIMMUN, F. Hoffman-La Roche Ltd, Fortress Biotech, Gilead Sciences, Granite bio., Gritstone Oncology, Guggenheim Securities, Moderna, Pfizer, RiverVest Venture Partners, and Turnstone Biologics. A.G. is a consultant for Pfizer. LJI has filed for patent protection for various aspects of T cell epitope and vaccine design work. All other authors declare no competing interests {\#}{\#}{\#} Clinical Trial The study has been registered to the South African National Clinical Trial Registry (SANCR): DOH-27-012022-7841. {\#}{\#}{\#} Funding Statement yes This study was funded by the South African Medical research Council (SAMRC), the Bill and Melinda Gates Foundation, through the Global Immunology and Immune Sequencing for Epidemic Response (GIISER) program (INV-030570) and the Wellcome Trust (226137/Z/22/Z). P.L.M is supported by the SAMRC (96833) and is an Department of Science and Innovation-National Research Foundation South African Research Chair (98341). A.Si. is supported by the Bill and Melinda Gates foundation (INV-046743) and the SAMRC (D2112300-01). W.A.B. is supported by the EDCTP2 program of the European Union's Horizon 2020 programme (TMA2016SF-1535-CaTCH-22) and the EU-Africa Concerted Action on SARS-CoV-2 Virus Variant and Immunological Surveillance (COVICIS), funded through the EU's Horizon Europe Research and Innovation Programme (101046041). C.R. is supported by the EDCTP2 program (TMA2017SF-1951-TB-SPEC). This project has also been funded in part by the National Institute of Allergy and Infectious Diseases, NIH, Department of Health and Human Services, under Contract No. 75N93021C00016 to A.G. and 75N93019C00065 to A.Se. The Wits RHI site received grant funding from Janssen to conduct the following clinical trials: Ensemble study (3UM1 AI068614-14SI), the Sisonke 1 study (96833), the Sherpa Study (96867) as well as Pfizer for the Pfizer C4591015 study (C4591015), Horizon 1 (VAC31518COV2004) and Horizon 2 (VAC31518COV3006). For the purposes of open access, the authors have applied a CC-BY public copyright license to any author-accepted version. {\#}{\#}{\#} Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This study has been approved by the South African Health Products Regulatory Authority (SAHPRA) and all site-specific Human Research Ethics Committees (HREC numbers: Wits 211001B, UKZN: BREC/00003487/2021, UCT 680/2021 SAHPRA: 20210423). All participants provided written informed consent. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data underlying the findings described in this manuscript may be obtained from the lead authors upon request.},
author = {Riou, Catherine and Bhiman, Jinal N and Ganga, Yashica and Sawry, Shobna and Ayres, Frances and Baguma, Richard and Balla, Sashkia R and Benede, Ntombi and Bernstein, Mallory and Besethi, Asiphe S and Cele, Sandile and Crowther, Carol and Dhar, Mrinmayee and Geyer, Sohair and Gill, Katherine and Grifoni, Alba and Hermanus, Tandile and Kaldine, Haajira and Keeton, Roanne S and Kgagudi, Prudence and Khan, Khadija and Lazarus, Erica and Roux, Jean Le and Lustig, Gila and Madzivhandila, Mashudu and Magugu, Siyabulela FJ and Makhado, Zanele and Manamela, Nelia P and Mkhize, Qiniso and Mosala, Paballo and Motlou, Thopisang P and Mutavhatsindi, Hygon and Mzindle, Nonkululeko B and Nana, Anusha and Nesamari, Rofhiwa and Ngomti, Amkele and Nkayi, Anathi A and Nkosi, Thandeka P and Omondi, Millicent A and Panchia, Ravindre and Patel, Faeezah and Sette, Alessandro and Singh, Upasna and van Graan, Strauss and Venter, Elizabeth M. and Walters, Avril and Moyo-Gwete, Thandeka and Richardson, Simone I. and Garrett, Nigel and Rees, Helen and Bekker, Linda-Gail and Gray, Glenda and Burgers, Wendy A. and Sigal, Alex and Moore, Penny L and Fairlie, Lee},
doi = {10.1101/2023.11.20.23298785},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Riou et al. - 2023 - Safety and immunogenicity of booster vaccination and fractional dosing with Ad26.COV2.S or BNT162b2 in Ad26.COV2.S-.pdf:pdf},
journal = {medRxiv},
keywords = {OA,OA{\_}PMC,fund{\_}not{\_}ack,original},
mendeley-tags = {OA,OA{\_}PMC,fund{\_}not{\_}ack,original},
month = {nov},
pages = {2023.11.20.23298785},
pmid = {38045321},
publisher = {Cold Spring Harbor Laboratory Press},
title = {{Safety and immunogenicity of booster vaccination and fractional dosing with Ad26.COV2.S or BNT162b2 in Ad26.COV2.S-vaccinated participants}},
url = {https://www.medrxiv.org/content/10.1101/2023.11.20.23298785v1 https://www.medrxiv.org/content/10.1101/2023.11.20.23298785v1.abstract},
year = {2023}
}

Background. We report the safety and immunogenicity of fractional and full dose Ad26.COV2.S and BNT162b2 in an open label phase 2 trial of participants previously vaccinated with a single dose of Ad26.COV2.S, with 91.4% showing evidence of previous SARS-CoV-2 infection. Methods. A total of 286 adults (with or without HIV) were enrolled \textgreater4 months after an Ad26.COV2.S prime and randomized 1:1:1:1 to receive either a full or half-dose booster of Ad26.COV2.S or BNT162b2 vaccine. B cell responses (binding, neutralization and antibody dependent cellular cytotoxicity-ADCC), and spike-specific T-cell responses were evaluated at baseline, 2, 12 and 24 weeks post-boost. Antibody and T-cell immunity targeting the Ad26 vector was also evaluated. Results. No vaccine-associated serious adverse events were recorded. The full- and half-dose BNT162b2 boosted anti-SARS-CoV-2 binding antibody levels (3.9- and 4.5-fold, respectively) and neutralizing antibody levels (4.4- and 10-fold). Binding and neutralizing antibodies following half-dose Ad26.COV2.S were not significantly boosted. Full-dose Ad26.COV2.S did not boost binding antibodies but slightly enhanced neutralizing antibodies (2.1-fold). ADCC was marginally increased only after a full-dose BNT162b2. T-cell responses followed a similar pattern to neutralizing antibodies. Six months post-boost, antibody and T-cell responses had waned to baseline levels. While we detected strong anti-vector immunity, there was no correlation between anti-vector immunity in Ad26.COV2.S recipients and spike-specific neutralizing antibody or T-cell responses post-Ad26.COV2.S boosting. Conclusion. In the context of hybrid immunity, boosting with heterologous full- or half-dose BNT162b2 mRNA vaccine demonstrated superior immunogenicity 2 weeks post-vaccination compared to homologous Ad26.COV2.S, though rapid waning occurred by 12 weeks post-boost. Trial Registration: South African National Clinical Trial Registry (SANCR): DOH-27-012022-7841; Funding: South African Medical Research Council (SAMRC) and South African Department of Health (SA DoH). ### Competing Interest Statement I have read the journal's policy and the authors of this manuscript have the following competing interests: A.Se. is a consultant for AstraZeneca Pharmaceuticals, Calyptus Pharmaceuticals, Inc, Darwin Health, EmerVax, EUROIMMUN, F. Hoffman-La Roche Ltd, Fortress Biotech, Gilead Sciences, Granite bio., Gritstone Oncology, Guggenheim Securities, Moderna, Pfizer, RiverVest Venture Partners, and Turnstone Biologics. A.G. is a consultant for Pfizer. LJI has filed for patent protection for various aspects of T cell epitope and vaccine design work. All other authors declare no competing interests ### Clinical Trial The study has been registered to the South African National Clinical Trial Registry (SANCR): DOH-27-012022-7841. ### Funding Statement yes This study was funded by the South African Medical research Council (SAMRC), the Bill and Melinda Gates Foundation, through the Global Immunology and Immune Sequencing for Epidemic Response (GIISER) program (INV-030570) and the Wellcome Trust (226137/Z/22/Z). P.L.M is supported by the SAMRC (96833) and is an Department of Science and Innovation-National Research Foundation South African Research Chair (98341). A.Si. is supported by the Bill and Melinda Gates foundation (INV-046743) and the SAMRC (D2112300-01). W.A.B. is supported by the EDCTP2 program of the European Union's Horizon 2020 programme (TMA2016SF-1535-CaTCH-22) and the EU-Africa Concerted Action on SARS-CoV-2 Virus Variant and Immunological Surveillance (COVICIS), funded through the EU's Horizon Europe Research and Innovation Programme (101046041). C.R. is supported by the EDCTP2 program (TMA2017SF-1951-TB-SPEC). This project has also been funded in part by the National Institute of Allergy and Infectious Diseases, NIH, Department of Health and Human Services, under Contract No. 75N93021C00016 to A.G. and 75N93019C00065 to A.Se. The Wits RHI site received grant funding from Janssen to conduct the following clinical trials: Ensemble study (3UM1 AI068614-14SI), the Sisonke 1 study (96833), the Sherpa Study (96867) as well as Pfizer for the Pfizer C4591015 study (C4591015), Horizon 1 (VAC31518COV2004) and Horizon 2 (VAC31518COV3006). For the purposes of open access, the authors have applied a CC-BY public copyright license to any author-accepted version. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This study has been approved by the South African Health Products Regulatory Authority (SAHPRA) and all site-specific Human Research Ethics Committees (HREC numbers: Wits 211001B, UKZN: BREC/00003487/2021, UCT 680/2021 SAHPRA: 20210423). All participants provided written informed consent. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data underlying the findings described in this manuscript may be obtained from the lead authors upon request.

@article{Kassanjee2023,
abstract = {Introduction: While a large proportion of people with HIV (PWH) have experienced SARS-CoV-2 infections, there is uncertainty about the role of HIV disease severity on COVID-19 outcomes, especially in lower-income settings. We studied the association of mortality with characteristics of HIV severity and management, and vaccination, among adult PWH. Methods: We analysed observational cohort data on all PWH aged ≥15 years experiencing a diagnosed SARS-CoV-2 infection (until March 2022), who accessed public sector healthcare in the Western Cape province of South Africa. Logistic regression was used to study the association of mortality with evidence of antiretroviral therapy (ART) collection, time since first HIV evidence, CD4 cell count, viral load (among those with evidence of ART collection) and COVID-19 vaccination, adjusting for demographic characteristics, comorbidities, admission pressure, location and time period. Results: Mortality occurred in 5.7{\%} (95{\%} CI: 5.3,6.0) of 17,831 first-diagnosed infections. Higher mortality was associated with lower recent CD4, no evidence of ART collection, high or unknown recent viral load and recent first HIV evidence, differentially by age. Vaccination was protective. The burden of comorbidities was high, and tuberculosis (especially more recent episodes of tuberculosis), chronic kidney disease, diabetes and hypertension were associated with higher mortality, more strongly in younger adults. Conclusions: Mortality was strongly associated with suboptimal HIV control, and the prevalence of these risk factors increased in later COVID-19 waves. It remains a public health priority to ensure PWH are on suppressive ART and vaccinated , and manage any disruptions in care that occurred during the pandemic. The diagnosis and management of comorbidi-ties, including for tuberculosis, should be optimized.},
author = {Kassanjee, Reshma and Davies, Mary-Ann and Ngwenya, Olina and Osei-Yeboah, Richard and Jacobs, Theuns and Morden, Erna and Timmerman, Venessa and Britz, Stefan and Mendelson, Marc and Taljaard, Jantjie and Riou, Julien and Boulle, Andrew and Tiffin, Nicki and Zinyakatira, Nesbert},
doi = {10.1002/JIA2.26104},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Kassanjee et al. - 2023 - COVID-19 among adults living with HIV correlates of mortality among public sector healthcare users in Western.pdf:pdf},
issn = {1758-2652},
journal = {Journal of the International AIDS Society},
keywords = {19,2,CD4 count,COVID,CoV,HIV,OA,OA{\_}PMC,SARS,South Africa,fund{\_}ack,genomics{\_}fund{\_}ack,mortality,original},
mendeley-tags = {OA,OA{\_}PMC,fund{\_}ack,genomics{\_}fund{\_}ack,original},
month = {jun},
number = {6},
pages = {e26104},
pmid = {37339333},
publisher = {John Wiley {\&} Sons, Ltd},
title = {{COVID-19 among adults living with HIV: correlates of mortality among public sector healthcare users in Western Cape, South Africa}},
url = {https://onlinelibrary.wiley.com/doi/full/10.1002/jia2.26104 https://onlinelibrary.wiley.com/doi/abs/10.1002/jia2.26104 https://onlinelibrary.wiley.com/doi/10.1002/jia2.26104},
volume = {26},
year = {2023}
}

Introduction: While a large proportion of people with HIV (PWH) have experienced SARS-CoV-2 infections, there is uncertainty about the role of HIV disease severity on COVID-19 outcomes, especially in lower-income settings. We studied the association of mortality with characteristics of HIV severity and management, and vaccination, among adult PWH. Methods: We analysed observational cohort data on all PWH aged ≥15 years experiencing a diagnosed SARS-CoV-2 infection (until March 2022), who accessed public sector healthcare in the Western Cape province of South Africa. Logistic regression was used to study the association of mortality with evidence of antiretroviral therapy (ART) collection, time since first HIV evidence, CD4 cell count, viral load (among those with evidence of ART collection) and COVID-19 vaccination, adjusting for demographic characteristics, comorbidities, admission pressure, location and time period. Results: Mortality occurred in 5.7% (95% CI: 5.3,6.0) of 17,831 first-diagnosed infections. Higher mortality was associated with lower recent CD4, no evidence of ART collection, high or unknown recent viral load and recent first HIV evidence, differentially by age. Vaccination was protective. The burden of comorbidities was high, and tuberculosis (especially more recent episodes of tuberculosis), chronic kidney disease, diabetes and hypertension were associated with higher mortality, more strongly in younger adults. Conclusions: Mortality was strongly associated with suboptimal HIV control, and the prevalence of these risk factors increased in later COVID-19 waves. It remains a public health priority to ensure PWH are on suppressive ART and vaccinated , and manage any disruptions in care that occurred during the pandemic. The diagnosis and management of comorbidi-ties, including for tuberculosis, should be optimized.

@article{Benede2023,
abstract = {SUMMARY SARS-CoV-2 infection in children typically results in asymptomatic or mild disease. There is a paucity of studies on antiviral immunity in African children. We investigated SARS-CoV-2-specific T cell responses in 71 unvaccinated asymptomatic South African children who were seropositive or seronegative for SARS-CoV-2. SARS-CoV-2-specific CD4+ T cell responses were detectable in 83{\%} of seropositive and 60{\%} of seronegative children. Although the magnitude of the CD4+ T cell response did not differ significantly between the two groups, their functional profiles were distinct, with SARS-CoV-2 seropositive children exhibiting a higher proportion of polyfunctional T cells compared to their seronegative counterparts. The frequency of SARS-CoV-2-specific CD4+ T cells in seronegative children was associated with the endemic human coronavirus (HCoV) HKU1 IgG response. Overall, the presence of SARS-CoV-2-responding T cells in seronegative children may result from cross-reactivity to endemic coronaviruses and could contribute to the relative protection from disease observed in SARS-CoV-2-infected children. Key words: SARS-CoV-2, Children, IgG responses, T cell response, Polyfunctional profile, endemic HCoV {\#}{\#}{\#} Competing Interest Statement The authors have declared no competing interest. {\#}{\#}{\#} Funding Statement This work is supported by the South African Medical Research Council (SA-MRC) with funds received from the South African Department of Science and Innovation (DSI), (grants 96825, SHIPNCD 76756, and DST/CON 0250/2012), the Poliomyelitis Research Foundation (21/65) and the Wellcome Centre for Infectious Diseases Research in Africa (CIDRI-Africa), which is supported by core funding from the Wellcome Trust (203135/Z/16/Z and 222754). SA-MRC to R.S.K. UK NIHR GECO award (GEC111 to H.J.Z), the Bill {\&} Melinda Gates Foundation, USA (grants OPP1017641, OPP1017579 to H.J.Z). P.L.M. is supported by the South African Research Chairs Initiative of the Department of Science and Innovation and National Research Foundation of South Africa (NRF 9834), the SA Medical Research Council SHIP programme and the Centre for the AIDS Programme of Research in South Africa (CAPRISA). C.R. is supported by the EDCTP2 program of the European Unions Horizon 2020 programme (TMA2017SF-1951-TB-SPEC), the Wellcome Trust (226137/Z/22/Z) and the National Institutes of Health (NIH) (R21AI148027). W.A.B. is supported by the EDCTP2 program of the European Unions Horizon 2020 programme (TMA2016SF-1535-CaTCH-22), the Wellcome Trust (226137/Z/22/Z) and the EU-Africa Concerted Action on SARS-CoV-2 Virus Variant and Immunological Surveillance (COVICIS), funded through the EUs Horizon Europe Research and Innovation Programme (101046041). H.J.Z is supported by the SA-MRC. L.J.Z. is funded by the South African Medical Research Council (SAMRC) through its Division of Research Capacity Development under the Mid-Career Scientist Programme from funding received from the South African National Treasury. The content hereof is the sole responsibility of the authors and do not necessarily represent the official views of the SAMRC. L.J.Z also receives support from the National Research Foundation of South Africa (NRFSA), as well as the UK Medical Research Council (MRC) and the UK Department for International Development (DFID) under the MRC/DFID Concordat agreement, via the African Research Leader Award (MR/S005242/1). {\#}{\#}{\#} Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The University of Cape Town Human Ethics Committee gave ethical approval for this work (HREC 599/2020, 401/2009, 190/2020 and 209/2020). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors},
author = {Benede, Ntombi S.B. and Tincho, Marius B and Walters, Avril and Subbiah, Vennesa and Ngomti, Amkele and Baguma, Richard and Butters, Claire and Mennen, Mathilda and Skelem, Sango and Adriaanse, Marguerite and van Graan, Strauss and Balla, Sashkia R. and Moyo-Gwete, Thandeka and Moore, Penny L. and Botha, Maresa and Workman, Lesley and Zar, Heather J. and Ntusi, Ntobeko A. B. and Z{\"{u}}hlke, Liesl and Webb, Kate and Riou, Catherine and Burgers, Wendy A and Keeton, Roanne S},
doi = {10.1101/2023.05.16.23290059},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Benede et al. - 2023 - Distinct T cell functional profiles in SARS-CoV-2 seropositive and seronegative children associated with endemic.pdf:pdf},
journal = {medRxiv},
keywords = {OA,fund{\_}ack,genomics{\_}fund{\_}ack,original},
mendeley-tags = {OA,fund{\_}ack,genomics{\_}fund{\_}ack,original},
month = {may},
pages = {2023.05.16.23290059},
publisher = {Cold Spring Harbor Laboratory Press},
title = {{Distinct T cell functional profiles in SARS-CoV-2 seropositive and seronegative children associated with endemic human coronavirus cross-reactivity}},
url = {https://www.medrxiv.org/content/10.1101/2023.05.16.23290059v1 https://www.medrxiv.org/content/10.1101/2023.05.16.23290059v1.abstract},
year = {2023}
}

SUMMARY SARS-CoV-2 infection in children typically results in asymptomatic or mild disease. There is a paucity of studies on antiviral immunity in African children. We investigated SARS-CoV-2-specific T cell responses in 71 unvaccinated asymptomatic South African children who were seropositive or seronegative for SARS-CoV-2. SARS-CoV-2-specific CD4+ T cell responses were detectable in 83% of seropositive and 60% of seronegative children. Although the magnitude of the CD4+ T cell response did not differ significantly between the two groups, their functional profiles were distinct, with SARS-CoV-2 seropositive children exhibiting a higher proportion of polyfunctional T cells compared to their seronegative counterparts. The frequency of SARS-CoV-2-specific CD4+ T cells in seronegative children was associated with the endemic human coronavirus (HCoV) HKU1 IgG response. Overall, the presence of SARS-CoV-2-responding T cells in seronegative children may result from cross-reactivity to endemic coronaviruses and could contribute to the relative protection from disease observed in SARS-CoV-2-infected children. Key words: SARS-CoV-2, Children, IgG responses, T cell response, Polyfunctional profile, endemic HCoV ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work is supported by the South African Medical Research Council (SA-MRC) with funds received from the South African Department of Science and Innovation (DSI), (grants 96825, SHIPNCD 76756, and DST/CON 0250/2012), the Poliomyelitis Research Foundation (21/65) and the Wellcome Centre for Infectious Diseases Research in Africa (CIDRI-Africa), which is supported by core funding from the Wellcome Trust (203135/Z/16/Z and 222754). SA-MRC to R.S.K. UK NIHR GECO award (GEC111 to H.J.Z), the Bill & Melinda Gates Foundation, USA (grants OPP1017641, OPP1017579 to H.J.Z). P.L.M. is supported by the South African Research Chairs Initiative of the Department of Science and Innovation and National Research Foundation of South Africa (NRF 9834), the SA Medical Research Council SHIP programme and the Centre for the AIDS Programme of Research in South Africa (CAPRISA). C.R. is supported by the EDCTP2 program of the European Unions Horizon 2020 programme (TMA2017SF-1951-TB-SPEC), the Wellcome Trust (226137/Z/22/Z) and the National Institutes of Health (NIH) (R21AI148027). W.A.B. is supported by the EDCTP2 program of the European Unions Horizon 2020 programme (TMA2016SF-1535-CaTCH-22), the Wellcome Trust (226137/Z/22/Z) and the EU-Africa Concerted Action on SARS-CoV-2 Virus Variant and Immunological Surveillance (COVICIS), funded through the EUs Horizon Europe Research and Innovation Programme (101046041). H.J.Z is supported by the SA-MRC. L.J.Z. is funded by the South African Medical Research Council (SAMRC) through its Division of Research Capacity Development under the Mid-Career Scientist Programme from funding received from the South African National Treasury. The content hereof is the sole responsibility of the authors and do not necessarily represent the official views of the SAMRC. L.J.Z also receives support from the National Research Foundation of South Africa (NRFSA), as well as the UK Medical Research Council (MRC) and the UK Department for International Development (DFID) under the MRC/DFID Concordat agreement, via the African Research Leader Award (MR/S005242/1). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The University of Cape Town Human Ethics Committee gave ethical approval for this work (HREC 599/2020, 401/2009, 190/2020 and 209/2020). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors

@article{Parsons2023,
abstract = {The epidemiology of human parainfluenza viruses (HPIV), particularly its role as a cause of acute respiratory infection (ARI) in infants, has not been formally studied in South Africa. We evaluated HPIV prevalence in diagnostic samples from hospitalized children from public sector hospitals in the Western Cape between 2014 and 2022. HPIV infection was detected in 2–10{\%} of patients, with the majority of infections detected in children less than 1 year of age. Prior to 2020, HPIV 4 (40{\%}) and HPIV 3 (34{\%}) were the most prevalent types, with seasonal peaks in late winter/spring for HPIV 3 and autumn/winter for HPIV 4. HPIV 4A and 4B co-circulated during the seasonal activity between 2014 and 2017. Pandemic restrictions in 2020 had a profound effect on HPIV circulation and the rebound was dominated by waves of HPIV 3, accounting for 66{\%} of detections and a sustained decline in the circulation of HPIV 1, 2 and 4. An immunity gap could account for the surge in HPIV 3 infections, but the decline in prior HPIV 4 dominance is unexplained and requires further study.},
author = {Parsons, Jane and Korsman, Stephen and Smuts, Heidi and Hsiao, Nei-Yuan and Valley-Omar, Ziyaad and Gelderbloem, Tathym and Hardie, Diana},
doi = {10.3390/diagnostics13152576},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Parsons et al. - 2023 - Human Parainfluenza Virus (HPIV) detection in hospitalized children with acute respiratory tract infection in th.pdf:pdf},
isbn = {2075-4418},
issn = {2075-4418},
journal = {Diagnostics},
keywords = {OA,OA{\_}PMC,South Africa,acute respiratory infection,children,epidemiology,fund{\_}ack,genomics{\_}fund{\_}ack,human parainfluenza virus,multiplex real-time PCR,original,pneumonia},
mendeley-tags = {OA,OA{\_}PMC,fund{\_}ack,genomics{\_}fund{\_}ack,original},
month = {aug},
number = {15},
pages = {2576},
pmid = {37568938},
title = {{Human Parainfluenza Virus (HPIV) detection in hospitalized children with acute respiratory tract infection in the Western Cape, South Africa during 2014–2022 reveals a shift in dominance of HPIV 3 and 4 infections}},
url = {https://www.mdpi.com/2075-4418/13/15/2576},
volume = {13},
year = {2023}
}

The epidemiology of human parainfluenza viruses (HPIV), particularly its role as a cause of acute respiratory infection (ARI) in infants, has not been formally studied in South Africa. We evaluated HPIV prevalence in diagnostic samples from hospitalized children from public sector hospitals in the Western Cape between 2014 and 2022. HPIV infection was detected in 2–10% of patients, with the majority of infections detected in children less than 1 year of age. Prior to 2020, HPIV 4 (40%) and HPIV 3 (34%) were the most prevalent types, with seasonal peaks in late winter/spring for HPIV 3 and autumn/winter for HPIV 4. HPIV 4A and 4B co-circulated during the seasonal activity between 2014 and 2017. Pandemic restrictions in 2020 had a profound effect on HPIV circulation and the rebound was dominated by waves of HPIV 3, accounting for 66% of detections and a sustained decline in the circulation of HPIV 1, 2 and 4. An immunity gap could account for the surge in HPIV 3 infections, but the decline in prior HPIV 4 dominance is unexplained and requires further study.

@article{Lesmes-Rodriguez2023,
abstract = {Background: Globally, the most significant risk factors for adverse COVID-19 outcome are increasing age and cardiometabolic comorbidities. However, underlying coinfections may modulate COVID-19 morbidity and mortality, particularly in regions with high prevalence of infectious diseases. Methods: We retrospectively analyzed serum samples for IgG antibodies against the common circulating coronaviruses HCoV-NL63, HCoV-229E, HCoV-OC43 and HCoV-HKU1 from non-hospitalized and hospitalized confirmed COVID-19 patients recruited during the first (June-August 2020) and second (October 2020-June 2021) COVID-19 wave in Cape Town, South Africa. Patients were grouped according to COVID-19 disease severity: Group 1: previously SARS-CoV-2 infected with positive serology and no symptoms (n=94); Group 2: acutely SARS-CoV-2 infected, hospitalized for COVID-19 and severe symptoms (n=92). Results: The overall anti-HCoV IgG seroprevalence in the entire patient cohort was 60.8{\%} (95{\%} CI: 53.7 – 67.8), with 37.1{\%} HCoV-NL63 (95{\%} CI: 30 – 44), 30.6{\%} HCoV-229E (95{\%} CI: 24 – 37.3), 22.6{\%} HCoV-HKU1 (95{\%} CI: 16.6 – 28.6), and 21.0{\%} HCoV-OC43 (95{\%} CI: 15.1 – 26.8). We observed a significantly higher overall HCoV presence (72.3{\%} versus 48.9{\%}) and coinfection frequency (43.6{\%} versus 19.6{\%}) in group 1 compared to group 2 patients with significantly higher presentation of HCoV-NL63 (67.0{\%} versus 6.6{\%}) and HCoV-HKU1 (31.1{\%} versus 14.1{\%}). However, only antibody titers for HCoV-NL63 were significantly higher in group 1 compared to group 2 patients (p {\textless} 0.0001, 1.90 [95{\%} CI: 0.62 – 2.45] versus 1.32 [95{\%} CI: 0.30 – 2.01]) which was independent of the participants' HIV status. Logistic regression analysis revealed significantly protective effects by previous exposure to HCoV-NL63 [p {\textless} 0.001, adjusted OR = 0.0176 (95{\%} CI: 0.0039 – 0.0786)], while previous HCoV-229E exposure was associated with increased COVID-19 severity [p = 0.0051, adjusted OR = 7.3239 (95{\%} CI: 1.8195–29.4800)]. Conclusion: We conclude that previous exposure to multiple common coronaviruses, and particularly HCoV-NL63, might protect against severe COVID-19, while no previous HCoV exposure or single infection with HCoV-229E might enhance the risk for severe COVID-19. To our knowledge, this is the first report on HCoV seroprevalence in South Africa and its possible association with cross-protection against COVID-19 severity.},
author = {Lesmes-Rodr{\'{i}}guez, Lida C and Lambarey, Humaira and Chetram, Abeen and Riou, Catherine and Wilkinson, Robert J and Joyimbana, Wendy and Jennings, Lauren and Orrell, Catherine and Jaramillo-Hern{\'{a}}ndez, Dumar A and Sch{\"{a}}fer, Georgia},
doi = {10.3389/FVIRO.2023.1125448/BIBTEX},
issn = {2673818X},
journal = {Frontiers in Virology},
keywords = {COVID-19,HCoV-229E,HCoV-HKU1,HCoV-NL63,HCoV-OC43,OA,SARS-CoV-2,Serology,fund{\_}ack,genomics{\_}fund{\_}ack,original},
mendeley-tags = {OA,fund{\_}ack,genomics{\_}fund{\_}ack,original},
month = {feb},
pages = {1125448},
publisher = {Frontiers Media SA},
title = {{Previous exposure to common coronavirus HCoV-NL63 is associated with reduced COVID-19 severity in patients from Cape Town, South Africa}},
volume = {3},
year = {2023}
}

Background: Globally, the most significant risk factors for adverse COVID-19 outcome are increasing age and cardiometabolic comorbidities. However, underlying coinfections may modulate COVID-19 morbidity and mortality, particularly in regions with high prevalence of infectious diseases. Methods: We retrospectively analyzed serum samples for IgG antibodies against the common circulating coronaviruses HCoV-NL63, HCoV-229E, HCoV-OC43 and HCoV-HKU1 from non-hospitalized and hospitalized confirmed COVID-19 patients recruited during the first (June-August 2020) and second (October 2020-June 2021) COVID-19 wave in Cape Town, South Africa. Patients were grouped according to COVID-19 disease severity: Group 1: previously SARS-CoV-2 infected with positive serology and no symptoms (n=94); Group 2: acutely SARS-CoV-2 infected, hospitalized for COVID-19 and severe symptoms (n=92). Results: The overall anti-HCoV IgG seroprevalence in the entire patient cohort was 60.8% (95% CI: 53.7 – 67.8), with 37.1% HCoV-NL63 (95% CI: 30 – 44), 30.6% HCoV-229E (95% CI: 24 – 37.3), 22.6% HCoV-HKU1 (95% CI: 16.6 – 28.6), and 21.0% HCoV-OC43 (95% CI: 15.1 – 26.8). We observed a significantly higher overall HCoV presence (72.3% versus 48.9%) and coinfection frequency (43.6% versus 19.6%) in group 1 compared to group 2 patients with significantly higher presentation of HCoV-NL63 (67.0% versus 6.6%) and HCoV-HKU1 (31.1% versus 14.1%). However, only antibody titers for HCoV-NL63 were significantly higher in group 1 compared to group 2 patients (p \textless 0.0001, 1.90 [95% CI: 0.62 – 2.45] versus 1.32 [95% CI: 0.30 – 2.01]) which was independent of the participants' HIV status. Logistic regression analysis revealed significantly protective effects by previous exposure to HCoV-NL63 [p \textless 0.001, adjusted OR = 0.0176 (95% CI: 0.0039 – 0.0786)], while previous HCoV-229E exposure was associated with increased COVID-19 severity [p = 0.0051, adjusted OR = 7.3239 (95% CI: 1.8195–29.4800)]. Conclusion: We conclude that previous exposure to multiple common coronaviruses, and particularly HCoV-NL63, might protect against severe COVID-19, while no previous HCoV exposure or single infection with HCoV-229E might enhance the risk for severe COVID-19. To our knowledge, this is the first report on HCoV seroprevalence in South Africa and its possible association with cross-protection against COVID-19 severity.

@article{Wertheim2022b,
abstract = {Recombination is an evolutionary process by which many pathogens generate diversity and acquire novel functions. Although a common occurrence during coronavirus replication, detection of recombination is only feasible when genetically distinct viruses contemporaneously infect the same host. Here, we identify an instance of SARS-CoV-2 superinfection, whereby an individual was infected with two distinct viral variants: Alpha (B.1.1.7) and Epsilon (B.1.429). This superinfection was first noted when an Alpha genome sequence failed to exhibit the classic S gene target failure behavior used to track this variant. Full genome sequencing from four independent extracts reveals that Alpha variant alleles comprise around 75{\%} of the genomes, whereas the Epsilon variant alleles comprise around 20{\%} of the sample. Further investigation reveals the presence of numerous recombinant haplotypes spanning the genome, specifically in the spike, nucleocapsid, and ORF 8 coding regions. These findings support the potential for recombination to reshape SARS-CoV-2 genetic diversity. Here, the authors characterize a case of SARS-CoV-2 superinfection with Alpha and Epsilon variants, in which, via full genome sequencing analyses, they identify recombinant haplotypes in the spike, nucleocapsid, and ORF 8 coding regions, suggesting recombination could play a role in SARS-CoV-2 genetic diversity.},
author = {Wertheim, Joel O and Wang, Jade C and Leelawong, Mindy and Martin, Darren P and Havens, Jennifer L and Chowdhury, Moinuddin A and Pekar, Jonathan E and Amin, Helly and Arroyo, Anthony and Awandare, Gordon A and Chow, Hoi Yan and Gonzalez, Edimarlyn and Luoma, Elizabeth and Morang'a, Collins M and Nekrutenko, Anton and Shank, Stephen D and Silver, Stefan and Quashie, Peter K and Rakeman, Jennifer L and Ruiz, Victoria and Torian, Lucia V and Vasylyeva, Tetyana I and {Kosakovsky Pond}, Sergei L and Hughes, Scott},
doi = {10.1038/s41467-022-31247-x},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Wertheim et al. - 2022 - Detection of SARS-CoV-2 intra-host recombination during superinfection with Alpha and Epsilon variants in New Y.pdf:pdf},
issn = {2041-1723},
journal = {Nature Communications},
keywords = {2,CoV,Molecular evolution,OA,Phylogenetics,SARS,genomics{\_}fund{\_}ack,original},
mendeley-tags = {OA,genomics{\_}fund{\_}ack,original},
month = {jun},
pages = {3645},
pmid = {35752633},
publisher = {Nature Publishing Group},
title = {{Detection of SARS-CoV-2 intra-host recombination during superinfection with Alpha and Epsilon variants in New York City}},
url = {https://www.nature.com/articles/s41467-022-31247-x},
volume = {13},
year = {2022}
}

Recombination is an evolutionary process by which many pathogens generate diversity and acquire novel functions. Although a common occurrence during coronavirus replication, detection of recombination is only feasible when genetically distinct viruses contemporaneously infect the same host. Here, we identify an instance of SARS-CoV-2 superinfection, whereby an individual was infected with two distinct viral variants: Alpha (B.1.1.7) and Epsilon (B.1.429). This superinfection was first noted when an Alpha genome sequence failed to exhibit the classic S gene target failure behavior used to track this variant. Full genome sequencing from four independent extracts reveals that Alpha variant alleles comprise around 75% of the genomes, whereas the Epsilon variant alleles comprise around 20% of the sample. Further investigation reveals the presence of numerous recombinant haplotypes spanning the genome, specifically in the spike, nucleocapsid, and ORF 8 coding regions. These findings support the potential for recombination to reshape SARS-CoV-2 genetic diversity. Here, the authors characterize a case of SARS-CoV-2 superinfection with Alpha and Epsilon variants, in which, via full genome sequencing analyses, they identify recombinant haplotypes in the spike, nucleocapsid, and ORF 8 coding regions, suggesting recombination could play a role in SARS-CoV-2 genetic diversity.

@article{Blumenthal2022,
abstract = {In South Africa, the COVID-19 pandemic occurs against the backdrop of high Human Immunodeficiency Virus (HIV-1), tuberculosis (TB) and non-communicable disease burdens as well as prevalent herpesviruses infections such as Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV). As part of an observational study of adults admitted to Groote Schuur Hospital, Cape Town, South Africa, during the period June – August 2020 and assessed for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, we measured KSHV serology and KSHV and EBV viral load (VL) in peripheral blood in relation to Coronavirus disease 2019 (COVID-19) severity and outcome. A total of 104 patients with PCR-confirmed SARS-CoV-2 infection were included. 61{\%} were men and 39{\%} women with a median age of 53 years (range 21 – 86). 29.8{\%} (95{\%} CI: 21.7 – 39.1{\%}) of the cohort was HIV-1 positive and 41.1{\%} (95{\%} CI: 31.6 – 51.1{\%}) were KSHV seropositive. EBV VL was detectable in 84.4{\%} (95{\%} CI: 76.1 – 84.4{\%}) of the cohort while KSHV DNA was detected in 20.6{\%} (95{\%} CI: 13.6 – 29.2{\%}), with dual EBV/KSHV infection in 17.7{\%} (95{\%} CI: 11.1 – 26.2{\%}). On enrolment, 48 (46.2{\%} (95{\%} CI: 36.8 – 55.7{\%})) COVID-19 patients were classified as severe on the WHO ordinal scale reflecting oxygen therapy and supportive care requirements; 30 of these patients (28.8{\%} (95{\%} CI: 20.8 – 38.0{\%}) died. In COVID-19 patients, detectable KSHV VL was associated with death after adjusting for age, sex, HIV-1 status and detectable EBV VL (p=0.036, adjusted OR=3.17 [95{\%} CI: 1.08 – 9.32]). Furthermore, in HIV-1 negative COVID-19 patients, there was a trend indicating that KSHV VL was related to COVID-19 disease severity (p=0.054, unstandardized co-efficient 0.86 [95{\%} CI: -0.015 – 1.74]) in addition to death (p=0.008, adjusted OR=7.34 [95{\%} CI: 1.69 – 31.49]). While the design of our study cannot distinguish if disease synergy exists between COVID-19 and KSHV nor if either viral infection is fueling the other, these data point to a potential contribution of KSHV infection to COVID-19 outcome, or SARS-CoV-2 infection to KSHV reactivation, particularly in the South African context of high disease burden, that warrants further investigation.},
author = {Blumenthal, Melissa J and Lambarey, Humaira and Chetram, Abeen and Riou, Catherine and Wilkinson, Robert J and Sch{\"{a}}fer, Georgia},
doi = {10.3389/FMICB.2021.795555},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Blumenthal et al. - 2022 - Kaposi's sarcoma-associated herpesvirus, but not Epstein-Barr virus, co-infection associates with coronavirus.pdf:pdf},
issn = {1664-302X},
journal = {Frontiers in Microbiology},
keywords = {COVID-19,KSHV,OA,OA{\_}PMC,SARS-CoV-2,South Africa,fund{\_}ack,genomics{\_}fund{\_}ack,lytic reactivation,original},
mendeley-tags = {OA,OA{\_}PMC,fund{\_}ack,genomics{\_}fund{\_}ack,original},
month = {jan},
pages = {795555},
pmid = {35069495},
publisher = {Frontiers},
title = {{Kaposi's sarcoma-associated herpesvirus, but not Epstein-Barr virus, co-infection associates with coronavirus disease 2019 severity and outcome in South African patients}},
url = {https://www.frontiersin.org/articles/10.3389/fmicb.2021.795555/full},
volume = {12},
year = {2022}
}

In South Africa, the COVID-19 pandemic occurs against the backdrop of high Human Immunodeficiency Virus (HIV-1), tuberculosis (TB) and non-communicable disease burdens as well as prevalent herpesviruses infections such as Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV). As part of an observational study of adults admitted to Groote Schuur Hospital, Cape Town, South Africa, during the period June – August 2020 and assessed for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, we measured KSHV serology and KSHV and EBV viral load (VL) in peripheral blood in relation to Coronavirus disease 2019 (COVID-19) severity and outcome. A total of 104 patients with PCR-confirmed SARS-CoV-2 infection were included. 61% were men and 39% women with a median age of 53 years (range 21 – 86). 29.8% (95% CI: 21.7 – 39.1%) of the cohort was HIV-1 positive and 41.1% (95% CI: 31.6 – 51.1%) were KSHV seropositive. EBV VL was detectable in 84.4% (95% CI: 76.1 – 84.4%) of the cohort while KSHV DNA was detected in 20.6% (95% CI: 13.6 – 29.2%), with dual EBV/KSHV infection in 17.7% (95% CI: 11.1 – 26.2%). On enrolment, 48 (46.2% (95% CI: 36.8 – 55.7%)) COVID-19 patients were classified as severe on the WHO ordinal scale reflecting oxygen therapy and supportive care requirements; 30 of these patients (28.8% (95% CI: 20.8 – 38.0%) died. In COVID-19 patients, detectable KSHV VL was associated with death after adjusting for age, sex, HIV-1 status and detectable EBV VL (p=0.036, adjusted OR=3.17 [95% CI: 1.08 – 9.32]). Furthermore, in HIV-1 negative COVID-19 patients, there was a trend indicating that KSHV VL was related to COVID-19 disease severity (p=0.054, unstandardized co-efficient 0.86 [95% CI: -0.015 – 1.74]) in addition to death (p=0.008, adjusted OR=7.34 [95% CI: 1.69 – 31.49]). While the design of our study cannot distinguish if disease synergy exists between COVID-19 and KSHV nor if either viral infection is fueling the other, these data point to a potential contribution of KSHV infection to COVID-19 outcome, or SARS-CoV-2 infection to KSHV reactivation, particularly in the South African context of high disease burden, that warrants further investigation.

@article{Lucaciid2022,
abstract = {An important unmet need revealed by the COVID-19 pandemic is the near-real-time identification of potentially fitness-altering mutations within rapidly growing SARS-CoV-2 lineages. Although powerful molecular sequence analysis methods are available to detect and characterize patterns of natural selection within modestly sized gene-sequence datasets, the computational complexity of these methods and their sensitivity to sequencing errors render them effectively inapplicable in large-scale genomic surveillance contexts. Motivated by the need to analyze new lineage evolution in near-real time using large numbers of genomes, we developed the Rapid Assessment of Selection within CLades (RASCL) pipeline. RASCL applies state of the art phylogenetic comparative methods to evaluate selective processes acting at individual codon sites and across whole genes. RASCL is scalable and produces automatically updated regular lineage-specific selection analysis reports: even for lineages that include tens or hundreds of thousands of sampled genome sequences. Key to this performance is (i) generation of automatically subsampled high quality datasets of gene/ORF sequences drawn from a selected “query” viral lineage; (ii) contextualization of these query sequences in codon alignments that include high-quality “background” sequences representative of global SARS-CoV-2 diversity; and (iii) the extensive parallelization of a suite of computationally intensive selection analysis tests. Within hours of being deployed to analyze a novel rapidly growing lineage of interest, RASCL will begin yielding JavaScript Object Notation (JSON)-formatted reports that can be either imported into third-party analysis software or explored in standard web-browsers using the premade RASCL interactive data visualization dashboard. By enabling the rapid detection of genome sites evolving under different selective regimes, RASCL is well-suited for near-real-time monitoring of the population-level selective processes that will likely underlie the emergence of future variants of concern in measurably evolving pathogens with extensive genomic surveillance.},
author = {Lucaciid, Alexander G and Zehr, Jordan D and Shank, Stephen D and Bouvier, Dave and Ostrovskyid, Alexander and Meiid, Han and Nekrutenko, Anton and Martin, Darren P and {Kosakovsky Pondid}, Sergei L},
doi = {10.1371/JOURNAL.PONE.0275623},
editor = {Makarenkov, Vladimir},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Lucaciid et al. - 2022 - RASCL Rapid Assessment of Selection in CLades through molecular sequence analysis.pdf:pdf},
isbn = {1111111111},
issn = {1932-6203},
journal = {PLOS ONE},
keywords = {Evolutionary genetics,Gene prediction,Genome analysis,Genomics,OA,Phylogenetic analysis,SARS CoV 2,Viral evolution,Virus testing,genomics{\_}fund{\_}ack,original},
mendeley-tags = {OA,genomics{\_}fund{\_}ack,original},
month = {nov},
number = {11},
pages = {e0275623},
pmid = {36322581},
publisher = {Public Library of Science},
title = {{RASCL: Rapid Assessment of Selection in CLades through molecular sequence analysis}},
url = {https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0275623},
volume = {17},
year = {2022}
}

An important unmet need revealed by the COVID-19 pandemic is the near-real-time identification of potentially fitness-altering mutations within rapidly growing SARS-CoV-2 lineages. Although powerful molecular sequence analysis methods are available to detect and characterize patterns of natural selection within modestly sized gene-sequence datasets, the computational complexity of these methods and their sensitivity to sequencing errors render them effectively inapplicable in large-scale genomic surveillance contexts. Motivated by the need to analyze new lineage evolution in near-real time using large numbers of genomes, we developed the Rapid Assessment of Selection within CLades (RASCL) pipeline. RASCL applies state of the art phylogenetic comparative methods to evaluate selective processes acting at individual codon sites and across whole genes. RASCL is scalable and produces automatically updated regular lineage-specific selection analysis reports: even for lineages that include tens or hundreds of thousands of sampled genome sequences. Key to this performance is (i) generation of automatically subsampled high quality datasets of gene/ORF sequences drawn from a selected “query” viral lineage; (ii) contextualization of these query sequences in codon alignments that include high-quality “background” sequences representative of global SARS-CoV-2 diversity; and (iii) the extensive parallelization of a suite of computationally intensive selection analysis tests. Within hours of being deployed to analyze a novel rapidly growing lineage of interest, RASCL will begin yielding JavaScript Object Notation (JSON)-formatted reports that can be either imported into third-party analysis software or explored in standard web-browsers using the premade RASCL interactive data visualization dashboard. By enabling the rapid detection of genome sites evolving under different selective regimes, RASCL is well-suited for near-real-time monitoring of the population-level selective processes that will likely underlie the emergence of future variants of concern in measurably evolving pathogens with extensive genomic surveillance.

@article{Hussey2022a,
abstract = {Abstract Background The extent to which the reduced risk of severe disease seen with SARS-CoV-2 Omicron is due to a decrease in variant virulence, or higher levels of population immunity, is currently not clear. Methods RdRp target delay (RTD) in the Seegene AllplexTM 2019-nCoV PCR assay is a proxy marker for the Delta variant. The absence of this proxy marker in the transition period was used to identify suspected Omicron infections. Cox regression was performed for the outcome of hospital admission in those who tested positive for SARS-CoV-2 on the Seegene AllplexTM assay from 1 November to 14 December 2021 in the Western Cape Province, South Africa, public sector. Vaccination status and prior diagnosed infection, were adjusted for. Results 150 cases with RTD and 1486 cases without RTD were included. Cases without RTD had a lower hazard of admission (adjusted Hazard Ratio [aHR] of 0.56, 95{\%}CI 0.34-0.91). Complete vaccination was protective of admission with an aHR of 0.45 (95{\%}CI 0.26-0.77). Conclusion Omicron has resulted in a lower risk of hospital admission, compared to contemporaneous Delta infection, when using the proxy marker of RTD. Under-ascertainment of reinfections with an immune escape variant remains a challenge to accurately assessing variant virulence.},
author = {Hussey, Hannah and Davies, Mary-Ann and Heekes, Alexa and Williamson, Carolyn and Valley-Omar, Ziyaad and Hardie, Diana and Korsman, Stephen and Doolabh, Deelan and Preiser, Wolfgang and Maponga, Tongai and Iranzadeh, Arash and Wasserman, Sean and Boloko, Linda and Symons, Greg and Raubenheimer, Peter and Parker, Arifa and Schrueder, Neshaad and Solomon, Wesley and Rousseau, Petro and Wolter, Nicole and Jassat, Waasila and Cohen, Cheryl and Lessells, Richard and Wilkinson, Robert J and Boulle, Andrew and Hsiao, Nei-yuan},
doi = {10.1016/J.IJID.2022.02.051},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Hussey et al. - 2022 - Assessing the clinical severity of the Omicron variant in the Western Cape Province, South Africa, using the d(2).pdf:pdf},
issn = {1201-9712},
journal = {International Journal of Infectious Diseases},
keywords = {OA,Omicron variant,RdRp target delay,SARS-CoV-2,South Africa,clinical severity,fund{\_}ack,genomics{\_}fund{\_}ack,original},
mendeley-tags = {OA,fund{\_}ack,genomics{\_}fund{\_}ack,original},
month = {feb},
pages = {150--154},
pmid = {35235826},
publisher = {Elsevier},
title = {{Assessing the clinical severity of the Omicron variant in the Western Cape Province, South Africa, using the diagnostic PCR proxy marker of RdRp target delay to distinguish between Omicron and Delta infections – a survival analysis}},
url = {http://www.ijidonline.com/article/S1201971222001291/fulltext http://www.ijidonline.com/article/S1201971222001291/abstract https://www.ijidonline.com/article/S1201-9712(22)00129-1/abstract},
volume = {118},
year = {2022}
}

Abstract Background The extent to which the reduced risk of severe disease seen with SARS-CoV-2 Omicron is due to a decrease in variant virulence, or higher levels of population immunity, is currently not clear. Methods RdRp target delay (RTD) in the Seegene AllplexTM 2019-nCoV PCR assay is a proxy marker for the Delta variant. The absence of this proxy marker in the transition period was used to identify suspected Omicron infections. Cox regression was performed for the outcome of hospital admission in those who tested positive for SARS-CoV-2 on the Seegene AllplexTM assay from 1 November to 14 December 2021 in the Western Cape Province, South Africa, public sector. Vaccination status and prior diagnosed infection, were adjusted for. Results 150 cases with RTD and 1486 cases without RTD were included. Cases without RTD had a lower hazard of admission (adjusted Hazard Ratio [aHR] of 0.56, 95%CI 0.34-0.91). Complete vaccination was protective of admission with an aHR of 0.45 (95%CI 0.26-0.77). Conclusion Omicron has resulted in a lower risk of hospital admission, compared to contemporaneous Delta infection, when using the proxy marker of RTD. Under-ascertainment of reinfections with an immune escape variant remains a challenge to accurately assessing variant virulence.

@article{Wertheim2022a,
abstract = {Recombination is an evolutionary process by which many pathogens generate diversity and acquire novel functions. Although a common occurrence during coronavirus replication, recombination can only be detected when two genetically distinct viruses contemporaneously infect the same host. Here, we identify an instance of SARS-CoV-2 superinfection, whereby an individual was simultaneously infected with two distinct viral variants: Alpha (B.1.1.7) and Epsilon (B.1.429). This superinfection was first noted when an Alpha genome sequence failed to exhibit the classic S gene target failure behavior used to track this variant. Full genome sequencing from four independent extracts revealed that Alpha variant alleles comprised between 70-80{\%} of the genomes, whereas the Epsilon variant alleles comprised between 20-30{\%} of the sample. Further investigation revealed the presence of numerous recombinant haplotypes spanning the genome, specifically in the spike, nucleocapsid, and ORF 8 coding regions. These findings support the potential for recombination to reshape SARS-CoV-2 genetic diversity. {\#}{\#}{\#} Competing Interest Statement J.O.W. and S.L.K.P has received funding from the CDC (ongoing) via contracts or agreements to their institution unrelated to this research. All other authors declare no competing interests. {\#}{\#}{\#} Funding Statement J.O.W. acknowledges funding from the National Institutes of Health (AI135992 and AI136056). D.P.M was funded by the Wellcome Trust (222574/Z/21/Z). PKQ is funded by a Crick African Network Fellowship. T.I.V. is funded by a Branco Weiss Fellowship. S.L.K.P and A.N were supported in part by a grant from the National Institutes of Health (AI134384). This work was supported (in part) by the Epidemiology and Laboratory Capacity (ELC) for Infectious Diseases Cooperative Agreement (Grant Number: ELC DETECT (6NU50CK000517-01-07) funded by the Centers for Disease Control and Prevention (CDC). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of CDC or the Department of Health and Human Services. {\#}{\#}{\#} Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: IRB of UC San Diego waived gave ethical approval of this work as human subjects except. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes The data analyzed as part of this project were obtained from the GISAID database and through a Data Use Agreement between NYC DOHMH and the University of California San Diego. We gratefully acknowledge the authors from the originating laboratories and the submitting laboratories, who generated and shared via GISAID the viral genomic sequence data on which this research is based. A complete list acknowledging the authors who submitted the data analyzed in this study can be found in Data S1. Trimmed, host-depleted viral sequencing data and cloned sequence fragments have been submitted to NCBI (accession numbers pending).},
author = {Wertheim, Joel O and Wang, Jade C and Leelawong, Mindy and Martin, Darren P and Havens, Jennifer L and Chowdhury, Moinuddin A and Pekar, Jonathan and Amin, Helly and Arroyo, Anthony and Awandare, Gordon A and Chow, Hoi Yan and Gonzalez, Edimarlyn and Luoma, Elizabeth and Morang'a, Collins M and Nekrutenko, Anton and Shank, Stephen D and Quashie, Peter K and Rakeman, Jennifer L and Ruiz, Victoria and Torian, Lucia V and Vasylyeva, Tetyana I and Pond, Sergei L. Kosakovsky and Hughes, Scott},
doi = {10.1101/2022.01.18.22269300},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Wertheim et al. - 2022 - Capturing intrahost recombination of SARS-CoV-2 during superinfection with Alpha and Epsilon variants in New(2).pdf:pdf},
journal = {medRxiv},
keywords = {OA,genomics{\_}fund{\_}ack,original},
mendeley-tags = {OA,genomics{\_}fund{\_}ack,original},
month = {jan},
pages = {2022.01.18.22269300},
publisher = {Cold Spring Harbor Laboratory Press},
title = {{Capturing intrahost recombination of SARS-CoV-2 during superinfection with Alpha and Epsilon variants in New York City}},
url = {https://www.medrxiv.org/content/10.1101/2022.01.18.22269300v1 https://www.medrxiv.org/content/10.1101/2022.01.18.22269300v1.abstract},
year = {2022}
}

Recombination is an evolutionary process by which many pathogens generate diversity and acquire novel functions. Although a common occurrence during coronavirus replication, recombination can only be detected when two genetically distinct viruses contemporaneously infect the same host. Here, we identify an instance of SARS-CoV-2 superinfection, whereby an individual was simultaneously infected with two distinct viral variants: Alpha (B.1.1.7) and Epsilon (B.1.429). This superinfection was first noted when an Alpha genome sequence failed to exhibit the classic S gene target failure behavior used to track this variant. Full genome sequencing from four independent extracts revealed that Alpha variant alleles comprised between 70-80% of the genomes, whereas the Epsilon variant alleles comprised between 20-30% of the sample. Further investigation revealed the presence of numerous recombinant haplotypes spanning the genome, specifically in the spike, nucleocapsid, and ORF 8 coding regions. These findings support the potential for recombination to reshape SARS-CoV-2 genetic diversity. ### Competing Interest Statement J.O.W. and S.L.K.P has received funding from the CDC (ongoing) via contracts or agreements to their institution unrelated to this research. All other authors declare no competing interests. ### Funding Statement J.O.W. acknowledges funding from the National Institutes of Health (AI135992 and AI136056). D.P.M was funded by the Wellcome Trust (222574/Z/21/Z). PKQ is funded by a Crick African Network Fellowship. T.I.V. is funded by a Branco Weiss Fellowship. S.L.K.P and A.N were supported in part by a grant from the National Institutes of Health (AI134384). This work was supported (in part) by the Epidemiology and Laboratory Capacity (ELC) for Infectious Diseases Cooperative Agreement (Grant Number: ELC DETECT (6NU50CK000517-01-07) funded by the Centers for Disease Control and Prevention (CDC). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of CDC or the Department of Health and Human Services. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: IRB of UC San Diego waived gave ethical approval of this work as human subjects except. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes The data analyzed as part of this project were obtained from the GISAID database and through a Data Use Agreement between NYC DOHMH and the University of California San Diego. We gratefully acknowledge the authors from the originating laboratories and the submitting laboratories, who generated and shared via GISAID the viral genomic sequence data on which this research is based. A complete list acknowledging the authors who submitted the data analyzed in this study can be found in Data S1. Trimmed, host-depleted viral sequencing data and cloned sequence fragments have been submitted to NCBI (accession numbers pending).

@article{Martin2022,
abstract = {Among the 30 non-synonymous nucleotide substitutions in the Omicron S-gene are 13 that have only rarely been seen in other SARS-CoV-2 sequences. These mutations cluster within three functionally important regions of the S-gene at sites that will likely impact (i) interactions between subunits of the Spike trimer and the predisposition of subunits to shift from down to up configurations, (ii) interactions of Spike with ACE2 receptors, and (iii) the priming of Spike for membrane fusion. We show here that, based on both the rarity of these 13 mutations in intrapatient sequencing reads and patterns of selection at the codon sites where the mutations occur in SARS-CoV-2 and related sarbecoviruses, prior to the emergence of Omicron the mutations would have been predicted to decrease the fitness of any genomes within which they occurred. We further propose that the mutations in each of the three clusters therefore cooperatively interact to both mitigate their individual fitness costs, and adaptively alter the function of Spike. Given the evident epidemic growth advantages of Omicron over all previously known SARS-CoV-2 lineages, it is crucial to determine both how such complex and highly adaptive mutation constellations were assembled within the Omicron S-gene, and why, despite unprecedented global genomic surveillance efforts, the early stages of this assembly process went completely undetected. {\#}{\#}{\#} Competing Interest Statement JDB consults for Moderna, Flagship Labs 77, and Oncorus. JDB, AJG, and TNS are inventors on Fred Hutch licensed patents related to deep mutational scanning of viral proteins.},
author = {Martin, Darren P and Lytras, Spyros and Lucaci, Alexander G and Maier, Wolfgang and Gr{\"{u}}ning, Bj{\"{o}}rn and Shank, Stephen D and Weaver, Steven and MacLean, Oscar A and Orton, Richard J and Lemey, Philippe and Boni, Maciej F and Tegally, Houriiyah and Harkins, Gordon and Scheepers, Cathrine and Bhiman, Jinal N and Everatt, Josie and Amoako, Daniel G and San, James Emmanuel and Giandhari, Jennifer and Sigal, Alex and NGS-SA and Williamson, Carolyn and Hsiao, Nei-yuan and von Gottberg, Anne and Klerk, Arne De and Shafer, Robert W and Robertson, David L and Wilkinson, Robert J and Sewell, B Trevor and Lessells, Richard and Nekrutenko, Anton and Greaney, Allison J. and Starr, Tyler N. and Bloom, Jesse D. and Murrell, Ben and Wilkinson, Eduan and Gupta, Ravindra K and de Oliveira, Tulio and Pond, Sergei L Kosakovsky},
doi = {10.1101/2022.01.14.476382},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Martin et al. - 2022 - Selection analysis identifies unusual clustered mutational changes in Omicron lineage BA.1 that likely impact Spi.pdf:pdf},
journal = {bioRxiv},
keywords = {OA,OA{\_}PMC,fund{\_}ack,genomics{\_}fund{\_}ack,original},
mendeley-tags = {OA,OA{\_}PMC,fund{\_}ack,genomics{\_}fund{\_}ack,original},
month = {jan},
pages = {2022.01.14.476382},
pmid = {35075456},
publisher = {Cold Spring Harbor Laboratory},
title = {{Selection analysis identifies unusual clustered mutational changes in Omicron lineage BA.1 that likely impact Spike function}},
url = {https://www.biorxiv.org/content/10.1101/2022.01.14.476382v1 https://www.biorxiv.org/content/10.1101/2022.01.14.476382v1.abstract},
year = {2022}
}

Among the 30 non-synonymous nucleotide substitutions in the Omicron S-gene are 13 that have only rarely been seen in other SARS-CoV-2 sequences. These mutations cluster within three functionally important regions of the S-gene at sites that will likely impact (i) interactions between subunits of the Spike trimer and the predisposition of subunits to shift from down to up configurations, (ii) interactions of Spike with ACE2 receptors, and (iii) the priming of Spike for membrane fusion. We show here that, based on both the rarity of these 13 mutations in intrapatient sequencing reads and patterns of selection at the codon sites where the mutations occur in SARS-CoV-2 and related sarbecoviruses, prior to the emergence of Omicron the mutations would have been predicted to decrease the fitness of any genomes within which they occurred. We further propose that the mutations in each of the three clusters therefore cooperatively interact to both mitigate their individual fitness costs, and adaptively alter the function of Spike. Given the evident epidemic growth advantages of Omicron over all previously known SARS-CoV-2 lineages, it is crucial to determine both how such complex and highly adaptive mutation constellations were assembled within the Omicron S-gene, and why, despite unprecedented global genomic surveillance efforts, the early stages of this assembly process went completely undetected. ### Competing Interest Statement JDB consults for Moderna, Flagship Labs 77, and Oncorus. JDB, AJG, and TNS are inventors on Fred Hutch licensed patents related to deep mutational scanning of viral proteins.

@article{Scheepers2022,
abstract = {Global genomic surveillance of SARS-CoV-2 has identified variants associated with increased transmissibility, neutralization resistance and disease severity. Here we report the emergence of the PANGO lineage C.1.2, detected at low prevalence in South Africa and eleven other countries. The initial C.1.2 detection is associated with a high substitution rate, and includes changes within the spike protein that have been associated with increased transmissibility or reduced neutralization sensitivity in SARS-CoV-2 variants of concern or variants of interest. Like Beta and Delta, C.1.2 shows significantly reduced neutralization sensitivity to plasma from vaccinees and individuals infected with the ancestral D614G virus. In contrast, convalescent donors infected with either Beta or Delta show high plasma neutralization against C.1.2. These functional data suggest that vaccine efficacy against C.1.2 will be equivalent to Beta and Delta, and that prior infection with either Beta or Delta will likely offer protection against C.1.2. The SARS-CoV-2 PANGO lineage C.1.2 has been under monitoring by global health authorities as it has spread worldwide. Here, Bhiman and colleagues characterise the emergence of the lineage, and its neutralisation sensitivity using data from vaccinees and previously infected individuals.},
author = {Scheepers, Cathrine and Everatt, Josie and Amoako, Daniel G and Tegally, Houriiyah and Wibmer, Constantinos Kurt and Mnguni, Anele and Ismail, Arshad and Mahlangu, Boitshoko and Lambson, Bronwen E and Martin, Darren P and Wilkinson, Eduan and San, James Emmanuel and Giandhari, Jennifer and Manamela, Nelia and Ntuli, Noxolo and Kgagudi, Prudence and Cele, Sandile and Richardson, Simone I and Pillay, Sureshnee and Mohale, Thabo and Ramphal, Upasana and Naidoo, Yeshnee and Khumalo, Zamantungwa T and Kwatra, Gaurav and Gray, Glenda and Bekker, Linda-Gail and Madhi, Shabir A and Baillie, Vicky and {Van Voorhis}, Wesley C and Treurnicht, Florette K and Venter, Marietjie and Mlisana, Koleka and Wolter, Nicole and Sigal, Alex and Williamson, Carolyn and Hsiao, Nei-yuan and Msomi, Nokukhanya and Maponga, Tongai and Preiser, Wolfgang and Makatini, Zinhle and Lessells, Richard and Moore, Penny L and de Oliveira, Tulio and von Gottberg, Anne and Bhiman, Jinal N},
doi = {10.1038/s41467-022-29579-9},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Scheepers et al. - 2022 - Emergence and phenotypic characterization of the global SARS-CoV-2 C.1.2 lineage.pdf:pdf},
issn = {2041-1723},
journal = {Nature Communications},
keywords = {2,CoV,Epidemiology,OA,SARS,Viral infection,genomics{\_}fund{\_}ack,original},
mendeley-tags = {OA,genomics{\_}fund{\_}ack,original},
month = {apr},
pages = {1976},
pmid = {35396511},
publisher = {Nature Publishing Group},
title = {{Emergence and phenotypic characterization of the global SARS-CoV-2 C.1.2 lineage}},
url = {https://www.nature.com/articles/s41467-022-29579-9},
volume = {13},
year = {2022}
}

Global genomic surveillance of SARS-CoV-2 has identified variants associated with increased transmissibility, neutralization resistance and disease severity. Here we report the emergence of the PANGO lineage C.1.2, detected at low prevalence in South Africa and eleven other countries. The initial C.1.2 detection is associated with a high substitution rate, and includes changes within the spike protein that have been associated with increased transmissibility or reduced neutralization sensitivity in SARS-CoV-2 variants of concern or variants of interest. Like Beta and Delta, C.1.2 shows significantly reduced neutralization sensitivity to plasma from vaccinees and individuals infected with the ancestral D614G virus. In contrast, convalescent donors infected with either Beta or Delta show high plasma neutralization against C.1.2. These functional data suggest that vaccine efficacy against C.1.2 will be equivalent to Beta and Delta, and that prior infection with either Beta or Delta will likely offer protection against C.1.2. The SARS-CoV-2 PANGO lineage C.1.2 has been under monitoring by global health authorities as it has spread worldwide. Here, Bhiman and colleagues characterise the emergence of the lineage, and its neutralisation sensitivity using data from vaccinees and previously infected individuals.

@article{Hussey2022b,
abstract = {Background: The SARS-CoV-2 Delta variant (B.1.617.2) has been associated with more severe disease, particularly when compared to the Alpha variant. Most of this data, however, is from high income countries and less is understood about the variant's disease severity in other settings, particularly in an African context, and when compared to the Beta variant. Methods: A novel proxy marker, RNA-dependent RNA polymerase (RdRp) target delay in the Seegene Allplex TM 2019-nCoV (polymerase chain reaction) PCR assay, was used to identify suspected Delta variant infection in routine laboratory data. All cases diagnosed on this assay in the public sector in the Western Cape, South Africa, from 1 April to 31 July 2021, were included in the dataset provided by the Western Cape Provincial Health Data Centre (PHDC). The PHDC collates information on all COVID-19 related laboratory tests, hospital admissions and deaths for the province. Odds ratios for the association between the proxy marker and death were calculated, adjusted for prior diagnosed infection and vaccination status. Results: A total of 11,355 cases with 700 deaths were included in this study. RdRp target delay (suspected Delta variant) was associated with higher mortality (adjusted odds ratio [aOR] 1.45; 95{\%} confidence interval [CI]: 1.13-1.86), compared to presumptive Beta infection. Prior diagnosed infection during the previous COVID-19 wave, which was driven by the Beta variant, was protective (aOR 0.32; 95{\%}CI: 0.11-0.92) as was vaccination (aOR [95{\%}CI] 0.15 [0.03-0.62] for complete vaccination [≥28 days post a single dose of Ad26.COV2.S or ≥14 days post second BNT162b2 dose]). Conclusion: RdRp target delay, a proxy for infection with the Delta variant, is associated with an increased risk of mortality amongst those who were tested for COVID-19 in our setting.},
author = {Hussey, Hannah and Davies, Mary-Ann and Heekes, Alexa and Williamson, Carolyn and Valley-Omar, Ziyaad and Hardie, Diana and Korsman, Stephen and Doolabh, Deelan and Preiser, Wofgang and Maponga, Tongai and Iranzadeh, Arash and Engelbrecht, Susan and Wasserman, Sean and Schrueder, Neshaad and Boloko, Linda and Symons, Greg and Raubenheimer, Peter and Viljoen, Abraham and Parker, Arifa and Cohen, Cheryl and Jasat, Waasila and Lessells, Richard and Wilkinson, Robert J and Boulle, Andrew and Hsiao, Marvin},
doi = {10.12688/gatesopenres.13654.1},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Hussey et al. - 2022 - Higher mortality associated with the SARS-CoV-2 Delta variant in the Western Cape, South Africa, using RdRp targe.pdf:pdf},
journal = {Gates Open Research},
keywords = {B.1.617.2,Delta,OA,RdRp target delay,SARS-CoV-2,South Africa,clinical severity,fund{\_}ack,genomics{\_}fund{\_}ack,original},
mendeley-tags = {OA,fund{\_}ack,genomics{\_}fund{\_}ack,original},
month = {aug},
pages = {117},
pmid = {37994361},
publisher = {F1000 Research Limited},
title = {{Higher mortality associated with the SARS-CoV-2 Delta variant in the Western Cape, South Africa, using RdRp target delay as a proxy: a cross-sectional study. [version 1; peer review: 2 approved]}},
url = {https://gatesopenresearch.org/articles/6-117},
volume = {6},
year = {2022}
}

Background: The SARS-CoV-2 Delta variant (B.1.617.2) has been associated with more severe disease, particularly when compared to the Alpha variant. Most of this data, however, is from high income countries and less is understood about the variant's disease severity in other settings, particularly in an African context, and when compared to the Beta variant. Methods: A novel proxy marker, RNA-dependent RNA polymerase (RdRp) target delay in the Seegene Allplex TM 2019-nCoV (polymerase chain reaction) PCR assay, was used to identify suspected Delta variant infection in routine laboratory data. All cases diagnosed on this assay in the public sector in the Western Cape, South Africa, from 1 April to 31 July 2021, were included in the dataset provided by the Western Cape Provincial Health Data Centre (PHDC). The PHDC collates information on all COVID-19 related laboratory tests, hospital admissions and deaths for the province. Odds ratios for the association between the proxy marker and death were calculated, adjusted for prior diagnosed infection and vaccination status. Results: A total of 11,355 cases with 700 deaths were included in this study. RdRp target delay (suspected Delta variant) was associated with higher mortality (adjusted odds ratio [aOR] 1.45; 95% confidence interval [CI]: 1.13-1.86), compared to presumptive Beta infection. Prior diagnosed infection during the previous COVID-19 wave, which was driven by the Beta variant, was protective (aOR 0.32; 95%CI: 0.11-0.92) as was vaccination (aOR [95%CI] 0.15 [0.03-0.62] for complete vaccination [≥28 days post a single dose of Ad26.COV2.S or ≥14 days post second BNT162b2 dose]). Conclusion: RdRp target delay, a proxy for infection with the Delta variant, is associated with an increased risk of mortality amongst those who were tested for COVID-19 in our setting.

@article{DeKlerk2022,
abstract = {Recombination contributes to the genetic diversity found in coronaviruses and is known to be a prominent mechanism whereby they evolve. It is apparent, both from controlled experiments and in genome sequences sampled from nature, that patterns of recombination in coronaviruses are non-random and that this is likely attributable to a combination of sequence features that favour the occurrence of recombination break points at specific genomic sites, and selection disfavouring the survival of recombinants within which favourable intra-genome interactions have been disrupted. Here we leverage available whole-genome sequence data for six coronavirus subgenera to identify specific patterns of recombination that are conserved between multiple subgenera and then identify the likely factors that underlie these conserved patterns. Specifically, we confirm the non-randomness of recombination break points across all six tested coronavirus subgenera, locate conserved recombination hot- and cold-spots, and determine that the locations of transcriptional regulatory sequences are likely major determinants of conserved recombination break-point hotspot locations. We find that while the locations of recombination break points are not uniformly associated with degrees of nucleotide sequence conservation, they display significant tendencies in multiple coronavirus subgenera to occur in low guanine-cytosine content genome regions, in non-coding regions, at the edges of genes, and at sites within the Spike gene that are predicted to be minimally disruptive of Spike protein folding. While it is apparent that sequence features such as transcriptional regulatory sequences are likely major determinants of where the template-switching events that yield recombination break points most commonly occur, it is evident that selection against misfolded recombinant proteins also strongly impacts observable recombination break-point distributions in coronavirus genomes sampled from nature.},
author = {{De Klerk}, Arne and Swanepoel, Phillip and Lourens, Rentia and Zondo, Mpumelelo and Abodunran, Isaac and Lytras, Spyros and MacLean, Oscar A. and Robertson, David and {Kosakovsky Pond}, Sergei L. and Zehr, Jordan D. and Kumar, Venkatesh and Stanhope, Michael J. and Harkins, Gordon and Murrell, Ben and Martin, Darren P.},
doi = {10.1093/VE/VEAC054},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/De Klerk et al. - 2022 - Conserved recombination patterns across coronavirus subgenera.pdf:pdf},
issn = {20571577},
journal = {Virus Evolution},
keywords = {Coronavirus,Evolution,OA,Phylogenetics,Recombination,Selection,genomics{\_}fund{\_}ack,original},
mendeley-tags = {OA,genomics{\_}fund{\_}ack,original},
month = {sep},
number = {2},
pages = {veac054},
pmid = {35814334},
publisher = {Oxford Academic},
title = {{Conserved recombination patterns across coronavirus subgenera}},
url = {https://academic.oup.com/ve/article/8/2/veac054/6608204},
volume = {8},
year = {2022}
}

Recombination contributes to the genetic diversity found in coronaviruses and is known to be a prominent mechanism whereby they evolve. It is apparent, both from controlled experiments and in genome sequences sampled from nature, that patterns of recombination in coronaviruses are non-random and that this is likely attributable to a combination of sequence features that favour the occurrence of recombination break points at specific genomic sites, and selection disfavouring the survival of recombinants within which favourable intra-genome interactions have been disrupted. Here we leverage available whole-genome sequence data for six coronavirus subgenera to identify specific patterns of recombination that are conserved between multiple subgenera and then identify the likely factors that underlie these conserved patterns. Specifically, we confirm the non-randomness of recombination break points across all six tested coronavirus subgenera, locate conserved recombination hot- and cold-spots, and determine that the locations of transcriptional regulatory sequences are likely major determinants of conserved recombination break-point hotspot locations. We find that while the locations of recombination break points are not uniformly associated with degrees of nucleotide sequence conservation, they display significant tendencies in multiple coronavirus subgenera to occur in low guanine-cytosine content genome regions, in non-coding regions, at the edges of genes, and at sites within the Spike gene that are predicted to be minimally disruptive of Spike protein folding. While it is apparent that sequence features such as transcriptional regulatory sequences are likely major determinants of where the template-switching events that yield recombination break points most commonly occur, it is evident that selection against misfolded recombinant proteins also strongly impacts observable recombination break-point distributions in coronavirus genomes sampled from nature.

@article{Viana2022,
abstract = {The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic in southern Africa has been characterised by three distinct waves. The first was associated with a mix of SARS-CoV-2 lineages, whilst the second and third waves were driven by the Beta and Delta variants, respectively. In November 2021, genomic surveillance teams in South Africa and Botswana detected a new SARS-CoV-2 variant associated with a rapid resurgence of infections in Gauteng Province, South Africa. Within three days of the first genome being uploaded, it was designated a variant of concern (Omicron) by the World Health Organization and, within three weeks, had been identified in 87 countries. The Omicron variant is exceptional for carrying over 30 mutations in the spike glycoprotein, predicted to influence antibody neutralization and spike function. Here, we describe the genomic profile and early transmission dynamics of Omicron, highlighting the rapid spread in regions with high levels of population immunity.},
author = {Viana, Raquel and Moyo, Sikhulile and Amoako, Daniel G and Tegally, Houriiyah and Scheepers, Cathrine and Althaus, Christian L and Anyaneji, Ugochukwu J and Bester, Phillip A and Boni, Maciej F. and Chand, Mohammed and Choga, Wonderful T. and Colquhoun, Rachel and Davids, Michaela and Deforche, Koen and Doolabh, Deelan and du Plessis, Louis and Engelbrecht, Susan and Everatt, Josie and Giandhari, Jennifer and Giovanetti, Marta and Hardie, Diana and Hill, Verity and Hsiao, Nei-Yuan and Iranzadeh, Arash and Ismail, Arshad and Joseph, Charity and Joseph, Rageema and Koopile, Legodile and {Kosakovsky Pond}, Sergei L. and Kraemer, Moritz U. G. and Kuate-Lere, Lesego and Laguda-Akingba, Oluwakemi and Lesetedi-Mafoko, Onalethatha and Lessells, Richard J. and Lockman, Shahin and Lucaci, Alexander G. and Maharaj, Arisha and Mahlangu, Boitshoko and Maponga, Tongai and Mahlakwane, Kamela and Makatini, Zinhle and Marais, Gert and Maruapula, Dorcas and Masupu, Kereng and Matshaba, Mogomotsi and Mayaphi, Simnikiwe and Mbhele, Nokuzola and Mbulawa, Mpaphi B. and Mendes, Adriano and Mlisana, Koleka and Mnguni, Anele and Mohale, Thabo and Moir, Monika and Moruisi, Kgomotso and Mosepele, Mosepele and Motsatsi, Gerald and Motswaledi, Modisa S. and Mphoyakgosi, Thongbotho and Msomi, Nokukhanya and Mwangi, Peter N. and Naidoo, Yeshnee and Ntuli, Noxolo and Nyaga, Martin and Olubayo, Lucier and Pillay, Sureshnee and Radibe, Botshelo and Ramphal, Yajna and Ramphal, Upasana and San, James E. and Scott, Lesley and Shapiro, Roger and Singh, Lavanya and Smith-Lawrence, Pamela and Stevens, Wendy and Strydom, Amy and Subramoney, Kathleen and Tebeila, Naume and Tshiabuila, Derek and Tsui, Joseph and van Wyk, Stephanie and Weaver, Steven and Wibmer, Constantinos K. and Wilkinson, Eduan and Wolter, Nicole and Zarebski, Alexander E. and Zuze, Boitumelo and Goedhals, Dominique and Preiser, Wolfgang and Treurnicht, Florette and Venter, Marietje and Williamson, Carolyn and Pybus, Oliver G. and Bhiman, Jinal and Glass, Allison and Martin, Darren P. and Rambaut, Andrew and Gaseitsiwe, Simani and von Gottberg, Anne and de Oliveira, Tulio},
doi = {10.1038/D41586-021-03832-5},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Viana et al. - 2022 - Rapid epidemic expansion of the SARS-CoV-2 Omicron variant in southern Africa.pdf:pdf},
issn = {0028-0836},
journal = {Nature},
keywords = {OA,fund{\_}ack,genomics{\_}fund{\_}ack,original},
mendeley-tags = {OA,fund{\_}ack,genomics{\_}fund{\_}ack,original},
month = {jan},
pages = {679--686},
pmid = {35042229},
title = {{Rapid epidemic expansion of the SARS-CoV-2 Omicron variant in southern Africa}},
url = {https://www.nature.com/articles/d41586-021-03832-5},
volume = {603},
year = {2022}
}

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic in southern Africa has been characterised by three distinct waves. The first was associated with a mix of SARS-CoV-2 lineages, whilst the second and third waves were driven by the Beta and Delta variants, respectively. In November 2021, genomic surveillance teams in South Africa and Botswana detected a new SARS-CoV-2 variant associated with a rapid resurgence of infections in Gauteng Province, South Africa. Within three days of the first genome being uploaded, it was designated a variant of concern (Omicron) by the World Health Organization and, within three weeks, had been identified in 87 countries. The Omicron variant is exceptional for carrying over 30 mutations in the spike glycoprotein, predicted to influence antibody neutralization and spike function. Here, we describe the genomic profile and early transmission dynamics of Omicron, highlighting the rapid spread in regions with high levels of population immunity.

@article{Hussey2022,
abstract = {Background Emerging data suggest that SARS-CoV-2 Omicron variant of concern (VOC)is associated with reduced risk of severe disease. The extent to which this reflects a difference in the inherent virulence of Omicron, or just higher levels of population immunity, is currently not clear. Methods RdRp target delay (RTD: a difference in cycle threshold value of RdRp - E {\textgreater} 3.5) in the Seegene AllplexTM 2019-nCoV PCR assay is a proxy marker for the Delta VOC. The absence of this proxy marker in the transition period was used to identify suspected Omicron VOC infections. Cox regression was performed for the outcome of hospital admission in those who tested positive for SARS-CoV-2 on the Seegene AllplexTM assay from 1 November to 14 December 2021 in the Western Cape Province, South Africa, public sector. Vaccination status at time of diagnosis, as well as prior diagnosed infection and comorbidities, were adjusted for. Results 150 cases with RTD (proxy for Delta) and 1486 cases without RTD (proxy for Omicron) were included. Cases without RTD had a lower hazard of admission (adjusted Hazard Ratio [aHR] of 0.56, 95{\%} confidence interval [CI] 0.34-0.91). Complete vaccination was protective of admission with an aHR of 0.45 (95{\%}CI 0.26-0.77). Conclusion Omicron has resulted in a lower risk of hospital admission, compared to contemporaneous Delta infection in the Western Cape Province, when using the proxy marker of RTD. Under-ascertainment of reinfections with an immune escape variant like Omicron remains a challenge to accurately assessing variant virulence. {\#}{\#}{\#} Competing Interest Statement The authors have declared no competing interest. {\#}{\#}{\#} Funding Statement This study was funded by the Grand Challenges ICODA pilot initiative delivered by Health Data Research UK and funded by the Bill {\&} Melinda Gates and the Minderoo Foundations (INV-017293), and by a research Flagship grant from the South African Medical Research Council. Additional support was provided by the Francis Crick Institute which receives its core funding from Cancer Research UK (FC0010218), the UK Medical Research Council (FC0010218), and the Wellcome Trust (FC0010218) as well as Wellcome (203135, 222574). {\#}{\#}{\#} Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study was approved by the University of Cape Town Research Ethics Committee (HREC 460/2020). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors.},
author = {Hussey, Hannah and Davies, Mary-Ann and Heekes, Alexa and Williamson, Carolyn and Valley-Omar, Ziyaad and Hardie, Diana Ruth and Korsman, Stephen and Doolabh, Deelan and Preiser, Wolfgang and Maponga, Tongai and Iranzadeh, Arash and Wasserman, Sean and Schreuder, Neshaad and Boloko, Linda and Symons, Greg and Raubenheimer, Peter and Viljoen, Braam and Solomon, Wesley and Rousseau, Petro and Parker, Arifa and Wolter, Nicole and Cohen, Cheryl and JASSAT, WAASILA and Lessels, Richard and Wilkinson, Robert J and Boulle, Andrew and Hsiao, Nei-yuan},
doi = {10.1101/2022.01.13.22269211},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Hussey et al. - 2022 - Assessing the clinical severity of the Omicron variant in the Western Cape Province, South Africa, using the diag.pdf:pdf},
journal = {medRxiv},
keywords = {OA,fund{\_}ack,genomics{\_}fund{\_}ack,original},
mendeley-tags = {OA,fund{\_}ack,genomics{\_}fund{\_}ack,original},
month = {jan},
pages = {2022.01.13.22269211},
publisher = {Cold Spring Harbor Laboratory Press},
title = {{Assessing the clinical severity of the Omicron variant in the Western Cape Province, South Africa, using the diagnostic PCR proxy marker of RdRp target delay to distinguish between Omicron and Delta infections: a survival analysis}},
url = {https://www.medrxiv.org/content/10.1101/2022.01.13.22269211v1 https://www.medrxiv.org/content/10.1101/2022.01.13.22269211v1.abstract},
year = {2022}
}

Background Emerging data suggest that SARS-CoV-2 Omicron variant of concern (VOC)is associated with reduced risk of severe disease. The extent to which this reflects a difference in the inherent virulence of Omicron, or just higher levels of population immunity, is currently not clear. Methods RdRp target delay (RTD: a difference in cycle threshold value of RdRp - E \textgreater 3.5) in the Seegene AllplexTM 2019-nCoV PCR assay is a proxy marker for the Delta VOC. The absence of this proxy marker in the transition period was used to identify suspected Omicron VOC infections. Cox regression was performed for the outcome of hospital admission in those who tested positive for SARS-CoV-2 on the Seegene AllplexTM assay from 1 November to 14 December 2021 in the Western Cape Province, South Africa, public sector. Vaccination status at time of diagnosis, as well as prior diagnosed infection and comorbidities, were adjusted for. Results 150 cases with RTD (proxy for Delta) and 1486 cases without RTD (proxy for Omicron) were included. Cases without RTD had a lower hazard of admission (adjusted Hazard Ratio [aHR] of 0.56, 95% confidence interval [CI] 0.34-0.91). Complete vaccination was protective of admission with an aHR of 0.45 (95%CI 0.26-0.77). Conclusion Omicron has resulted in a lower risk of hospital admission, compared to contemporaneous Delta infection in the Western Cape Province, when using the proxy marker of RTD. Under-ascertainment of reinfections with an immune escape variant like Omicron remains a challenge to accurately assessing variant virulence. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study was funded by the Grand Challenges ICODA pilot initiative delivered by Health Data Research UK and funded by the Bill & Melinda Gates and the Minderoo Foundations (INV-017293), and by a research Flagship grant from the South African Medical Research Council. Additional support was provided by the Francis Crick Institute which receives its core funding from Cancer Research UK (FC0010218), the UK Medical Research Council (FC0010218), and the Wellcome Trust (FC0010218) as well as Wellcome (203135, 222574). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study was approved by the University of Cape Town Research Ethics Committee (HREC 460/2020). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors.

@article{Valley-Omar2022,
abstract = {Routine SARS-CoV-2 surveillance in the Western Cape region of South Africa (January-August 2021) found a reduced RT-PCR amplification efficiency of the RdRp-gene target of the Seegene, Allplex 2019-nCoV diagnostic assay from June 2021 when detecting the Delta variant. We investigated whether the reduced amplification efficiency denoted by an increased RT-PCR cycle threshold value (R$\Delta$E) can be used as an indirect measure of SARS-CoV-2 Delta variant prevalence. We found a significant increase in the median R$\Delta$E for patient samples tested from June 2021, which coincided with the emergence of the SARS-CoV-2 Delta variant within our sample set. Whole genome sequencing on a subset of patient samples identified a highly conserved G15451A, non-synonymous mutation exclusively within the RdRp gene of Delta variants, which may cause reduced RT-PCR amplification efficiency. While whole genome sequencing plays an important in identifying novel SARS-CoV-2 variants, monitoring R$\Delta$E value can serve as a useful surrogate for rapid tracking of Delta variant prevalence.},
author = {Valley-Omar, Ziyaad and Marais, Gert and Iranzadeh, Arash and Naidoo, Michelle and Korsman, Stephen and Maponga, Tongai and Hussey, Hannah and Davies, Mary-Ann and Boulle, Andrew and Doolabh, Deelan and Laubscher, Mariska and Wojno, Justyna and Deetlefs, J.D. and Maritz, Jean and Scott, Lesley and Msomi, Nokukhanya and Naicker, Cherise and Tegally, Houriiyah and de Oliveira, Tulio and Bhiman, Jinal and Williamson, Carolyn and Preiser, Wolfgang and Hardie, Diana and Hsiao, Nei-yuan},
doi = {10.1016/j.jviromet.2022.114471},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Valley-Omar et al. - 2022 - Reduced amplification efficiency of the RNA-dependent-RNA-polymerase target enables tracking of the Delta SA.pdf:pdf},
issn = {01660934},
journal = {Journal of Virological Methods},
keywords = {OA,fund{\_}ack,genomics{\_}fund{\_}ack,original},
mendeley-tags = {OA,fund{\_}ack,genomics{\_}fund{\_}ack,original},
month = {apr},
pages = {114471},
pmid = {35051442},
publisher = {Elsevier},
title = {{Reduced amplification efficiency of the RNA-dependent-RNA-polymerase target enables tracking of the Delta SARS-CoV-2 variant using routine diagnostic tests}},
url = {https://linkinghub.elsevier.com/retrieve/pii/S0166093422000180},
volume = {302},
year = {2022}
}

Routine SARS-CoV-2 surveillance in the Western Cape region of South Africa (January-August 2021) found a reduced RT-PCR amplification efficiency of the RdRp-gene target of the Seegene, Allplex 2019-nCoV diagnostic assay from June 2021 when detecting the Delta variant. We investigated whether the reduced amplification efficiency denoted by an increased RT-PCR cycle threshold value (R$Δ$E) can be used as an indirect measure of SARS-CoV-2 Delta variant prevalence. We found a significant increase in the median R$Δ$E for patient samples tested from June 2021, which coincided with the emergence of the SARS-CoV-2 Delta variant within our sample set. Whole genome sequencing on a subset of patient samples identified a highly conserved G15451A, non-synonymous mutation exclusively within the RdRp gene of Delta variants, which may cause reduced RT-PCR amplification efficiency. While whole genome sequencing plays an important in identifying novel SARS-CoV-2 variants, monitoring R$Δ$E value can serve as a useful surrogate for rapid tracking of Delta variant prevalence.

@article{Fendler2022,
abstract = {Summary Patients with blood cancer continue to have a greater risk of inadequate immune responses following three COVID-19 vaccine doses and risk of severe COVID-19 disease. In the context of the CAPTURE study (NCT03226886), we report immune responses in 80 patients with blood cancer who received a fourth dose of BNT162b2. We measured neutralizing antibody titers (NAbTs) using a live virus microneutralization assay against wild-type (WT), Delta, and Omicron BA.1 and BA.2 and T cell responses against WT and Omicron BA.1 using an activation-induced marker (AIM) assay. The proportion of patients with detectable NAb titers and T cell responses after the fourth vaccine dose increased compared with that after the third vaccine dose. Patients who received B cell-depleting therapies within the 12 months before vaccination have the greatest risk of not having detectable NAbT. In addition, we report immune responses in 57 patients with breakthrough infections after vaccination.},
author = {Fendler, Annika and Shepherd, Scott T C and Au, Lewis and Wu, Mary and Harvey, Ruth and Wilkinson, Katalin A and Schmitt, Andreas M and Tippu, Zayd and Shum, Benjamin and Farag, Sheima and Rogiers, Aljosja and Carlyle, Eleanor and Edmonds, Kim and {Del Rosario}, Lyra and Lingard, Karla and Mangwende, Mary and Holt, Lucy and Ahmod, Hamid and Korteweg, Justine and Foley, Tara and Barber, Taja and Emslie-Henry, Andrea and Caulfield-Lynch, Niamh and Byrne, Fiona and Deng, Daqi and Kjaer, Svend and Song, Ok-Ryul and Queval, Christophe J and Kavanagh, Caitlin and Wall, Emma C and Carr, Edward J and Caidan, Simon and Gavrielides, Mike and MacRae, James I and Kelly, Gavin and Peat, Kema and Kelly, Denise and Murra, Aida and Kelly, Kayleigh and O'Flaherty, Molly and Shea, Robyn L and Gardner, Gail and Murray, Darren and Popat, Sanjay and Yousaf, Nadia and Jhanji, Shaman and Tatham, Kate and Cunningham, David and {Van As}, Nicholas and Young, Kate and Furness, Andrew J S and Pickering, Lisa and Beale, Rupert and Swanton, Charles and Gandhi, Sonia and Gamblin, Steve and Bauer, David L V and Kassiotis, George and Howell, Michael and Nicholson, Emma and Walker, Susanna and Wilkinson, Robert J and Larkin, James and Turajlic, Samra},
doi = {10.1016/j.xcrm.2022.100781},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Fendler et al. - 2022 - Functional immune responses against SARS-CoV-2 variants of concern after fourth COVID-19 vaccine dose or infecti.pdf:pdf},
issn = {26663791},
journal = {Cell Reports Medicine},
keywords = {COVID-19,OA,SARS-CoV-2,T cells,blood cancer,fund{\_}ack,genomics{\_}fund{\_}ack,neutralizing antibodies,original,variants of concern},
mendeley-tags = {OA,fund{\_}ack,genomics{\_}fund{\_}ack,original},
month = {oct},
number = {10},
pages = {100781},
pmid = {36240755},
publisher = {Elsevier BV},
title = {{Functional immune responses against SARS-CoV-2 variants of concern after fourth COVID-19 vaccine dose or infection in patients with blood cancer}},
url = {http://www.cell.com/article/S2666379122003366/fulltext http://www.cell.com/article/S2666379122003366/abstract https://www.cell.com/cell-reports-medicine/abstract/S2666-3791(22)00336-6},
volume = {3},
year = {2022}
}

Summary Patients with blood cancer continue to have a greater risk of inadequate immune responses following three COVID-19 vaccine doses and risk of severe COVID-19 disease. In the context of the CAPTURE study (NCT03226886), we report immune responses in 80 patients with blood cancer who received a fourth dose of BNT162b2. We measured neutralizing antibody titers (NAbTs) using a live virus microneutralization assay against wild-type (WT), Delta, and Omicron BA.1 and BA.2 and T cell responses against WT and Omicron BA.1 using an activation-induced marker (AIM) assay. The proportion of patients with detectable NAb titers and T cell responses after the fourth vaccine dose increased compared with that after the third vaccine dose. Patients who received B cell-depleting therapies within the 12 months before vaccination have the greatest risk of not having detectable NAbT. In addition, we report immune responses in 57 patients with breakthrough infections after vaccination.

@article{Keeton2022,
abstract = {The SARS-CoV-2 Omicron variant has multiple Spike (S) protein mutations1,2 that contribute to escape from antibody neutralization3–6 and reduce vaccine protection from infection7,8. The extent to which other components of the adaptive response such as T cells may still target Omicron and contribute to protection from severe outcomes is unknown. We assessed the ability of T cells to react with Omicron spike in participants who were vaccinated with Ad26.CoV2.S, BNT162b2, or unvaccinated convalescent COVID-19 patients (n=70). We found that 70-80{\%} of the CD4+ and CD8+ T cell response to spike was maintained across study groups. Moreover, the magnitude of Omicron cross-reactive T cells was similar to Beta and Delta variants, despite Omicron harboring considerably more mutations. In Omicron-infected hospitalized patients (n=19), there were comparable T cell responses to ancestral spike, nucleocapsid and membrane proteins to those patients hospitalized in previous waves dominated by the ancestral, Beta or Delta variants (n=49). Thus, despite Omicron's extensive mutations and reduced susceptibility to neutralizing antibodies, the majority of T cell responses, induced by vaccination or infection, cross-recognize the variant. It remains to be determined whether well-preserved T cell immunity to Omicron contributes to protection from severe COVID-19, and is linked to early clinical observations from South Africa and elsewhere9–12.},
author = {Keeton, Roanne and Tincho, Marius B and Ngomti, Amkele and Baguma, Richard and Benede, Ntombi and Suzuki, Akiko and Khan, Khadija and Cele, Sandile and Bernstein, Mallory and Karim, Farina and Madzorera, Sharon V and Moyo-Gwete, Thandeka and Mennen, Mathilda and Skelem, Sango and Adriaanse, Marguerite and Mutithu, Daniel and Aremu, Olukayode and Stek, Cari and du Bruyn, Elsa and {Van Der Mescht}, Mieke A and de Beer, Zelda and de Villiers, Talita R and Bodenstein, Annie and van den Berg, Gretha and Mendes, Adriano and Strydom, Amy and Venter, Marietjie and Giandhari, Jennifer and Naidoo, Yeshnee and Pillay, Sureshnee and Tegally, Houriiyah and Grifoni, Alba and Weiskopf, Daniela and Sette, Alessandro and Wilkinson, Robert J and de Oliveira, Tulio and Bekker, Linda-Gail and Gray, Glenda and Ueckermann, Veronica and Rossouw, Theresa and Boswell, Michael T and Bihman, Jinal and Moore, Penny L and Sigal, Alex and Ntusi, Ntobeko A B and Burgers, Wendy A and Riou, Catherine},
doi = {10.1038/s41586-022-04460-3},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Keeton et al. - 2022 - T cell responses to SARS-CoV-2 spike cross-recognize Omicron.pdf:pdf},
issn = {1476-4687},
journal = {Nature},
keywords = {2,CoV,Lymphocyte activation,OA,SARS,Viral infection,fund{\_}ack,genomics{\_}fund{\_}ack,original},
mendeley-tags = {OA,fund{\_}ack,genomics{\_}fund{\_}ack,original},
month = {jan},
pages = {488--492},
pmid = {35102311},
publisher = {Nature Publishing Group},
title = {{T cell responses to SARS-CoV-2 spike cross-recognize Omicron}},
url = {https://www.nature.com/articles/s41586-022-04460-3},
volume = {603},
year = {2022}
}

The SARS-CoV-2 Omicron variant has multiple Spike (S) protein mutations1,2 that contribute to escape from antibody neutralization3–6 and reduce vaccine protection from infection7,8. The extent to which other components of the adaptive response such as T cells may still target Omicron and contribute to protection from severe outcomes is unknown. We assessed the ability of T cells to react with Omicron spike in participants who were vaccinated with Ad26.CoV2.S, BNT162b2, or unvaccinated convalescent COVID-19 patients (n=70). We found that 70-80% of the CD4+ and CD8+ T cell response to spike was maintained across study groups. Moreover, the magnitude of Omicron cross-reactive T cells was similar to Beta and Delta variants, despite Omicron harboring considerably more mutations. In Omicron-infected hospitalized patients (n=19), there were comparable T cell responses to ancestral spike, nucleocapsid and membrane proteins to those patients hospitalized in previous waves dominated by the ancestral, Beta or Delta variants (n=49). Thus, despite Omicron's extensive mutations and reduced susceptibility to neutralizing antibodies, the majority of T cell responses, induced by vaccination or infection, cross-recognize the variant. It remains to be determined whether well-preserved T cell immunity to Omicron contributes to protection from severe COVID-19, and is linked to early clinical observations from South Africa and elsewhere9–12.

@article{Keeton2022a,
abstract = {Multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exposures, from infection or vaccination, can potently boost spike antibody responses. Less is known about the impact of repeated exposures on T cell responses. Here, we compare the prevalence and frequency of peripheral SARS-CoV-2-specific T cell and immunoglobulin G (IgG) responses in 190 individuals with complex SARS-CoV-2 exposure histories. As expected, an increasing number of SARS-CoV-2 spike exposures significantly enhances the magnitude of IgG responses, while repeated exposures improve the number of T cell responders but have less impact on SARS-CoV-2 spike-specific T cell frequencies in the circulation. Moreover, we find that the number and nature of exposures (rather than the order of infection and vaccination) shape the spike immune response, with spike-specific CD4 T cells displaying a greater polyfunctional potential following hybrid immunity compared with vaccination only. Characterizing adaptive immunity from an evolving viral and immunological landscape may inform vaccine strategies to elicit optimal immunity as the pandemic progress.},
author = {Keeton, Roanne and Tincho, Marius B and Suzuki, Akiko and Benede, Ntombi and Ngomti, Amkele and Baguma, Richard and Chauke, Masego V and Mennen, Mathilda and Skelem, Sango and Adriaanse, Marguerite and Grifoni, Alba and Weiskopf, Daniela and Sette, Alessandro and Bekker, Linda Gail and Gray, Glenda and Ntusi, Ntobeko A B and Burgers, Wendy A and Riou, Catherine},
doi = {10.1016/J.XCRM.2022.100898},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Keeton et al. - 2022 - Impact of SARS-CoV-2 exposure history on the T cell and IgG response.pdf:pdf},
issn = {2666-3791},
journal = {Cell Reports Medicine},
keywords = {Ad26.COV2.S vaccine,COVID-19,IgG response,OA,OA{\_}PMC,SARS-CoV-2,T cell response,fund{\_}ack,genomics{\_}fund{\_}ack,hybrid immunity,original},
mendeley-tags = {OA,OA{\_}PMC,fund{\_}ack,genomics{\_}fund{\_}ack,original},
month = {dec},
pages = {100898},
pmid = {36584684},
publisher = {Cell Press},
title = {{Impact of SARS-CoV-2 exposure history on the T cell and IgG response}},
year = {2022}
}

Multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exposures, from infection or vaccination, can potently boost spike antibody responses. Less is known about the impact of repeated exposures on T cell responses. Here, we compare the prevalence and frequency of peripheral SARS-CoV-2-specific T cell and immunoglobulin G (IgG) responses in 190 individuals with complex SARS-CoV-2 exposure histories. As expected, an increasing number of SARS-CoV-2 spike exposures significantly enhances the magnitude of IgG responses, while repeated exposures improve the number of T cell responders but have less impact on SARS-CoV-2 spike-specific T cell frequencies in the circulation. Moreover, we find that the number and nature of exposures (rather than the order of infection and vaccination) shape the spike immune response, with spike-specific CD4 T cells displaying a greater polyfunctional potential following hybrid immunity compared with vaccination only. Characterizing adaptive immunity from an evolving viral and immunological landscape may inform vaccine strategies to elicit optimal immunity as the pandemic progress.

@article{Sheward2022,
abstract = {Despite being the focus of extensive research, we still do not know how to reproducibly elicit cross-neutralizing antibodies against variable pathogens by vaccination. Here, we characterize the ant...},
author = {Sheward, Daniel J and Hermanus, Tandile and Murrell, Ben and Garrett, Nigel and Karim, Salim S Abdool and Morris, Lynn and Moore, Penny L and Williamson, Carolyn},
doi = {10.1128/JVI.00324-22},
editor = {Silvestri, Guido},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Sheward et al. - 2022 - HIV coinfection provides insights for the design of vaccine cocktails to elicit broadly neutralizing antibodies.pdf:pdf},
issn = {0022-538X},
journal = {Journal of Virology},
keywords = {OA,broadly neutralizing antibodies,coinfection,fund{\_}ack,genomics{\_}fund{\_}ack,human immunodeficiency virus,neutralizing antibodies,original,vaccine cocktails,vaccines},
mendeley-tags = {OA,fund{\_}ack,genomics{\_}fund{\_}ack,original},
month = {jun},
number = {14},
pages = {e00324--22},
pmid = {35758668},
publisher = {American Society for Microbiology 1752 N St., N.W., Washington, DC},
title = {{HIV coinfection provides insights for the design of vaccine cocktails to elicit broadly neutralizing antibodies}},
url = {https://journals.asm.org/doi/10.1128/jvi.00324-22},
volume = {96},
year = {2022}
}

Despite being the focus of extensive research, we still do not know how to reproducibly elicit cross-neutralizing antibodies against variable pathogens by vaccination. Here, we characterize the ant...

@article{Kassanjee2022,
abstract = {Introduction: While a large proportion of people with HIV (PWH) have experienced SARS-CoV-2 infections, there is uncertainty about the role of HIV disease severity on COVID-19 outcomes, especially in lower income settings. We studied the association between mortality and characteristics of HIV severity and management, and vaccination, among adult PWH. Methods: We analysed observational cohort data on all PWH aged ≥15 years experiencing a diagnosed SARS-CoV-2 infection (until March 2022), who accessed public sector healthcare in the Western Cape province of South Africa. Logistic regression was used to study the association of mortality with CD4 cell count, viral load, evidence of ART, time since first HIV evidence, and vaccination, adjusting for demographic characteristics, comorbidities, admission pressure, location and time period. Results: Mortality occurred in 5.7{\%} (95{\%} CI: 5.3,6.0) of 17 831 first diagnosed infections. Higher mortality was associated with lower recent CD4, no evidence of ART collection, high or unknown recent viral load (among those with ART evidence), and recent first HIV evidence, differentially by age. Vaccination was protective. The burden of comorbidities was high, and tuberculosis, chronic kidney disease, diabetes and hypertension were associated with higher mortality, more strongly in younger adults. Conclusions: Mortality was strongly associated with suboptimal HIV control, and prevalence of these risk factors increased in later COVID-19 waves. It remains a public health priority to ensure PWH are on suppressive ART and vaccinated, and manage any disruptions in care that occurred during the pandemic. The diagnosis and management of comorbidities, including for tuberculosis, should be optimised. {\#}{\#}{\#} Competing Interest Statement The authors have declared no competing interest. {\#}{\#}{\#} Funding Statement We acknowledge funding for the Western Cape Provincial Health Data Centre from the Western Cape Department of Health, the US National Institutes for Health (R01 HD080465, U01 AI069924), the Bill and Melinda Gates Foundation (1164272, 1191327), the United States Agency for International Development (72067418CA00023), the European Union (101045989) and the Grand Challenges ICODA pilot initiative delivered by Health Data Research UK and funded by the Bill {\&} Melinda Gates and Minderoo Foundations (INV-017293). Funding was also received from Wellcome Trust (203135/Z/16/Z, 222574). The funders had no role in the study design, data collection, data analysis, data interpretation, or writing of this report. The opinions, findings and conclusions expressed in this manuscript reflect those of the authors alone. {\#}{\#}{\#} Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The Health Research Ethics committee of the University of Cape Town, and the Western Cape Government Provincial Department of Health, gave ethical approval for this work I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes The data are not publicly available due to privacy or ethical restrictions. The data that support the findings of this study can be requested from the Western Cape Provincial Health Data Centre (WCPHDC) [https://www.westerncape.gov.za/general-publication/provincial-health-data-centre]; restrictions apply to the availability of these data.},
author = {Kassanjee, Reshma and Davies, Mary-Ann and Ngwenya, Olina and Osei-Yeboah, Richard and Jacobs, Theuns and Morden, Erna and Timmerman, Venessa and Britz, Stefan and Mendelson, Marc and Taljaard, Jantjie and Riou, Julien and Boulle, Andrew and Tiffin, Nicki and Zinyakatira, Nesbert},
doi = {10.1101/2022.10.17.22281085},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Kassanjee et al. - 2022 - COVID-19 among adults living with HIV Correlates of mortality in a general population in a resource-limited se.pdf:pdf},
isbn = {10.1101/2022.10.1},
journal = {medRxiv},
keywords = {OA,fund{\_}ack,genomics{\_}fund{\_}ack,original},
mendeley-tags = {OA,fund{\_}ack,genomics{\_}fund{\_}ack,original},
month = {oct},
pages = {2022.10.17.22281085},
publisher = {Cold Spring Harbor Laboratory Press},
title = {{COVID-19 among adults living with HIV: Correlates of mortality in a general population in a resource-limited setting}},
url = {https://www.medrxiv.org/content/10.1101/2022.10.17.22281085v1 https://www.medrxiv.org/content/10.1101/2022.10.17.22281085v1.abstract},
year = {2022}
}

Introduction: While a large proportion of people with HIV (PWH) have experienced SARS-CoV-2 infections, there is uncertainty about the role of HIV disease severity on COVID-19 outcomes, especially in lower income settings. We studied the association between mortality and characteristics of HIV severity and management, and vaccination, among adult PWH. Methods: We analysed observational cohort data on all PWH aged ≥15 years experiencing a diagnosed SARS-CoV-2 infection (until March 2022), who accessed public sector healthcare in the Western Cape province of South Africa. Logistic regression was used to study the association of mortality with CD4 cell count, viral load, evidence of ART, time since first HIV evidence, and vaccination, adjusting for demographic characteristics, comorbidities, admission pressure, location and time period. Results: Mortality occurred in 5.7% (95% CI: 5.3,6.0) of 17 831 first diagnosed infections. Higher mortality was associated with lower recent CD4, no evidence of ART collection, high or unknown recent viral load (among those with ART evidence), and recent first HIV evidence, differentially by age. Vaccination was protective. The burden of comorbidities was high, and tuberculosis, chronic kidney disease, diabetes and hypertension were associated with higher mortality, more strongly in younger adults. Conclusions: Mortality was strongly associated with suboptimal HIV control, and prevalence of these risk factors increased in later COVID-19 waves. It remains a public health priority to ensure PWH are on suppressive ART and vaccinated, and manage any disruptions in care that occurred during the pandemic. The diagnosis and management of comorbidities, including for tuberculosis, should be optimised. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement We acknowledge funding for the Western Cape Provincial Health Data Centre from the Western Cape Department of Health, the US National Institutes for Health (R01 HD080465, U01 AI069924), the Bill and Melinda Gates Foundation (1164272, 1191327), the United States Agency for International Development (72067418CA00023), the European Union (101045989) and the Grand Challenges ICODA pilot initiative delivered by Health Data Research UK and funded by the Bill & Melinda Gates and Minderoo Foundations (INV-017293). Funding was also received from Wellcome Trust (203135/Z/16/Z, 222574). The funders had no role in the study design, data collection, data analysis, data interpretation, or writing of this report. The opinions, findings and conclusions expressed in this manuscript reflect those of the authors alone. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The Health Research Ethics committee of the University of Cape Town, and the Western Cape Government Provincial Department of Health, gave ethical approval for this work I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes The data are not publicly available due to privacy or ethical restrictions. The data that support the findings of this study can be requested from the Western Cape Provincial Health Data Centre (WCPHDC) [https://www.westerncape.gov.za/general-publication/provincial-health-data-centre]; restrictions apply to the availability of these data.

@article{Wolter2022,
abstract = {Summary Background The SARS-CoV-2 omicron variant of concern was identified in South Africa in November, 2021, and was associated with an increase in COVID-19 cases. We aimed to assess the clinical severity of infections with the omicron variant using S gene target failure (SGTF) on the Thermo Fisher Scientific TaqPath COVID-19 PCR test as a proxy. Methods We did data linkages for national, South African COVID-19 case data, SARS-CoV-2 laboratory test data, SARS-CoV-2 genome data, and COVID-19 hospital admissions data. For individuals diagnosed with COVID-19 via TaqPath PCR tests, infections were designated as either SGTF or non-SGTF. The delta variant was identified by genome sequencing. Using multivariable logistic regression models, we assessed disease severity and hospitalisations by comparing individuals with SGTF versus non-SGTF infections diagnosed between Oct 1 and Nov 30, 2021, and we further assessed disease severity by comparing SGTF-infected individuals diagnosed between Oct 1 and Nov 30, 2021, with delta variant-infected individuals diagnosed between April 1 and Nov 9, 2021. Findings From Oct 1 (week 39), 2021, to Dec 6 (week 49), 2021, 161 328 cases of COVID-19 were reported in South Africa. 38 282 people were diagnosed via TaqPath PCR tests and 29 721 SGTF infections and 1412 non-SGTF infections were identified. The proportion of SGTF infections increased from two (3{\textperiodcentered}2{\%}) of 63 in week 39 to 21 978 (97{\textperiodcentered}9{\%}) of 22 455 in week 48. After controlling for factors associated with hospitalisation, individuals with SGTF infections had significantly lower odds of admission than did those with non-SGTF infections (256 [2{\textperiodcentered}4{\%}] of 10 547 vs 121 [12{\textperiodcentered}8{\%}] of 948; adjusted odds ratio [aOR] 0{\textperiodcentered}2, 95{\%} CI 0{\textperiodcentered}1–0{\textperiodcentered}3). After controlling for factors associated with disease severity, the odds of severe disease were similar between hospitalised individuals with SGTF versus non-SGTF infections (42 [21{\%}] of 204 vs 45 [40{\%}] of 113; aOR 0{\textperiodcentered}7, 95{\%} CI 0{\textperiodcentered}3–1{\textperiodcentered}4). Compared with individuals with earlier delta variant infections, SGTF-infected individuals had a significantly lower odds of severe disease (496 [62{\textperiodcentered}5{\%}] of 793 vs 57 [23{\textperiodcentered}4{\%}] of 244; aOR 0{\textperiodcentered}3, 95{\%} CI 0{\textperiodcentered}2–0{\textperiodcentered}5), after controlling for factors associated with disease severity. Interpretation Our early analyses suggest a significantly reduced odds of hospitalisation among individuals with SGTF versus non-SGTF infections diagnosed during the same time period. SGTF-infected individuals had a significantly reduced odds of severe disease compared with individuals infected earlier with the delta variant. Some of this reduced severity is probably a result of previous immunity. Funding The South African Medical Research Council, the South African National Department of Health, US Centers for Disease Control and Prevention, the African Society of Laboratory Medicine, Africa Centers for Disease Control and Prevention, the Bill {\&} Melinda Gates Foundation, the Wellcome Trust, and the Fleming Fund.},
author = {Wolter, Nicole and Jassat, Waasila and Walaza, Sibongile and Welch, Richard and Moultrie, Harry and Groome, Michelle and Amoako, Daniel Gyamfi and Everatt, Josie and Bhiman, Jinal N and Scheepers, Cathrine and Tebeila, Naume and Chiwandire, Nicola and du Plessis, Mignon and Govender, Nevashan and Ismail, Arshad and Glass, Allison and Mlisana, Koleka and Stevens, Wendy and Treurnicht, Florette K and Makatini, Zinhle and Hsiao, Nei-yuan and Parboosing, Raveen and Wadula, Jeannette and Hussey, Hannah and Davies, Mary-Ann and Boulle, Andrew and von Gottberg, Anne and Cohen, Cheryl},
doi = {10.1016/S0140-6736(22)00017-4},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Wolter et al. - 2022 - Early assessment of the clinical severity of the SARS-CoV-2 omicron variant in South Africa a data linkage study.pdf:pdf},
issn = {0140-6736},
journal = {The Lancet},
keywords = {OA,fund{\_}ack,genomics{\_}fund{\_}ack,original},
mendeley-tags = {OA,fund{\_}ack,genomics{\_}fund{\_}ack,original},
month = {jan},
number = {10323},
pages = {437--446},
pmid = {35065011},
publisher = {Elsevier},
title = {{Early assessment of the clinical severity of the SARS-CoV-2 omicron variant in South Africa: a data linkage study}},
url = {http://www.thelancet.com/article/S0140673622000174/fulltext http://www.thelancet.com/article/S0140673622000174/abstract https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(22)00017-4/abstract},
volume = {399},
year = {2022}
}

Summary Background The SARS-CoV-2 omicron variant of concern was identified in South Africa in November, 2021, and was associated with an increase in COVID-19 cases. We aimed to assess the clinical severity of infections with the omicron variant using S gene target failure (SGTF) on the Thermo Fisher Scientific TaqPath COVID-19 PCR test as a proxy. Methods We did data linkages for national, South African COVID-19 case data, SARS-CoV-2 laboratory test data, SARS-CoV-2 genome data, and COVID-19 hospital admissions data. For individuals diagnosed with COVID-19 via TaqPath PCR tests, infections were designated as either SGTF or non-SGTF. The delta variant was identified by genome sequencing. Using multivariable logistic regression models, we assessed disease severity and hospitalisations by comparing individuals with SGTF versus non-SGTF infections diagnosed between Oct 1 and Nov 30, 2021, and we further assessed disease severity by comparing SGTF-infected individuals diagnosed between Oct 1 and Nov 30, 2021, with delta variant-infected individuals diagnosed between April 1 and Nov 9, 2021. Findings From Oct 1 (week 39), 2021, to Dec 6 (week 49), 2021, 161 328 cases of COVID-19 were reported in South Africa. 38 282 people were diagnosed via TaqPath PCR tests and 29 721 SGTF infections and 1412 non-SGTF infections were identified. The proportion of SGTF infections increased from two (3˙2%) of 63 in week 39 to 21 978 (97˙9%) of 22 455 in week 48. After controlling for factors associated with hospitalisation, individuals with SGTF infections had significantly lower odds of admission than did those with non-SGTF infections (256 [2˙4%] of 10 547 vs 121 [12˙8%] of 948; adjusted odds ratio [aOR] 0˙2, 95% CI 0˙1–0˙3). After controlling for factors associated with disease severity, the odds of severe disease were similar between hospitalised individuals with SGTF versus non-SGTF infections (42 [21%] of 204 vs 45 [40%] of 113; aOR 0˙7, 95% CI 0˙3–1˙4). Compared with individuals with earlier delta variant infections, SGTF-infected individuals had a significantly lower odds of severe disease (496 [62˙5%] of 793 vs 57 [23˙4%] of 244; aOR 0˙3, 95% CI 0˙2–0˙5), after controlling for factors associated with disease severity. Interpretation Our early analyses suggest a significantly reduced odds of hospitalisation among individuals with SGTF versus non-SGTF infections diagnosed during the same time period. SGTF-infected individuals had a significantly reduced odds of severe disease compared with individuals infected earlier with the delta variant. Some of this reduced severity is probably a result of previous immunity. Funding The South African Medical Research Council, the South African National Department of Health, US Centers for Disease Control and Prevention, the African Society of Laboratory Medicine, Africa Centers for Disease Control and Prevention, the Bill & Melinda Gates Foundation, the Wellcome Trust, and the Fleming Fund.

@article{Lucaci2022,
abstract = {An important component of efforts to manage the ongoing COVID19 pandemic is the Rapid Assessment of how natural selection contributes to the emergence and proliferation of potentially dangerous SARS-CoV-2 lineages and CLades (RASCL). The RASCL pipeline enables continuous comparative phylogenetics-based selection analyses of rapidly growing clade-focused genome surveillance datasets, such as those produced following the initial detection of potentially dangerous variants. From such datasets RASCL automatically generates down-sampled codon alignments of individual genes/ORFs containing contextualizing background reference sequences, analyzes these with a battery of selection tests, and outputs results as both machine readable JSON files, and interactive notebook-based visualizations. Availability RASCL is available from a dedicated repository at {\textless}https://github.com/veg/RASCL{\textgreater} and as a Galaxy workflow {\textless}https://usegalaxy.eu/u/hyphy/w/rascl{\textgreater}. Existing clade/variant analysis results are available here: {\textless}https://observablehq.com/@aglucaci/rascl{\textgreater}. Contact Dr. Sergei L Kosakovsky Pond (spond{\{}at{\}}temple.edu). Supplementary information N/A {\#}{\#}{\#} Competing Interest Statement The authors have declared no competing interest.},
author = {Lucaci, Alexander G and Zehr, Jordan D and Shank, Stephen D and Bouvier, Dave and Mei, Han and Nekrutenko, Anton and Martin, Darren P and Pond, Sergei L Kosakovsky},
doi = {10.1101/2022.01.15.476448},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Lucaci et al. - 2022 - RASCL rapid assessment of SARS-CoV-2 clades through molecular sequence analysis.pdf:pdf},
journal = {bioRxiv},
keywords = {OA,genomics{\_}fund{\_}ack,original},
mendeley-tags = {OA,genomics{\_}fund{\_}ack,original},
month = {jan},
pages = {2022.01.15.476448},
pmid = {35075458},
publisher = {Cold Spring Harbor Laboratory},
title = {{RASCL: rapid assessment of SARS-CoV-2 clades through molecular sequence analysis}},
url = {https://www.biorxiv.org/content/10.1101/2022.01.15.476448v1 https://www.biorxiv.org/content/10.1101/2022.01.15.476448v1.abstract},
year = {2022}
}

An important component of efforts to manage the ongoing COVID19 pandemic is the Rapid Assessment of how natural selection contributes to the emergence and proliferation of potentially dangerous SARS-CoV-2 lineages and CLades (RASCL). The RASCL pipeline enables continuous comparative phylogenetics-based selection analyses of rapidly growing clade-focused genome surveillance datasets, such as those produced following the initial detection of potentially dangerous variants. From such datasets RASCL automatically generates down-sampled codon alignments of individual genes/ORFs containing contextualizing background reference sequences, analyzes these with a battery of selection tests, and outputs results as both machine readable JSON files, and interactive notebook-based visualizations. Availability RASCL is available from a dedicated repository at \textlesshttps://github.com/veg/RASCL\textgreater and as a Galaxy workflow \textlesshttps://usegalaxy.eu/u/hyphy/w/rascl\textgreater. Existing clade/variant analysis results are available here: \textlesshttps://observablehq.com/@aglucaci/rascl\textgreater. Contact Dr. Sergei L Kosakovsky Pond (spond\at\temple.edu). Supplementary information N/A ### Competing Interest Statement The authors have declared no competing interest.

@article{Wolter2022a,
abstract = {Early data indicated that infection with Omicron BA.1 sub-lineage was associated with a lower risk of hospitalisation and severe illness, compared to Delta infection. Recently, the BA.2 sub-lineage has increased in many areas globally. We aimed to assess the severity of BA.2 infections compared to BA.1 in South Africa. We performed data linkages for (i) national COVID-19 case data, (ii) SARS-CoV-2 laboratory test data, and (iii) COVID-19 hospitalisations data, nationally. For cases identified using TaqPath COVID-19 PCR, infections were designated as S-gene target failure (SGTF, proxy for BA.1) or S-gene positive (proxy for BA.2). Disease severity was assessed using multivariable logistic regression models comparing individuals with S-gene positive infection to SGTF-infected individuals diagnosed between 1 December 2021 to 20 January 2022. From week 49 (starting 5 December 2021) through week 4 (ending 29 January 2022), the proportion of S-gene positive infections increased from 3{\%} (931/31,271) to 80{\%} (2,425/3,031). The odds of being admitted to hospital did not differ between individuals with S-gene positive (BA.2 proxy) infection compared to SGTF (BA.1 proxy) infection (adjusted odds ratio (aOR) 0.96, 95{\%} confidence interval (CI) 0.85-1.09). Among hospitalised individuals, after controlling for factors associated with severe disease, the odds of severe disease did not differ for individuals with S-gene positive infection compared to SGTF infection (aOR 0.91, 95{\%}CI 0.68-1.22). These data suggest that while BA.2 may have a competitive advantage over BA.1 in some settings, the clinical profile of illness remains similar. {\#}{\#}{\#} Competing Interest Statement CC has received grant support from South African Medical Research Council, UK Foreign, Commonwealth and Development Office and Wellcome Trust, US Centers for Disease Control and Prevention and Sanofi Pasteur. NW has received grant support from Sanofi Pasteur and the Bill and Melinda Gates Foundation. AvG has received grant support from US Centers for Disease Control and Prevention, Africa Centres for Disease Control and Prevention, African Society for Laboratory Medicine (ASLM), South African Medical Research Council, WHO AFRO, The Fleming Fund and Wellcome Trust. RW declares personal shareholding in the following companies: Adcock Ingram Holdings Ltd, Dischem Pharmacies Ltd, Discovery Ltd, Netcare Ltd, Aspen Pharmacare Holdings Ltd. All other authors declare no conflict of interest. {\#}{\#}{\#} Funding Statement This study was funded by the South African Medical Research Council with funds received from the National Department of Health. Sequencing activities for NICD are supported by a conditional grant from the South African National Department of Health as part of the emergency COVID-19 response; a cooperative agreement between the National Institute for Communicable Diseases of the National Health Laboratory Service and the United States Centers for Disease Control and Prevention (grant number 5 U01IP001048-05-00); the African Society of Laboratory Medicine (ASLM) and Africa Centers for Disease Control and Prevention through a sub-award from the Bill and Melinda Gates Foundation grant number INV-018978; the UK Foreign, Commonwealth and Development Office and Wellcome (Grant no 221003/Z/20/Z); and the UK Department of Health and Social Care and managed by the Fleming Fund and performed under the auspices of the SEQAFRICA project. This research was also supported by The Coronavirus Aid, Relief, and Economic Security Act (CARES ACT) through the Centers for Disease Control and Prevention (CDC) and the COVID International Task Force (ITF) funds through the CDC under the terms of a subcontract with the African Field Epidemiology Network (AFENET) AF-NICD-001/2021. Screening for SGTF at UCT was supported by the Wellcome Centre for Infectious Diseases Research in Africa (CIDRI-Africa), which is supported by core funding from the Wellcome Trust (203135/Z/16/Z and 222754). {\#}{\#}{\#} Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethical approval was obtained from the Human Research Ethics Committee (Medical) of University of the Witwatersrand for the collection of COVID-19 case and test data as part of essential communicable disease surveillance (M210752), and for the DATCOV surveillance programme (M2010108). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes Data used in this manuscript are available upon reasonable request. Proposals should be directed to cherylc{\{}at{\}}nicd.ac.za.},
author = {Wolter, Nicole and Jassat, Waasila and author Group, DATCOV-Gen and von Gottberg, Anne and Cohen, Cheryl},
doi = {10.1101/2022.02.17.22271030},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Wolter et al. - 2022 - Clinical severity of Omicron sub-lineage BA.2 compared to BA.1 in South Africa.pdf:pdf},
journal = {medRxiv},
keywords = {OA,fund{\_}ack,genomics{\_}fund{\_}ack,original},
mendeley-tags = {OA,fund{\_}ack,genomics{\_}fund{\_}ack,original},
month = {feb},
pages = {2022.02.17.22271030},
publisher = {Cold Spring Harbor Laboratory Press},
title = {{Clinical severity of Omicron sub-lineage BA.2 compared to BA.1 in South Africa}},
url = {https://www.medrxiv.org/content/10.1101/2022.02.17.22271030v1 https://www.medrxiv.org/content/10.1101/2022.02.17.22271030v1.abstract},
year = {2022}
}

Early data indicated that infection with Omicron BA.1 sub-lineage was associated with a lower risk of hospitalisation and severe illness, compared to Delta infection. Recently, the BA.2 sub-lineage has increased in many areas globally. We aimed to assess the severity of BA.2 infections compared to BA.1 in South Africa. We performed data linkages for (i) national COVID-19 case data, (ii) SARS-CoV-2 laboratory test data, and (iii) COVID-19 hospitalisations data, nationally. For cases identified using TaqPath COVID-19 PCR, infections were designated as S-gene target failure (SGTF, proxy for BA.1) or S-gene positive (proxy for BA.2). Disease severity was assessed using multivariable logistic regression models comparing individuals with S-gene positive infection to SGTF-infected individuals diagnosed between 1 December 2021 to 20 January 2022. From week 49 (starting 5 December 2021) through week 4 (ending 29 January 2022), the proportion of S-gene positive infections increased from 3% (931/31,271) to 80% (2,425/3,031). The odds of being admitted to hospital did not differ between individuals with S-gene positive (BA.2 proxy) infection compared to SGTF (BA.1 proxy) infection (adjusted odds ratio (aOR) 0.96, 95% confidence interval (CI) 0.85-1.09). Among hospitalised individuals, after controlling for factors associated with severe disease, the odds of severe disease did not differ for individuals with S-gene positive infection compared to SGTF infection (aOR 0.91, 95%CI 0.68-1.22). These data suggest that while BA.2 may have a competitive advantage over BA.1 in some settings, the clinical profile of illness remains similar. ### Competing Interest Statement CC has received grant support from South African Medical Research Council, UK Foreign, Commonwealth and Development Office and Wellcome Trust, US Centers for Disease Control and Prevention and Sanofi Pasteur. NW has received grant support from Sanofi Pasteur and the Bill and Melinda Gates Foundation. AvG has received grant support from US Centers for Disease Control and Prevention, Africa Centres for Disease Control and Prevention, African Society for Laboratory Medicine (ASLM), South African Medical Research Council, WHO AFRO, The Fleming Fund and Wellcome Trust. RW declares personal shareholding in the following companies: Adcock Ingram Holdings Ltd, Dischem Pharmacies Ltd, Discovery Ltd, Netcare Ltd, Aspen Pharmacare Holdings Ltd. All other authors declare no conflict of interest. ### Funding Statement This study was funded by the South African Medical Research Council with funds received from the National Department of Health. Sequencing activities for NICD are supported by a conditional grant from the South African National Department of Health as part of the emergency COVID-19 response; a cooperative agreement between the National Institute for Communicable Diseases of the National Health Laboratory Service and the United States Centers for Disease Control and Prevention (grant number 5 U01IP001048-05-00); the African Society of Laboratory Medicine (ASLM) and Africa Centers for Disease Control and Prevention through a sub-award from the Bill and Melinda Gates Foundation grant number INV-018978; the UK Foreign, Commonwealth and Development Office and Wellcome (Grant no 221003/Z/20/Z); and the UK Department of Health and Social Care and managed by the Fleming Fund and performed under the auspices of the SEQAFRICA project. This research was also supported by The Coronavirus Aid, Relief, and Economic Security Act (CARES ACT) through the Centers for Disease Control and Prevention (CDC) and the COVID International Task Force (ITF) funds through the CDC under the terms of a subcontract with the African Field Epidemiology Network (AFENET) AF-NICD-001/2021. Screening for SGTF at UCT was supported by the Wellcome Centre for Infectious Diseases Research in Africa (CIDRI-Africa), which is supported by core funding from the Wellcome Trust (203135/Z/16/Z and 222754). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethical approval was obtained from the Human Research Ethics Committee (Medical) of University of the Witwatersrand for the collection of COVID-19 case and test data as part of essential communicable disease surveillance (M210752), and for the DATCOV surveillance programme (M2010108). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes Data used in this manuscript are available upon reasonable request. Proposals should be directed to cherylc\at\nicd.ac.za.

@article{Davies2022,
abstract = {Objectives: We aimed to compare COVID-19 outcomes in the Omicron-driven fourth wave with prior waves in the Western Cape, the contribution of undiagnosed prior infection to differences in outcomes in a context of high seroprevalence due to prior infection, and whether protection against severe disease conferred by prior infection and/or vaccination was maintained. Methods: In this cohort study, we included public sector patients aged ≥20 years with a laboratory confirmed COVID-19 diagnosis between 14 November-11 December 2021 (wave four) and equivalent prior wave periods. We compared the risk between waves of the following outcomes using Cox regression: death, severe hospitalization or death and any hospitalization or death (all ≤14 days after diagnosis) adjusted for age, sex, comorbidities, geography, vaccination and prior infection. Results: We included 5,144 patients from wave four and 11,609 from prior waves. Risk of all outcomes was lower in wave four compared to the Delta-driven wave three (adjusted Hazard Ratio (aHR) [95{\%} confidence interval (CI)] for death 0.27 [0.19; 0.38]. Risk reduction was lower when adjusting for vaccination and prior diagnosed infection (aHR:0.41, 95{\%} CI: 0.29; 0.59) and reduced further when accounting for unascertained prior infections (aHR: 0.72). Vaccine protection was maintained in wave four (aHR for outcome of death: 0.24; 95{\%} CI: 0.10; 0.58). Conclusions: In the Omicron-driven wave, severe COVID-19 outcomes were reduced mostly due to protection conferred by prior infection and/or vaccination, but intrinsically reduced virulence may account for an approximately 25{\%} reduced risk of severe hospitalization or death compared to Delta. {\#}{\#}{\#} Competing Interest Statement The authors have declared no competing interest. {\#}{\#}{\#} Funding Statement We acknowledge funding for the Western Cape Provincial Health Data Centre from the Western Cape Department of Health, the US National Institutes for Health (R01 HD080465, U01 AI069924), the Bill and Melinda Gates Foundation (1164272, 119327), the United States Agency for International Development (72067418CA00023), the European Union (101045989), the Wellcome Trust (203135/Z/16/Z, 222574) and the Medical Research Council of South Africa. RJW receives support from the Francis Crick Institute which is funded by Wellcome (FC0010218), MRC (UK) (FC0010218) and Cancer Research UK (FC0010218). He also receives support from Wellcome (203135, 222574) and the Medical Research Council of South Africa. {\#}{\#}{\#} Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Human Research Ethics Committee, University of Cape Town Faculty of Health Sciences, South Africa I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors.},
author = {Davies, Mary-Ann and Kassanjee, Reshma and Rousseau, Petro and Morden, Erna and Johnson, Leigh and Solomon, Wesley and Hsiao, Nei-Yuan and Hussey, Hannah and Meintjes, Graeme A and Paleker, Masudah and Jacobs, Theuns and Raubenheimer, Peter and Heekes, Alexa and Dane, Pierre and Bam, Jamy-Lee and Smith, Mariette and Preiser, Wolfgang and Pienaar, David and Mendelson, Marc and Naude, Jonathan and Schreuder, Neshaad and Mnguni, Ayanda and Roux, Susan Le and Murie, Katie and Prozesky, Hans and Mahomed, Hassan and Rossouw, Liezel and Wasserman, Sean and Maughan, Deborah and Boloko, Linda and Smith, Barry and Taljaard, Jantjie and Symons, Greg and Ntusi, Ntobeko A B and Parker, Arifa and Wolter, Nicole and Jassat, Waasila and Cohen, Cheryl and Lessells, Richard and Wilkinson, Robert J and Arendse, Juanita and Kariem, Saadiq and Moodley, Melvin and Vallabhjee, Krish and Wolmarans, Milani and Boulle, Andrew},
doi = {10.1101/2022.01.12.22269148},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Davies et al. - 2022 - Outcomes of laboratory-confirmed SARS-CoV-2 infection in the Omicron-driven fourth wave compared with previous wa.pdf:pdf},
journal = {medRxiv},
keywords = {OA,fund{\_}ack,genomics{\_}fund{\_}ack,original},
mendeley-tags = {OA,fund{\_}ack,genomics{\_}fund{\_}ack,original},
month = {jan},
pages = {2022.01.12.22269148},
pmid = {35043121},
publisher = {Cold Spring Harbor Laboratory Press},
title = {{Outcomes of laboratory-confirmed SARS-CoV-2 infection in the Omicron-driven fourth wave compared with previous waves in the Western Cape Province, South Africa}},
url = {https://www.medrxiv.org/content/10.1101/2022.01.12.22269148v1 https://www.medrxiv.org/content/10.1101/2022.01.12.22269148v1.abstract},
volume = {13},
year = {2022}
}

Objectives: We aimed to compare COVID-19 outcomes in the Omicron-driven fourth wave with prior waves in the Western Cape, the contribution of undiagnosed prior infection to differences in outcomes in a context of high seroprevalence due to prior infection, and whether protection against severe disease conferred by prior infection and/or vaccination was maintained. Methods: In this cohort study, we included public sector patients aged ≥20 years with a laboratory confirmed COVID-19 diagnosis between 14 November-11 December 2021 (wave four) and equivalent prior wave periods. We compared the risk between waves of the following outcomes using Cox regression: death, severe hospitalization or death and any hospitalization or death (all ≤14 days after diagnosis) adjusted for age, sex, comorbidities, geography, vaccination and prior infection. Results: We included 5,144 patients from wave four and 11,609 from prior waves. Risk of all outcomes was lower in wave four compared to the Delta-driven wave three (adjusted Hazard Ratio (aHR) [95% confidence interval (CI)] for death 0.27 [0.19; 0.38]. Risk reduction was lower when adjusting for vaccination and prior diagnosed infection (aHR:0.41, 95% CI: 0.29; 0.59) and reduced further when accounting for unascertained prior infections (aHR: 0.72). Vaccine protection was maintained in wave four (aHR for outcome of death: 0.24; 95% CI: 0.10; 0.58). Conclusions: In the Omicron-driven wave, severe COVID-19 outcomes were reduced mostly due to protection conferred by prior infection and/or vaccination, but intrinsically reduced virulence may account for an approximately 25% reduced risk of severe hospitalization or death compared to Delta. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement We acknowledge funding for the Western Cape Provincial Health Data Centre from the Western Cape Department of Health, the US National Institutes for Health (R01 HD080465, U01 AI069924), the Bill and Melinda Gates Foundation (1164272, 119327), the United States Agency for International Development (72067418CA00023), the European Union (101045989), the Wellcome Trust (203135/Z/16/Z, 222574) and the Medical Research Council of South Africa. RJW receives support from the Francis Crick Institute which is funded by Wellcome (FC0010218), MRC (UK) (FC0010218) and Cancer Research UK (FC0010218). He also receives support from Wellcome (203135, 222574) and the Medical Research Council of South Africa. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Human Research Ethics Committee, University of Cape Town Faculty of Health Sciences, South Africa I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors.

@article{Hussey2022c,
abstract = {Abstract Background In low- and middle-income countries where SARS-CoV-2 testing is limited, seroprevalence studies can characterise the scale and determinants of the pandemic, as well as elucidate protection conferred by prior exposure. Methods We conducted repeated cross-sectional serosurveys (July 2020 - November 2021) using residual plasma from routine convenient blood samples from patients with non-COVID-19 conditions from Cape Town, South Africa. SARS-CoV-2 anti-nucleocapsid antibodies and linked clinical information were used to investigate: (1) seroprevalence over time and risk factors associated with seropositivity, (2) ecological comparison of seroprevalence between subdistricts, (3) case ascertainment rates, and (4) the relative protection against COVID-19 associated with seropositivity and vaccination statuses, to estimate variant disease severity. Findings Among the subset sampled, seroprevalence of SARS-CoV-2 in Cape Town increased from 39.2{\%} in July 2020 to 67.8{\%} in November 2021. Poorer communities had both higher seroprevalence and COVID-19 mortality. Only 10{\%} of seropositive individuals had a recorded positive SARS-CoV-2 test. Antibody positivity before the start of the Omicron BA.1 wave (28 November 2021) was strongly protective for severe disease (adjusted odds ratio [aOR] 0.15; 95{\%}CI 0.05-0.46), with additional benefit in those who were also vaccinated (aOR 0.07, 95{\%}CI 0.01-0.35). Interpretation The high population seroprevalence in Cape Town was attained at the cost of substantial COVID-19 mortality. At the individual level, seropositivity was highly protective against subsequent infections and severe COVID-19. {\#}{\#}{\#} Competing Interest Statement The authors have declared no competing interest. {\#}{\#}{\#} Funding Statement The study is funded by National Health Laboratory service, Western Cape Department of Health, Wellcome Trust, and in part by the Division of Intramural Research, NIAID, NIH. RJW is supported by the Francis Crick Institute which receives funding from Cancer Research UK (FC0010218), Medical Research Council (FC0010218), and Wellcome (FC0010218). He also received funding from Wellcome (203135,222754). {\#}{\#}{\#} Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study was approved by the University of Cape Town Human Research Ethics Committee (HREC REF 449/2020) and Stellenbosch University Human Research Ethics Committee (N20/08/051). Institutional approval was obtained from the National Health Laboratory Service and the Western Cape Department of Health. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors. The Western Cape Department of Health and Wellness evaluates research proposals for all research in the public health sector in the province, subject to standard research ethics, government approval and data governance prescripts. This includes those that draw on routine datasets like the current study.For more information email Health.Research@westerncape.gov.za},
author = {Hussey, Hannah and Vreede, Helena and Davies, Mary-Ann and Heekes, Alexa and Kalk, Emma and Hardie, Diana Ruth and Zyl, Gert Van and Naidoo, Michelle and Morden, Erna and Bam, Jamy-Lee and Zinyakatira, Nesbert and Centner, Chad and Maritz, Jean and Opie, Jessica and Chapanduka, Zivanai and Mahomed, Hassan and Smith, Mariette and Cois, Annibale and Pienaar, David and Redd, Andrew and Preiser, Wolfgang and Wilkinson, Robert J and Chetty, Kamy and Boulle, Andrew and Hsiao, Nei-yuan Marvin},
doi = {10.1101/2022.12.01.22282927},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Hussey et al. - 2022 - Epidemiology and outcomes of SARS-CoV-2 infection associated with anti-nucleocapsid seropositivity in Cape Town,.pdf:pdf},
journal = {medRxiv},
keywords = {OA,fund{\_}ack,genomics{\_}fund{\_}ack,original},
mendeley-tags = {OA,fund{\_}ack,genomics{\_}fund{\_}ack,original},
month = {dec},
pages = {2022.12.01.22282927},
publisher = {Cold Spring Harbor Laboratory Press},
title = {{Epidemiology and outcomes of SARS-CoV-2 infection associated with anti-nucleocapsid seropositivity in Cape Town, South Africa}},
url = {https://www.medrxiv.org/content/10.1101/2022.12.01.22282927v1 https://www.medrxiv.org/content/10.1101/2022.12.01.22282927v1.abstract},
year = {2022}
}

Abstract Background In low- and middle-income countries where SARS-CoV-2 testing is limited, seroprevalence studies can characterise the scale and determinants of the pandemic, as well as elucidate protection conferred by prior exposure. Methods We conducted repeated cross-sectional serosurveys (July 2020 - November 2021) using residual plasma from routine convenient blood samples from patients with non-COVID-19 conditions from Cape Town, South Africa. SARS-CoV-2 anti-nucleocapsid antibodies and linked clinical information were used to investigate: (1) seroprevalence over time and risk factors associated with seropositivity, (2) ecological comparison of seroprevalence between subdistricts, (3) case ascertainment rates, and (4) the relative protection against COVID-19 associated with seropositivity and vaccination statuses, to estimate variant disease severity. Findings Among the subset sampled, seroprevalence of SARS-CoV-2 in Cape Town increased from 39.2% in July 2020 to 67.8% in November 2021. Poorer communities had both higher seroprevalence and COVID-19 mortality. Only 10% of seropositive individuals had a recorded positive SARS-CoV-2 test. Antibody positivity before the start of the Omicron BA.1 wave (28 November 2021) was strongly protective for severe disease (adjusted odds ratio [aOR] 0.15; 95%CI 0.05-0.46), with additional benefit in those who were also vaccinated (aOR 0.07, 95%CI 0.01-0.35). Interpretation The high population seroprevalence in Cape Town was attained at the cost of substantial COVID-19 mortality. At the individual level, seropositivity was highly protective against subsequent infections and severe COVID-19. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement The study is funded by National Health Laboratory service, Western Cape Department of Health, Wellcome Trust, and in part by the Division of Intramural Research, NIAID, NIH. RJW is supported by the Francis Crick Institute which receives funding from Cancer Research UK (FC0010218), Medical Research Council (FC0010218), and Wellcome (FC0010218). He also received funding from Wellcome (203135,222754). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study was approved by the University of Cape Town Human Research Ethics Committee (HREC REF 449/2020) and Stellenbosch University Human Research Ethics Committee (N20/08/051). Institutional approval was obtained from the National Health Laboratory Service and the Western Cape Department of Health. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors. The Western Cape Department of Health and Wellness evaluates research proposals for all research in the public health sector in the province, subject to standard research ethics, government approval and data governance prescripts. This includes those that draw on routine datasets like the current study.For more information email Health.Research@westerncape.gov.za

@article{VandenBerg2022,
abstract = {There is a need for effective therapy for COVID-19 pneumonia. Convalescent plasma has antiviral activity and early observational studies suggested benefit in reducing COVID-19 severity. We investigated the safety and efficacy of convalescent plasma in hospitalized patients with COVID-19 in a population with a high HIV prevalence and where few therapeutic options were available. We performed a double-blinded, multicenter, randomized controlled trial in one private and three public sector hospitals in South Africa. Adult participants with COVID-19 pneumonia requiring non-invasive oxygen were randomized 1:1 to receive a single transfusion of 200 mL of either convalescent plasma or 0.9{\%} saline solution. The primary outcome measure was hospital discharge and/or improvement of ≥ 2 points on the World Health Organisation Blueprint Ordinal Scale for Clinical Improvement by day 28 of enrolment. The trial was stopped early for futility by the Data and Safety Monitoring Board. 103 participants, including 21 HIV positive individuals, were randomized at the time of premature trial termination: 52 in the convalescent plasma and 51 in the placebo group. The primary outcome occurred in 31 participants in the convalescent plasma group and and 32 participants in the placebo group (relative risk 1.03 (95{\%} CI 0.77 to 1.38). Two grade 1 transfusion-related adverse events occurred. Participants who improved clinically received convalescent plasma with a higher median anti-SARS-CoV-2 neutralizing antibody titre compared with those who did not (298 versus 205 AU/mL). Our study contributes additional evidence for recommendations against the use of convalescent plasma for COVID-19 pneumonia. Safety and feasibility in this population supports future investigation for other indications.},
author = {van den Berg, Karin and Glatt, Tanya Nadia and Vermeulen, Marion and Little, Francesca and Swanevelder, Ronel and Barrett, Claire and Court, Richard and Bremer, Marise and Nyoni, Cynthia and Swarts, Avril and Mmenu, Cordelia and Crede, Thomas and Kritzinger, Gerdien and Naude, Jonathan and Szymanski, Patryk and Cowley, James and Moyo-Gwete, Thandeka and Moore, Penny L and Black, John and Singh, Jaimendra and Bhiman, Jinal N and Baijnath, Prinita and Mody, Priyesh and Malherbe, Jacques and Potgieter, Samantha and van Vuuren, Cloete and Maasdorp, Shaun and Wilkinson, Robert J and Louw, Vernon J and Wasserman, Sean},
doi = {10.1038/s41598-022-06221-8},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/van den Berg et al. - 2022 - Convalescent plasma in the treatment of moderate to severe COVID-19 pneumonia a randomized controlled trial.pdf:pdf},
isbn = {0123456789},
issn = {2045-2322},
journal = {Scientific Reports},
keywords = {Clinical trial design,Clinical trials,OA,OA{\_}PMC,Randomized controlled trials,fund{\_}ack,genomics{\_}fund{\_}ack,original},
mendeley-tags = {OA,OA{\_}PMC,fund{\_}ack,genomics{\_}fund{\_}ack,original},
month = {dec},
number = {1},
pages = {2552},
pmid = {35169169},
publisher = {Nature Publishing Group},
title = {{Convalescent plasma in the treatment of moderate to severe COVID-19 pneumonia: a randomized controlled trial (PROTECT-Patient Trial)}},
url = {https://www.nature.com/articles/s41598-022-06221-8},
volume = {12},
year = {2022}
}

There is a need for effective therapy for COVID-19 pneumonia. Convalescent plasma has antiviral activity and early observational studies suggested benefit in reducing COVID-19 severity. We investigated the safety and efficacy of convalescent plasma in hospitalized patients with COVID-19 in a population with a high HIV prevalence and where few therapeutic options were available. We performed a double-blinded, multicenter, randomized controlled trial in one private and three public sector hospitals in South Africa. Adult participants with COVID-19 pneumonia requiring non-invasive oxygen were randomized 1:1 to receive a single transfusion of 200 mL of either convalescent plasma or 0.9% saline solution. The primary outcome measure was hospital discharge and/or improvement of ≥ 2 points on the World Health Organisation Blueprint Ordinal Scale for Clinical Improvement by day 28 of enrolment. The trial was stopped early for futility by the Data and Safety Monitoring Board. 103 participants, including 21 HIV positive individuals, were randomized at the time of premature trial termination: 52 in the convalescent plasma and 51 in the placebo group. The primary outcome occurred in 31 participants in the convalescent plasma group and and 32 participants in the placebo group (relative risk 1.03 (95% CI 0.77 to 1.38). Two grade 1 transfusion-related adverse events occurred. Participants who improved clinically received convalescent plasma with a higher median anti-SARS-CoV-2 neutralizing antibody titre compared with those who did not (298 versus 205 AU/mL). Our study contributes additional evidence for recommendations against the use of convalescent plasma for COVID-19 pneumonia. Safety and feasibility in this population supports future investigation for other indications.

@article{Wolter2022d,
abstract = {Omicron lineages BA.4 and BA.5 drove a fifth wave of COVID-19 cases in South Africa. Here, we use the presence/absence of the S-gene target as a proxy for SARS-CoV-2 variant/lineage for infections diagnosed using the TaqPath PCR assay between 1 October 2021 and 26 April 2022. We link national COVID-19 individual-level data including case, laboratory test and hospitalisation data. We assess severity using multivariable logistic regression comparing the risk of hospitalisation and risk of severe disease, once hospitalised, for Delta, BA.1, BA.2 and BA.4/BA.5 infections. After controlling for factors associated with hospitalisation and severe outcome respectively, BA.4/BA.5-infected individuals had a similar odds of hospitalisation (aOR 1.24, 95{\%} CI 0.98–1.55) and severe outcome (aOR 0.72, 95{\%} CI 0.41–1.26) compared to BA.1-infected individuals. Newly emerged Omicron lineages BA.4/BA.5 showed similar severity to the BA.1 lineage and continued to show reduced clinical severity compared to the Delta variant. South Africa experienced a resurgence in COVID-19 in 2022 driven by Omicron subvariants BA.4 and BA.5. Here, the authors investigate the severity of infections caused by these subvariants, and find no difference in the risk of severe outcomes when compared to Omicron BA.1, whilst all Omicron subvariants were less severe than Delta.},
author = {Wolter, Nicole and Jassat, Waasila and Walaza, Sibongile and Welch, Richard and Moultrie, Harry and Groome, Michelle J. and Amoako, Daniel Gyamfi and Everatt, Josie and Bhiman, Jinal N. and Scheepers, Cathrine and Tebeila, Naume and Chiwandire, Nicola and du Plessis, Mignon and Govender, Nevashan and Ismail, Arshad and Glass, Allison and Mlisana, Koleka and Stevens, Wendy and Treurnicht, Florette K. and Subramoney, Kathleen and Makatini, Zinhle and Hsiao, Nei-yuan and Parboosing, Raveen and Wadula, Jeannette and Hussey, Hannah and Davies, Mary-Ann and Boulle, Andrew and von Gottberg, Anne and Cohen, Cheryl},
doi = {10.1038/s41467-022-33614-0},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Wolter et al. - 2022 - Clinical severity of SARS-CoV-2 Omicron BA.4 and BA.5 lineages compared to BA.1 and Delta in South Africa.pdf:pdf},
issn = {2041-1723},
journal = {Nature Communications},
keywords = {2,CoV,Epidemiology,OA,Risk factors,SARS,Viral infection,fund{\_}ack,genomics{\_}fund{\_}ack,original},
mendeley-tags = {OA,fund{\_}ack,genomics{\_}fund{\_}ack,original},
month = {oct},
pages = {5860},
pmid = {36195617},
publisher = {Nature Publishing Group},
title = {{Clinical severity of SARS-CoV-2 Omicron BA.4 and BA.5 lineages compared to BA.1 and Delta in South Africa}},
url = {https://www.nature.com/articles/s41467-022-33614-0},
volume = {13},
year = {2022}
}

Omicron lineages BA.4 and BA.5 drove a fifth wave of COVID-19 cases in South Africa. Here, we use the presence/absence of the S-gene target as a proxy for SARS-CoV-2 variant/lineage for infections diagnosed using the TaqPath PCR assay between 1 October 2021 and 26 April 2022. We link national COVID-19 individual-level data including case, laboratory test and hospitalisation data. We assess severity using multivariable logistic regression comparing the risk of hospitalisation and risk of severe disease, once hospitalised, for Delta, BA.1, BA.2 and BA.4/BA.5 infections. After controlling for factors associated with hospitalisation and severe outcome respectively, BA.4/BA.5-infected individuals had a similar odds of hospitalisation (aOR 1.24, 95% CI 0.98–1.55) and severe outcome (aOR 0.72, 95% CI 0.41–1.26) compared to BA.1-infected individuals. Newly emerged Omicron lineages BA.4/BA.5 showed similar severity to the BA.1 lineage and continued to show reduced clinical severity compared to the Delta variant. South Africa experienced a resurgence in COVID-19 in 2022 driven by Omicron subvariants BA.4 and BA.5. Here, the authors investigate the severity of infections caused by these subvariants, and find no difference in the risk of severe outcomes when compared to Omicron BA.1, whilst all Omicron subvariants were less severe than Delta.

@article{Davies2022a,
abstract = {Objective: We aimed to compare clinical severity of Omicron BA.4/BA.5 infection with BA.1 and earlier variant infections among laboratory-confirmed SARS-CoV-2 cases in the Western Cape, South Africa, using timing of infection to infer the lineage/variant causing infection. Methods: We included public sector patients aged ≥20 years with laboratory-confirmed COVID-19 between 1-21 May 2022 (BA.4/BA.5 wave) and equivalent prior wave periods. We compared the risk between waves of (i) death and (ii) severe hospitalization/death (all within 21 days of diagnosis) using Cox regression adjusted for demographics, comorbidities, admission pressure, vaccination and prior infection. Results: Among 3,793 patients from the BA.4/BA.5 wave and 190,836 patients from previous waves the risk of severe hospitalization/death was similar in the BA.4/BA.5 and BA.1 waves (adjusted hazard ratio (aHR) 1.01; 95{\%} confidence interval (CI) 0.92; 1.12). Both Omicron waves had lower risk of severe outcomes than previous waves. Prior infection (aHR 0.19, 95{\%} CI 0.16; 0.22) and vaccination (aHR 0.24; 95{\%} CI 0.15; 0.39 for boosted vs. no vaccine) were protective. Conclusion: Disease severity was similar amongst diagnosed COVID-19 cases in the BA.4/BA.5 and BA.1 periods in the context of growing immunity against SARS-CoV-2 due to prior infection and vaccination, both of which were strongly protective. {\#}{\#}{\#} Competing Interest Statement The authors have declared no competing interest. {\#}{\#}{\#} Funding Statement We acknowledge funding for the Western Cape Provincial Health Data Centre from the Western Cape Department of Health, the US National Institutes for Health (R01 HD080465, U01 AI069924), the Bill and Melinda Gates Foundation (1164272, 1191327), the United States Agency for International Development (72067418CA00023), the European Union (101045989) and the Grand Challenges ICODA pilot initiative delivered by Health Data Research UK and funded by the Bill {\&} Melinda Gates and Minderoo Foundations (INV-017293). Funding was also received from Wellcome (203135/Z/16/Z [RJW, GM, WCPHDC], 222574 [RJW, WCPHDC] 214321/Z/18/Z [GM]) and the Medical Research Council of South Africa (RJW, MAD). RJW additionally receives support from the Francis Crick Institute which is funded by Wellcome (FC0010218), MRC (UK) (FC0010218), and Cancer Research UK (FC0010218). GM is also funded by the South African Research Chairs Initiative of the Department of Science and Technology and National Research Foundation (NRF) of South Africa (Grant No 64787). The funders had no role in the study design, data collection, data analysis, data interpretation, or writing of this report. The opinions, findings and conclusions expressed in this manuscript reflect those of the authors alone. {\#}{\#}{\#} Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study was approved by the University of Cape Town and Stellenbosch University Health Research Ethics Committees and Western Cape Government: Health. Individual informed consent requirement was waived for this secondary analysis of de-identified data. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes The underlying data are de-identified pseudo-anonymised routine patient records for which patients have not consented to their de-identified data being part of publicly accessible repositories with inherent risks of re-identification. The Western Cape Department of Health and Wellness evaluates research proposals for all research in the public health sector in the Province, including those which draw on similar datasets to the current study, based on routine data, subject to standard research ethics, government approval and data governance prescripts.},
author = {Davies, Mary-Ann and Morden, Erna and Rosseau, Petro and Arendse, Juanita and Bam, Jamy-Lee and Boloko, Linda and Cloete, Keith and Cohen, Cheryl and Chetty, Nicole and Dane, Pierre and Heekes, Alexa and Hsiao, Nei-Yuan and Hunter, Mehreen and Hussey, Hannah and Jacobs, Theuns and Jassat, Waasila and Kariem, Saadiq and Kassanjee, Reshma and Laenen, Inneke and Roux, Sue Le and Lessells, Richard and Mahomed, Hassan and Maughan, Deborah and Meintjes, Graeme A and Mendelson, Marc and Mnguni, Ayanda and Moodley, Melvin and Murie, Katy and Naude, Jonathan and Ntusi, Ntobeko A B and Paleker, Masudah and Parker, Arifa and Pienaar, David and Preiser, Wolfgang and Prozesky, Hans and Raubenheimer, Peter and Rossouw, Liezel and Schreuder, Neshaad and Smith, Barry and Smith, Mariette and Solomon, Wesley and Symons, Greg and Taljaard, Jantjie and Wasserman, Sean and Wilkinson, Robert J and Wolmarans, Milani and Wolter, Nicole and Boulle, Andrew and and Wellness, Western Cape Department of Health and of Health, National Departments and {National Institute for Communicable Diseases in South Africa}},
doi = {10.1101/2022.06.28.22276983},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Davies et al. - 2022 - Outcomes of laboratory-confirmed SARS-CoV-2 infection during resurgence driven by Omicron lineages BA.4 and BA.5.pdf:pdf},
journal = {medRxiv},
keywords = {OA,fund{\_}ack,genomics{\_}fund{\_}ack,original},
mendeley-tags = {OA,fund{\_}ack,genomics{\_}fund{\_}ack,original},
month = {jun},
number = {5},
pages = {2022.06.28.22276983},
publisher = {Cold Spring Harbor Laboratory Press},
title = {{Outcomes of laboratory-confirmed SARS-CoV-2 infection during resurgence driven by Omicron lineages BA.4 and BA.5 compared with previous waves in the Western Cape Province, South Africa}},
url = {https://www.medrxiv.org/content/10.1101/2022.06.28.22276983v1 https://www.medrxiv.org/content/10.1101/2022.06.28.22276983v1.abstract},
volume = {13},
year = {2022}
}

Objective: We aimed to compare clinical severity of Omicron BA.4/BA.5 infection with BA.1 and earlier variant infections among laboratory-confirmed SARS-CoV-2 cases in the Western Cape, South Africa, using timing of infection to infer the lineage/variant causing infection. Methods: We included public sector patients aged ≥20 years with laboratory-confirmed COVID-19 between 1-21 May 2022 (BA.4/BA.5 wave) and equivalent prior wave periods. We compared the risk between waves of (i) death and (ii) severe hospitalization/death (all within 21 days of diagnosis) using Cox regression adjusted for demographics, comorbidities, admission pressure, vaccination and prior infection. Results: Among 3,793 patients from the BA.4/BA.5 wave and 190,836 patients from previous waves the risk of severe hospitalization/death was similar in the BA.4/BA.5 and BA.1 waves (adjusted hazard ratio (aHR) 1.01; 95% confidence interval (CI) 0.92; 1.12). Both Omicron waves had lower risk of severe outcomes than previous waves. Prior infection (aHR 0.19, 95% CI 0.16; 0.22) and vaccination (aHR 0.24; 95% CI 0.15; 0.39 for boosted vs. no vaccine) were protective. Conclusion: Disease severity was similar amongst diagnosed COVID-19 cases in the BA.4/BA.5 and BA.1 periods in the context of growing immunity against SARS-CoV-2 due to prior infection and vaccination, both of which were strongly protective. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement We acknowledge funding for the Western Cape Provincial Health Data Centre from the Western Cape Department of Health, the US National Institutes for Health (R01 HD080465, U01 AI069924), the Bill and Melinda Gates Foundation (1164272, 1191327), the United States Agency for International Development (72067418CA00023), the European Union (101045989) and the Grand Challenges ICODA pilot initiative delivered by Health Data Research UK and funded by the Bill & Melinda Gates and Minderoo Foundations (INV-017293). Funding was also received from Wellcome (203135/Z/16/Z [RJW, GM, WCPHDC], 222574 [RJW, WCPHDC] 214321/Z/18/Z [GM]) and the Medical Research Council of South Africa (RJW, MAD). RJW additionally receives support from the Francis Crick Institute which is funded by Wellcome (FC0010218), MRC (UK) (FC0010218), and Cancer Research UK (FC0010218). GM is also funded by the South African Research Chairs Initiative of the Department of Science and Technology and National Research Foundation (NRF) of South Africa (Grant No 64787). The funders had no role in the study design, data collection, data analysis, data interpretation, or writing of this report. The opinions, findings and conclusions expressed in this manuscript reflect those of the authors alone. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study was approved by the University of Cape Town and Stellenbosch University Health Research Ethics Committees and Western Cape Government: Health. Individual informed consent requirement was waived for this secondary analysis of de-identified data. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes The underlying data are de-identified pseudo-anonymised routine patient records for which patients have not consented to their de-identified data being part of publicly accessible repositories with inherent risks of re-identification. The Western Cape Department of Health and Wellness evaluates research proposals for all research in the public health sector in the Province, including those which draw on similar datasets to the current study, based on routine data, subject to standard research ethics, government approval and data governance prescripts.

@article{Tegally2022b,
abstract = {Three lineages (BA.1, BA.2 and BA.3) of the SARS-CoV-2 Omicron variant of concern predominantly drove South Africa's fourth COVID-19 wave. We have now identified two new lineages, BA.4 and BA.5, responsible for a fifth wave of infections. The spike proteins of BA.4 and BA.5 are identical, and comparable to BA.2 except for the addition of 69-70del (present in the Alpha variant and the BA.1 lineage), L452R (present in the Delta variant), F486V and the wild type amino acid at Q493.The two lineages only differ outside of the spike region. The 69-70 deletion in spike allows these lineages to be identified by the proxy marker of S-gene target failure, on the background of variants not possessing this feature . BA.4 and BA.5 have rapidly replaced BA.2, reaching more than 50{\%} of sequenced cases in South Africa by the first week of April 2022. Using a multinomial logistic regression model, we estimate growth advantages for BA.4 and BA.5 of 0.08 (95{\%} CI: 0.08 - 0.09) and 0.10 (95{\%} CI: 0.09 - 0.11) per day respectively over BA.2 in South Africa. The continued discovery of genetically diverse Omicron lineages points to the hypothesis that a discrete reservoir, such as human chronic infections and/or animal hosts, is potentially contributing to further evolution and dispersal of the virus.},
author = {Tegally, Houriiyah and Moir, Monika and Everatt, Josie and Giovanetti, Marta and Scheepers, Cathrine and Wilkinson, Eduan and Subramoney, Kathleen and Makatini, Zinhle and Moyo, Sikhulile and Amoako, Daniel G and Baxter, Cheryl and Althaus, Christian L and Anyaneji, Ugochukwu J and Kekana, Dikeledi and Viana, Raquel and Giandhari, Jennifer and Lessells, Richard J and Maponga, Tongai and Maruapula, Dorcas and Choga, Wonderful and Matshaba, Mogomotsi and Mbulawa, Mpaphi B and Msomi, Nokukhanya and NGS-SA consortium and Naidoo, Yeshnee and Pillay, Sureshnee and Sanko, Tomasz Janusz and San, James E and Scott, Lesley and Singh, Lavanya and Magini, Nonkululeko A and Smith-Lawrence, Pamela and Stevens, Wendy and Dor, Graeme and Tshiabuila, Derek and Wolter, Nicole and Preiser, Wolfgang and Treurnicht, Florette K and Venter, Marietjie and Chiloane, Georginah and McIntyre, Caitlyn and O'Toole, Aine and Ruis, Christopher and Peacock, Thomas P and Roemer, Cornelius and Pond, Sergei L Kosakovsky and Williamson, Carolyn and Pybus, Oliver G and Bhiman, Jinal N and Glass, Allison and Martin, Darren P and Jackson, Ben and Rambaut, Andrew and Laguda-Akingba, Oluwakemi and Gaseitsiwe, Simani and von Gottberg, Anne and de Oliveira, Tulio},
doi = {10.1038/s41591-022-01911-2},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Tegally et al. - 2022 - Emergence of SARS-CoV-2 Omicron lineages BA.4 and BA.5 in South Africa.pdf:pdf},
issn = {1546-170X},
journal = {Nature Medicine},
keywords = {Epidemiology,OA,Phylogeny,fund{\_}not{\_}ack,original},
mendeley-tags = {OA,fund{\_}not{\_}ack,original},
month = {jun},
number = {9},
pages = {1785--1790},
pmid = {35760080},
publisher = {Nature Publishing Group},
title = {{Emergence of SARS-CoV-2 Omicron lineages BA.4 and BA.5 in South Africa}},
url = {https://www.nature.com/articles/s41591-022-01911-2},
volume = {28},
year = {2022}
}

Three lineages (BA.1, BA.2 and BA.3) of the SARS-CoV-2 Omicron variant of concern predominantly drove South Africa's fourth COVID-19 wave. We have now identified two new lineages, BA.4 and BA.5, responsible for a fifth wave of infections. The spike proteins of BA.4 and BA.5 are identical, and comparable to BA.2 except for the addition of 69-70del (present in the Alpha variant and the BA.1 lineage), L452R (present in the Delta variant), F486V and the wild type amino acid at Q493.The two lineages only differ outside of the spike region. The 69-70 deletion in spike allows these lineages to be identified by the proxy marker of S-gene target failure, on the background of variants not possessing this feature . BA.4 and BA.5 have rapidly replaced BA.2, reaching more than 50% of sequenced cases in South Africa by the first week of April 2022. Using a multinomial logistic regression model, we estimate growth advantages for BA.4 and BA.5 of 0.08 (95% CI: 0.08 - 0.09) and 0.10 (95% CI: 0.09 - 0.11) per day respectively over BA.2 in South Africa. The continued discovery of genetically diverse Omicron lineages points to the hypothesis that a discrete reservoir, such as human chronic infections and/or animal hosts, is potentially contributing to further evolution and dispersal of the virus.

@article{Mullins2022,
author = {Mullins, Michelle O and Smith, Muneerah and Maboreke, Hazel and Nel, Andrew J M and Ntusi, Ntobeko A B and Burgers, Wendy A and Blackburn, Jonathan M},
doi = {10.20944/PREPRINTS202212.0518.V1},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Mullins et al. - 2022 - Epitope coverage of anti-SARS-CoV-2 nucleocapsid IgA and IgG antibodies correlates with protection against re-in.pdf:pdf},
journal = {Preprints},
keywords = {OA,SARS-CoV-2 antibodies,SARS-CoV-2 re-infection,epitope coverage,fund{\_}not{\_}ack,humoral response,immunoassay,original,protein microarray,quantitative antibody binding},
mendeley-tags = {OA,fund{\_}not{\_}ack,original},
month = {dec},
pages = {2022120518},
publisher = {Preprints},
title = {{Epitope coverage of anti-SARS-CoV-2 nucleocapsid IgA and IgG antibodies correlates with protection against re-infection by new variants in subsequent waves of the COVID-19 pandemic}},
url = {https://www.preprints.org/manuscript/202212.0518/v1},
year = {2022}
}

@article{Martin2022a,
author = {Martin, Darren P and Lytras, Spyros and Lucaci, Alexander G and Maier, Wolfgang and Gr{\"{u}}ning, Bj{\"{o}}rn and Shank, Stephen D and Weaver, Steven and MacLean, Oscar A and Orton, Richard J and Lemey, Philippe and Boni, Maciej F and Tegally, Houriiyah and Harkins, Gordon W and Scheepers, Cathrine and Bhiman, Jinal N and Everatt, Josie and Amoako, Daniel G and San, James Emmanuel and Giandhari, Jennifer and Sigal, Alex and NGS-SA and Williamson, Carolyn and Hsiao, Nei-yuan and von Gottberg, Anne and {De Klerk}, Arne and Shafer, Robert W and Robertson, David L and Wilkinson, Robert J and Sewell, B Trevor and Lessells, Richard and Nekrutenko, Anton and Greaney, Allison J and Starr, Tyler N and Bloom, Jesse D and Murrell, Ben and Wilkinson, Eduan and Gupta, Ravindra K and de Oliveira, Tulio and {Kosakovsky Pond}, Sergei L},
doi = {10.1093/MOLBEV/MSAC061},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Martin et al. - 2022 - Selection analysis identifies clusters of unusual mutational changes in Omicron lineage BA.1 that likely impact S.pdf:pdf},
isbn = {061/6553617},
issn = {0737-4038},
journal = {Molecular Biology and Evolution},
keywords = {OA,fund{\_}ack,genomics{\_}fund{\_}ack,original},
mendeley-tags = {OA,fund{\_}ack,genomics{\_}fund{\_}ack,original},
number = {4},
pages = {msac061},
pmid = {35325204},
title = {{Selection analysis identifies clusters of unusual mutational changes in Omicron lineage BA.1 that likely impact Spike function}},
url = {https://academic.oup.com/mbe/advance-article/doi/10.1093/molbev/msac061/6553617},
volume = {39},
year = {2022}
}

@article{Wolter2022c,
abstract = {Omicron lineages BA.4 and BA.5 drove a fifth wave of COVID-19 cases in South Africa. We assessed the severity of BA.4/BA.5 infections using the presence/absence of the S-gene target for infections diagnosed using the TaqPath PCR assay between 1 October 2021 and 26 April 2022. We linked national COVID-19 individual-level data including case, laboratory test and hospitalisation data. We assessed severity using multivariable logistic regression comparing the risk of hospitalisation and risk of severe disease, once hospitalised, for Delta, BA.1, BA.2 and BA.4/BA.5 infections. After controlling for factors associated with hospitalisation and severe outcome respectively, BA.4/BA.5-infected individuals had a similar odds of hospitalisation (aOR1.24, 95{\%} CI 0.98–1.55) and severe outcome (aOR 0.71, 95{\%}CI 0.41–1.25) compared to BA.1-infected individuals. Newly emerged Omicron lineages BA.4/BA.5 continue to show reduced clinical severity compared to previous variants, as observed for Omicron BA.1.},
author = {Wolter, Nicole and Jassat, Waasila and Welch, Richard and Moultrie, Harry and Groome, Michelle and Amoako, Daniel and Everatt, Josie and Bhiman, Jinal and Scheepers, Cathrine and Chiwandire, Nicola},
doi = {10.21203/RS.3.RS-1792132/V1},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Wolter et al. - 2022 - Clinical severity of SARS-CoV-2 Omicron BA.4 and BA.5 lineages in South Africa.pdf:pdf},
journal = {Research Square},
keywords = {OA,fund{\_}ack,genomics{\_}fund{\_}ack,original},
mendeley-tags = {OA,fund{\_}ack,genomics{\_}fund{\_}ack,original},
month = {jun},
pages = {10.21203/rs.3.rs--1792132/v1},
title = {{Clinical severity of SARS-CoV-2 Omicron BA.4 and BA.5 lineages in South Africa}},
url = {https://www.researchsquare.com https://www.researchsquare.com/article/rs-1792132/v1},
year = {2022}
}

Omicron lineages BA.4 and BA.5 drove a fifth wave of COVID-19 cases in South Africa. We assessed the severity of BA.4/BA.5 infections using the presence/absence of the S-gene target for infections diagnosed using the TaqPath PCR assay between 1 October 2021 and 26 April 2022. We linked national COVID-19 individual-level data including case, laboratory test and hospitalisation data. We assessed severity using multivariable logistic regression comparing the risk of hospitalisation and risk of severe disease, once hospitalised, for Delta, BA.1, BA.2 and BA.4/BA.5 infections. After controlling for factors associated with hospitalisation and severe outcome respectively, BA.4/BA.5-infected individuals had a similar odds of hospitalisation (aOR1.24, 95% CI 0.98–1.55) and severe outcome (aOR 0.71, 95%CI 0.41–1.25) compared to BA.1-infected individuals. Newly emerged Omicron lineages BA.4/BA.5 continue to show reduced clinical severity compared to previous variants, as observed for Omicron BA.1.

@article{Martin2021a,
abstract = {Summary The independent emergence late in 2020 of the B.1.1.7, B.1.351, and P.1 lineages of SARS-CoV-2 prompted renewed concerns about the evolutionary capacity of this virus to overcome public health interventions and rising population immunity. Here, by examining patterns of synonymous and non-synonymous mutations that have accumulated in SARS-CoV-2 genomes since the pandemic began, we find that the emergence of these three "501Y lineages" coincided with a major global shift in the selective forces acting on various SARS-CoV-2 genes. Following their emergence, the adaptive evolution of 501Y lineage viruses has involved repeated selectively favored convergent mutations at 35 genome sites, mutations we refer to as the 501Y meta-signature. The ongoing convergence of viruses in many other lineages on this meta-signature suggests that it includes multiple mutation combinations capable of promoting the persistence of diverse SARS-CoV-2 lineages in the face of mounting host immune recognition.},
author = {Martin, Darren P and Weaver, Steven and Tegally, Houriiyah and San, James Emmanuel and Shank, Stephen D and Wilkinson, Eduan and Lucaci, Alexander G and Giandhari, Jennifer and Naidoo, Sureshnee and Pillay, Yeshnee and Singh, Lavanya and Lessells, Richard J and Gupta, Ravindra K and Wertheim, Joel O and Nekturenko, Anton and Murrell, Ben and Harkins, Gordon W and Lemey, Philippe and MacLean, Oscar A and Robertson, David L and de Oliveira, Tulio and Pond, Sergei L Kosakovsky},
doi = {10.1016/J.CELL.2021.09.003},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Martin et al. - 2021 - The emergence and ongoing convergent evolution of the SARS-CoV-2 N501Y lineages.pdf:pdf},
issn = {0092-8674},
journal = {Cell},
keywords = {COVID 19,convergent mutations,directional selection,diversifying selection,evolutionary adaptation,genomics{\_}fund{\_}ack,immune evasion,lineage-defining mutations,original,positive selection,recurrent mutations,transmission advantage},
mendeley-tags = {genomics{\_}fund{\_}ack,original},
month = {sep},
number = {20},
pages = {5189--5200},
pmid = {34537136},
publisher = {Elsevier},
title = {{The emergence and ongoing convergent evolution of the SARS-CoV-2 N501Y lineages}},
url = {http://www.cell.com/article/S0092867421010503/fulltext http://www.cell.com/article/S0092867421010503/abstract https://www.cell.com/cell/abstract/S0092-8674(21)01050-3},
volume = {184},
year = {2021}
}

Summary The independent emergence late in 2020 of the B.1.1.7, B.1.351, and P.1 lineages of SARS-CoV-2 prompted renewed concerns about the evolutionary capacity of this virus to overcome public health interventions and rising population immunity. Here, by examining patterns of synonymous and non-synonymous mutations that have accumulated in SARS-CoV-2 genomes since the pandemic began, we find that the emergence of these three "501Y lineages" coincided with a major global shift in the selective forces acting on various SARS-CoV-2 genes. Following their emergence, the adaptive evolution of 501Y lineage viruses has involved repeated selectively favored convergent mutations at 35 genome sites, mutations we refer to as the 501Y meta-signature. The ongoing convergence of viruses in many other lineages on this meta-signature suggests that it includes multiple mutation combinations capable of promoting the persistence of diverse SARS-CoV-2 lineages in the face of mounting host immune recognition.

@article{Martin2021,
abstract = {The emergence and rapid rise in prevalence of three independent SARS-CoV-2 '501Y lineages', B.1.1.7, B.1.351 and P.1, in the last three months of 2020 has prompted renewed concerns about the evolutionarily capacity of SARS-CoV-2 to adapt to both rising population immunity and public health interventions such as vaccines and social distancing. Viruses giving rise to the different 501Y lineages have, presumably under intense natural selection following a shift in host environment, independently acquired multiple unique and convergent mutations. As a consequence all have gained epidemiological and immunological properties that will likely complicate the control of COVID-19. Here, by examining patterns of mutations that arose in SARS-CoV-2 genomes during the pandemic we find evidence of a major change in the selective forces acting on immunologically important SARS-CoV-2 genes (such as N and S) that likely coincided with the emergence of the 501Y lineages. In addition to involving continuing sequence diversification, we find evidence that a significant portion of the ongoing adaptive evolution of the 501Y lineages also involves further convergence between the lineages. Our findings highlight the importance of monitoring how members of these known 501Y lineages, and others still undiscovered, are convergently evolving similar strategies to ensure their persistence in the face of mounting infection and vaccine induced host immune recognition. {\#}{\#}{\#} Competing Interest Statement JOW has received funding from Gilead Sciences, LLC (completed) and the CDC (ongoing) via grants and contracts to his institution unrelated to this research. {\#}{\#}{\#} Funding Statement DPM is funded by the Wellcome Trust (222574/Z/21/Z) SLKP was supported by the following grants from the U.S. National Institutes of Health R01 AI134384 (NIH/NIAID), R01 AI140970 (NIH/NIAID), and a RAPID award from the US National Science Foundation 2027196 (NSF/DBI,BIO). DLR is funded by the Medical Research Council (MC$\backslash${\_}UU$\backslash${\_}1201412) and Wellcome Trust (220977/Z/20/Z). OAM is funded by the Wellcome Trust (206369/Z/17/Z). COG-UK is supported by funding from the Medical Research Council (MRC) part of UK Research {\&} Innovation (UKRI), the National Institute of Health Research (NIHR) and Genome Research Limited, operating as the Wellcome Sanger Institute. PL acknowledges funding from the European Research Council under the European Union's Horizon 2020 research and innovation programme (grant agreement no. 725422-ReservoirDOCS), the EU grant 874850 MOOD and the Wellcome Trust through project 206298/Z/17/Z. JOW was supported by an NIH-NIAID R01 AI135992. SEJ and HT are supported by H3ABioNet, an initiative of the Human Health and Heredity in Africa Consortium (H3Africa) funded by the National Human Genome Research Institute of the National Institutes of Health under Award Number U24HG006941. The Network for Genomic Surveillance South Africa (NGS-SA) is supported by the Strategic Health Innovation Partnerships Unit of the South African Medical Research Council, with funds received from the South African Department of Science and Innovation. GWH is supported by a grant from the US National Institutes of Health (1U01Al152151-01) {\#}{\#}{\#} Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: No human or animal specimens were used and no ethical clearance was required by the University of Cape Town where the PI of this study was based. All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All Data used was obtained from GISAID (which is credited in the manuscript)},
author = {Martin, Darren P and Weaver, Steven and Tegally, Houryiah and San, Emmanuel James and Shank, Stephen D and Wilkinson, Eduan and Giandhari, Jennifer and Naidoo, Sureshnee and Pillay, Yeshnee and Singh, Lavanya and Lessells, Richard J and Gupta, Ravindra K and Wertheim, Joel O and Nekturenko, Anton and Murrell, Ben and Harkins, Gordon W and Lemey, Philippe and MacLean, Oscar and Robertson, David L and de Oliveira, Tulio and Pond, Sergei L Kosakovsky},
doi = {10.1101/2021.02.23.21252268},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Martin et al. - 2021 - The emergence and ongoing convergent evolution of the N501Y lineages coincides with a major global shift in the S.pdf:pdf},
journal = {medRxiv},
keywords = {OA,genomics{\_}fund{\_}ack,original},
mendeley-tags = {OA,genomics{\_}fund{\_}ack,original},
month = {jul},
pages = {2021.02.23.21252268},
pmid = {33688681},
publisher = {Cold Spring Harbor Laboratory Press},
title = {{The emergence and ongoing convergent evolution of the N501Y lineages coincides with a major global shift in the SARS-CoV-2 selective landscape}},
url = {https://www.medrxiv.org/content/10.1101/2021.02.23.21252268v3 https://www.medrxiv.org/content/10.1101/2021.02.23.21252268v3.abstract},
year = {2021}
}

The emergence and rapid rise in prevalence of three independent SARS-CoV-2 '501Y lineages', B.1.1.7, B.1.351 and P.1, in the last three months of 2020 has prompted renewed concerns about the evolutionarily capacity of SARS-CoV-2 to adapt to both rising population immunity and public health interventions such as vaccines and social distancing. Viruses giving rise to the different 501Y lineages have, presumably under intense natural selection following a shift in host environment, independently acquired multiple unique and convergent mutations. As a consequence all have gained epidemiological and immunological properties that will likely complicate the control of COVID-19. Here, by examining patterns of mutations that arose in SARS-CoV-2 genomes during the pandemic we find evidence of a major change in the selective forces acting on immunologically important SARS-CoV-2 genes (such as N and S) that likely coincided with the emergence of the 501Y lineages. In addition to involving continuing sequence diversification, we find evidence that a significant portion of the ongoing adaptive evolution of the 501Y lineages also involves further convergence between the lineages. Our findings highlight the importance of monitoring how members of these known 501Y lineages, and others still undiscovered, are convergently evolving similar strategies to ensure their persistence in the face of mounting infection and vaccine induced host immune recognition. ### Competing Interest Statement JOW has received funding from Gilead Sciences, LLC (completed) and the CDC (ongoing) via grants and contracts to his institution unrelated to this research. ### Funding Statement DPM is funded by the Wellcome Trust (222574/Z/21/Z) SLKP was supported by the following grants from the U.S. National Institutes of Health R01 AI134384 (NIH/NIAID), R01 AI140970 (NIH/NIAID), and a RAPID award from the US National Science Foundation 2027196 (NSF/DBI,BIO). DLR is funded by the Medical Research Council (MC$\$_UU$\$_1201412) and Wellcome Trust (220977/Z/20/Z). OAM is funded by the Wellcome Trust (206369/Z/17/Z). COG-UK is supported by funding from the Medical Research Council (MRC) part of UK Research & Innovation (UKRI), the National Institute of Health Research (NIHR) and Genome Research Limited, operating as the Wellcome Sanger Institute. PL acknowledges funding from the European Research Council under the European Union's Horizon 2020 research and innovation programme (grant agreement no. 725422-ReservoirDOCS), the EU grant 874850 MOOD and the Wellcome Trust through project 206298/Z/17/Z. JOW was supported by an NIH-NIAID R01 AI135992. SEJ and HT are supported by H3ABioNet, an initiative of the Human Health and Heredity in Africa Consortium (H3Africa) funded by the National Human Genome Research Institute of the National Institutes of Health under Award Number U24HG006941. The Network for Genomic Surveillance South Africa (NGS-SA) is supported by the Strategic Health Innovation Partnerships Unit of the South African Medical Research Council, with funds received from the South African Department of Science and Innovation. GWH is supported by a grant from the US National Institutes of Health (1U01Al152151-01) ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: No human or animal specimens were used and no ethical clearance was required by the University of Cape Town where the PI of this study was based. All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All Data used was obtained from GISAID (which is credited in the manuscript)

@article{Marais2021,
abstract = {The Omicron variant is characterised by more than 50 distinct mutations, the majority of which are located in the spike protein. The implications of these mutations for disease transmission, tissue tropism and diagnostic testing are still to be determined. We evaluated the relative performance of saliva and mid-turbinate swabs as RT-PCR samples for the Delta and Omicron variants. The positive percent agreement (PPA) of saliva swabs and mid-turbinate swabs to a composite standard was 71{\%} (95{\%} CI: 53-84{\%}) and 100{\%} (95{\%} CI: 89-100{\%}), respectively, for the Delta variant. However, for the Omicron variant saliva and mid-turbinate swabs had a 100{\%} (95{\%} CI: 90-100{\%}) and 86{\%} (95{\%} CI: 71-94{\%}) PPA, respectively. This finding supports ex-vivo data of altered tissue tropism from other labs for the Omicron variant. Reassessment of the diagnostic testing standard-of-care may be required as the Omicron variant become the dominant variant worldwide. {\#}{\#}{\#} Competing Interest Statement The authors have declared no competing interest. {\#}{\#}{\#} Funding Statement This research was funded in whole, or in part, by Wellcome [203135/Z16/Z]. For the purpose of Open Access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. This study was funded in whole, or in part, by National Health Laboratory Service in South Africa. {\#}{\#}{\#} Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This research has been approved by the University of Cape Town Human Research Ethics Committee (Ref: 420/2020). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors.},
author = {Marais, Gert and Hsiao, Nei-yuan and Iranzadeh, Arash and Doolabh, Deelan and Enoch, Annabel and Chu, Chun-yat and Williamson, Carolyn and Brink, Adrian and Hardie, Diana},
doi = {10.1101/2021.12.22.21268246},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Marais et al. - 2021 - Saliva swabs are the preferred sample for Omicron detection.pdf:pdf},
journal = {medRxiv},
keywords = {OA,fund{\_}ack},
mendeley-tags = {OA,fund{\_}ack},
month = {dec},
pages = {2021.12.22.21268246},
publisher = {Cold Spring Harbor Laboratory Press},
title = {{Saliva swabs are the preferred sample for Omicron detection}},
url = {https://www.medrxiv.org/content/10.1101/2021.12.22.21268246v1 https://www.medrxiv.org/content/10.1101/2021.12.22.21268246v1.abstract},
year = {2021}
}

The Omicron variant is characterised by more than 50 distinct mutations, the majority of which are located in the spike protein. The implications of these mutations for disease transmission, tissue tropism and diagnostic testing are still to be determined. We evaluated the relative performance of saliva and mid-turbinate swabs as RT-PCR samples for the Delta and Omicron variants. The positive percent agreement (PPA) of saliva swabs and mid-turbinate swabs to a composite standard was 71% (95% CI: 53-84%) and 100% (95% CI: 89-100%), respectively, for the Delta variant. However, for the Omicron variant saliva and mid-turbinate swabs had a 100% (95% CI: 90-100%) and 86% (95% CI: 71-94%) PPA, respectively. This finding supports ex-vivo data of altered tissue tropism from other labs for the Omicron variant. Reassessment of the diagnostic testing standard-of-care may be required as the Omicron variant become the dominant variant worldwide. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This research was funded in whole, or in part, by Wellcome [203135/Z16/Z]. For the purpose of Open Access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. This study was funded in whole, or in part, by National Health Laboratory Service in South Africa. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This research has been approved by the University of Cape Town Human Research Ethics Committee (Ref: 420/2020). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors.

@article{Scheepers2021a,
abstract = {Global genomic surveillance of SARS-CoV-2 has identified variants associated with increased transmissibility, neutralization resistance and disease severity. Here we report the emergence of the PANGO lineage C.1.2, detected at low prevalence in South Africa and eleven other countries. The emergence of C.1.2, associated with a high substitution rate, includes changes within the spike protein that have been associated with increased transmissibility or reduced neutralization sensitivity in SARS-CoV-2 VOC/VOIs. Like Beta and Delta, C.1.2 shows significantly reduced neutralization sensitivity to plasma from vaccinees and individuals infected with the ancestral D614G virus. In contrast, convalescent donors infected with either Beta or Delta showed high plasma neutralization against C.1.2. These functional data suggest that vaccine efficacy against C.1.2 will be equivalent to Beta and Delta, and that prior infection with either Beta or Delta will likely offer protection against C.1.2. {\#}{\#}{\#} Competing Interest Statement The authors have declared no competing interest. {\#}{\#}{\#} Funding Statement The Network for Genomic Surveillance South Africa (NGS-SA) is supported by the Strategic Health Innovation Partnerships Unit of the South African Medical Research Council, with funds received from the South African Department of Science and Innovation. Sequencing activities for the different sequencing hubs were provided by a conditional grant from the South African National Department of Health as part of the emergency COVID-19 response, a cooperative agreement between the National Institute for Communicable Diseases of the National Health Laboratory Service and the United States Centers for Disease Control and Prevention (grant number 5 U01IP001048-05-00); the African Society of Laboratory Medicine (ASLM) and Africa Centers for Disease Control and Prevention through a sub-award from the Bill and Melinda Gates Foundation grant number INV-018978; the UK Foreign, Commonwealth and Development Office and Wellcome (Grant no 221003/Z/20/Z); the South African Medical Research Council (Reference number SHIPNCD 76756); the Department of Health and Social Care and managed by the Fleming Fund and performed under the auspices of the SEQAFRICA project; German Federal Ministry of Education and Research (BMBF; grant number 01KA1606; and G7 collaboration grant with the Robert Koch Institute for COVID19) for the African Network for Improved Diagnostics, Epidemiology and Management of common infectious Agents (ANDEMIA). Hyrax Biosciences Exatype platform was supported by the South African Medical Research Council with funds received from the Department of Science and Innovation. The content and findings reported/illustrated are the sole deduction, view and responsibility of the researcher and do not reflect the official position and sentiments of the SAMRC or the Department of Science and Innovation. This study was supported by the Bill and Melinda Gates award INV-018944 (AS), National Institutes of Health award R01 AI138546 (AS), South African Medical Research Council awards (AS, TdO, PLM) and National Institutes of Health U01 AI151698 for the United World Antivirus Research Network (UWARN) (WVV). SIR is a LOreal/UNESCO Women in Science South African Young Talents awardee. DPM and CW were supported by the Wellcome Trust (222574/Z/21/Z). CW and JB are funded by the EDCTP (RADIATES Consortium; RIA2020EF-3030). PLM is supported by the South African Research Chairs Initiative of the Department of Science and Innovation and the NRF (Grant No 98341) and the Strategic Health Innovations Program of the SA MRC. {\#}{\#}{\#} Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The project was approved by the University of the Witwatersrand Human Research Ethics Committee (HREC) (ref. M180832, M210159, M210752), University of KwaZulu Natal Biomedical Research Ethics Committee (ref. BREC/00001510/2020), Stellenbosch University HREC (ref. N20/04/008{\_}COVID19) and the University of Cape Town HREC (ref. 383/2020) and the University of Pretoria, Faculty of Health human ethics committee, (ref H101 2017). Individual participant consent was not required for the genomic surveillance. This requirement was waived by the Research Ethics Committees. Ethics for the Steve Biko Cohort was approved by the University of Pretoria, Human Research Ethics Committee (Medical) (247/2020). Ethics for the Groote Schuur Hospital was approved by the Human Research Ethics Committee of the Faculty of Health Sciences, University of Cape Town (R021/2020). Ethics for the AZD1222/ChAdOX1 nCOV19 vaccine trial was given approval from the Pan African Clinical Trials Registry (PACTR202006922165132) as well as the South Africa Health Products Regulatory Authority (SAHPRA: 20200407). Ethics approval for the use of the Janssen/Johnson and Johnson Ad26.COV2.S samples were obtained from the Human Research Ethics Committee of the Faculty of Health Sciences, University of the Witwatersrand (M210465). Ethics approval for the use of Pfizer/BioNTech BNT162b2 samples were obtained from the Human Research Ethics Committee of the Faculty of Health Sciences, University of the Witwatersrand (M210465) and approval for the use of these samples was obtained by the Biomedical Research Ethics Committee at the University of KwaZulu Natal (BREC/00001275/2020). All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All SARS-CoV-2 assemblies used in this analysis are deposited in GISAID ({\textless}https://www.gisaid.org/{\textgreater})20,21 and the GISAID accessions are provided in Supplementary Tables 1 and 2. The Nextstrain build of C.1.2 and global sequences will be made available at {\textless}https://nextstrain.org/groups/ngs-sa{\textgreater}. {\textless}https://www.gisaid.org/{\textgreater} {\textless}https://nextstrain.org/groups/ngs-sa{\textgreater}.},
author = {Scheepers, Cathrine and Everatt, Josie and Amoako, Daniel G. and Tegally, Houriiyah and Wibmer, Constantinos Kurt and Mnguni, Anele and Ismail, Arshad and Mahlangu, Boitshoko and Lambson, Bronwen E. and Richardson, Simone I. and Martin, Darren P. and Wilkinson, Eduan and San, James Emmanuel and Giandhari, Jennifer and Manamela, Nelia and Ntuli, Noxolo and Kgagudi, Prudence and Cele, Sandile and Pillay, Sureshnee and Mohale, Thabo and Ramphal, Upasana and Naidoo, Yeshnee and Khumalo, Zamantungwa T. and Kwatra, Gaurav and Gray, Glenda and Bekker, Linda-Gail and Madhi, Shabir A. and Baillie, Vicky and Voorhis, Wesley C. Van and NGS-SA and Treurnicht, Florette K. and Venter, Marietjie and Mlisana, Koleka and Wolter, Nicole and Sigal, Alex and Williamson, Carolyn and Hsiao, Nei-yuan and Msomi, Nokukhanya and Maponga, Tongai and Preiser, Wolfgang and Makatini, Zinhle and Lessells, Richard and Moore, Penny L. and de Oliveira, Tulio and von Gottberg, Anne and Bhiman, Jinal N.},
doi = {10.1101/2021.08.20.21262342},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Scheepers et al. - 2021 - Emergence and phenotypic characterization of C.1.2, a globally detected lineage that rapidly accumulated mutat.pdf:pdf},
journal = {medRxiv},
keywords = {OA,genomics{\_}fund{\_}ack,original},
mendeley-tags = {OA,genomics{\_}fund{\_}ack,original},
month = {sep},
pages = {2021.08.20.21262342},
publisher = {Cold Spring Harbor Laboratory Press},
title = {{Emergence and phenotypic characterization of C.1.2, a globally detected lineage that rapidly accumulated mutations of concern}},
url = {https://www.medrxiv.org/content/10.1101/2021.08.20.21262342v3 https://www.medrxiv.org/content/10.1101/2021.08.20.21262342v3.abstract},
year = {2021}
}

Global genomic surveillance of SARS-CoV-2 has identified variants associated with increased transmissibility, neutralization resistance and disease severity. Here we report the emergence of the PANGO lineage C.1.2, detected at low prevalence in South Africa and eleven other countries. The emergence of C.1.2, associated with a high substitution rate, includes changes within the spike protein that have been associated with increased transmissibility or reduced neutralization sensitivity in SARS-CoV-2 VOC/VOIs. Like Beta and Delta, C.1.2 shows significantly reduced neutralization sensitivity to plasma from vaccinees and individuals infected with the ancestral D614G virus. In contrast, convalescent donors infected with either Beta or Delta showed high plasma neutralization against C.1.2. These functional data suggest that vaccine efficacy against C.1.2 will be equivalent to Beta and Delta, and that prior infection with either Beta or Delta will likely offer protection against C.1.2. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement The Network for Genomic Surveillance South Africa (NGS-SA) is supported by the Strategic Health Innovation Partnerships Unit of the South African Medical Research Council, with funds received from the South African Department of Science and Innovation. Sequencing activities for the different sequencing hubs were provided by a conditional grant from the South African National Department of Health as part of the emergency COVID-19 response, a cooperative agreement between the National Institute for Communicable Diseases of the National Health Laboratory Service and the United States Centers for Disease Control and Prevention (grant number 5 U01IP001048-05-00); the African Society of Laboratory Medicine (ASLM) and Africa Centers for Disease Control and Prevention through a sub-award from the Bill and Melinda Gates Foundation grant number INV-018978; the UK Foreign, Commonwealth and Development Office and Wellcome (Grant no 221003/Z/20/Z); the South African Medical Research Council (Reference number SHIPNCD 76756); the Department of Health and Social Care and managed by the Fleming Fund and performed under the auspices of the SEQAFRICA project; German Federal Ministry of Education and Research (BMBF; grant number 01KA1606; and G7 collaboration grant with the Robert Koch Institute for COVID19) for the African Network for Improved Diagnostics, Epidemiology and Management of common infectious Agents (ANDEMIA). Hyrax Biosciences Exatype platform was supported by the South African Medical Research Council with funds received from the Department of Science and Innovation. The content and findings reported/illustrated are the sole deduction, view and responsibility of the researcher and do not reflect the official position and sentiments of the SAMRC or the Department of Science and Innovation. This study was supported by the Bill and Melinda Gates award INV-018944 (AS), National Institutes of Health award R01 AI138546 (AS), South African Medical Research Council awards (AS, TdO, PLM) and National Institutes of Health U01 AI151698 for the United World Antivirus Research Network (UWARN) (WVV). SIR is a LOreal/UNESCO Women in Science South African Young Talents awardee. DPM and CW were supported by the Wellcome Trust (222574/Z/21/Z). CW and JB are funded by the EDCTP (RADIATES Consortium; RIA2020EF-3030). PLM is supported by the South African Research Chairs Initiative of the Department of Science and Innovation and the NRF (Grant No 98341) and the Strategic Health Innovations Program of the SA MRC. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The project was approved by the University of the Witwatersrand Human Research Ethics Committee (HREC) (ref. M180832, M210159, M210752), University of KwaZulu Natal Biomedical Research Ethics Committee (ref. BREC/00001510/2020), Stellenbosch University HREC (ref. N20/04/008_COVID19) and the University of Cape Town HREC (ref. 383/2020) and the University of Pretoria, Faculty of Health human ethics committee, (ref H101 2017). Individual participant consent was not required for the genomic surveillance. This requirement was waived by the Research Ethics Committees. Ethics for the Steve Biko Cohort was approved by the University of Pretoria, Human Research Ethics Committee (Medical) (247/2020). Ethics for the Groote Schuur Hospital was approved by the Human Research Ethics Committee of the Faculty of Health Sciences, University of Cape Town (R021/2020). Ethics for the AZD1222/ChAdOX1 nCOV19 vaccine trial was given approval from the Pan African Clinical Trials Registry (PACTR202006922165132) as well as the South Africa Health Products Regulatory Authority (SAHPRA: 20200407). Ethics approval for the use of the Janssen/Johnson and Johnson Ad26.COV2.S samples were obtained from the Human Research Ethics Committee of the Faculty of Health Sciences, University of the Witwatersrand (M210465). Ethics approval for the use of Pfizer/BioNTech BNT162b2 samples were obtained from the Human Research Ethics Committee of the Faculty of Health Sciences, University of the Witwatersrand (M210465) and approval for the use of these samples was obtained by the Biomedical Research Ethics Committee at the University of KwaZulu Natal (BREC/00001275/2020). All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All SARS-CoV-2 assemblies used in this analysis are deposited in GISAID (\textlesshttps://www.gisaid.org/\textgreater)20,21 and the GISAID accessions are provided in Supplementary Tables 1 and 2. The Nextstrain build of C.1.2 and global sequences will be made available at \textlesshttps://nextstrain.org/groups/ngs-sa\textgreater. \textlesshttps://www.gisaid.org/\textgreater \textlesshttps://nextstrain.org/groups/ngs-sa\textgreater.

@article{Keeton2021a,
abstract = {The Johnson and Johnson Ad26.COV2.S single-dose vaccine represents an attractive option for coronavirus disease 2019 (COVID-19) vaccination in countries with limited resources. We examined the effect of prior infection with different SARS-CoV-2 variants on Ad26.COV2.S immunogenicity. We compared participants who were SARS-CoV-2 naive with those either infected with the ancestral D614G virus or infected in the second wave when Beta predominated. Prior infection significantly boosts spike-binding antibodies, antibody-dependent cellular cytotoxicity, and neutralizing antibodies against D614G, Beta, and Delta; however, neutralization cross-reactivity varied by wave. Robust CD4 and CD8 T cell responses are induced after vaccination, regardless of prior infection. T cell recognition of variants is largely preserved, apart from some reduction in CD8 recognition of Delta. Thus, Ad26.COV2.S vaccination after infection could result in enhanced protection against COVID-19. The impact of the infecting variant on neutralization breadth after vaccination has implications for the design of second-generation vaccines based on variants of concern.},
author = {Keeton, Roanne and Richardson, Simone I. and Moyo-Gwete, Thandeka and Hermanus, Tandile and Tincho, Marius B. and Benede, Ntombi and Manamela, Nelia P. and Baguma, Richard and Makhado, Zanele and Ngomti, Amkele and Motlou, Thopisang and Mennen, Mathilda and Chinhoyi, Lionel and Skelem, Sango and Maboreke, Hazel and Doolabh, Deelan and Iranzadeh, Arash and Otter, Ashley D. and Brooks, Tim and Noursadeghi, Mahdad and Moon, James C. and Grifoni, Alba and Weiskopf, Daniela and Sette, Alessandro and Blackburn, Jonathan and Hsiao, Nei-Yuan and Williamson, Carolyn and Riou, Catherine and Goga, Ameena and Garrett, Nigel and Bekker, Linda-Gail and Gray, Glenda and Ntusi, Ntobeko A.B. and Moore, Penny L. and Burgers, Wendy A.},
doi = {10.1016/j.chom.2021.10.003},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Keeton et al. - 2021 - Prior infection with SARS-CoV-2 boosts and broadens Ad26.COV2.S immunogenicity in a variant-dependent manner.pdf:pdf},
issn = {19313128},
journal = {Cell Host {\&} Microbe},
keywords = {OA,OA{\_}PMC,fund{\_}ack,genomics{\_}fund{\_}ack,original},
mendeley-tags = {OA,OA{\_}PMC,fund{\_}ack,genomics{\_}fund{\_}ack,original},
month = {nov},
number = {11},
pages = {1611--1619.e5},
pmid = {34688376},
publisher = {Cell Press},
title = {{Prior infection with SARS-CoV-2 boosts and broadens Ad26.COV2.S immunogenicity in a variant-dependent manner}},
url = {https://linkinghub.elsevier.com/retrieve/pii/S1931312821004650},
volume = {29},
year = {2021}
}

The Johnson and Johnson Ad26.COV2.S single-dose vaccine represents an attractive option for coronavirus disease 2019 (COVID-19) vaccination in countries with limited resources. We examined the effect of prior infection with different SARS-CoV-2 variants on Ad26.COV2.S immunogenicity. We compared participants who were SARS-CoV-2 naive with those either infected with the ancestral D614G virus or infected in the second wave when Beta predominated. Prior infection significantly boosts spike-binding antibodies, antibody-dependent cellular cytotoxicity, and neutralizing antibodies against D614G, Beta, and Delta; however, neutralization cross-reactivity varied by wave. Robust CD4 and CD8 T cell responses are induced after vaccination, regardless of prior infection. T cell recognition of variants is largely preserved, apart from some reduction in CD8 recognition of Delta. Thus, Ad26.COV2.S vaccination after infection could result in enhanced protection against COVID-19. The impact of the infecting variant on neutralization breadth after vaccination has implications for the design of second-generation vaccines based on variants of concern.

@article{Moore2021,
author = {Moore, B and Carvajal-L{\'{o}}pez, P and Chauke, P and Cristancho, M and {Dominguez Del Angel}, V and Fernandez-Valverde, S L and Ghouila, A and Gopalasingam, P and Guerfali, F Z and Matimba, A and Morgan, S L and Oliveira, G and Ras, V and Reyes, A and {De Las Rivas}, J and Mulder, Nicola M},
doi = {10.1371/JOURNAL.PCBI.1009218},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Moore et al. - 2021 - Ten simple rules for organizing a bioinformatics training course in low- and middle-income countries.pdf:pdf},
issn = {1553-7358},
journal = {PLOS Computational Biology},
keywords = {Benjamin Moore,Editorial,MEDLINE,NCBI,NIH,NLM,National Center for Biotechnology Information,National Institutes of Health,National Library of Medicine,Nicola Mulder,OA,OA{\_}PMC,PMC8375989,Patricia Carvajal-L{\'{o}}pez,PubMed Abstract,doi:10.1371/journal.pcbi.1009218,editorial,fund{\_}not{\_}ack,pmid:34411091},
mendeley-tags = {OA,OA{\_}PMC,editorial,fund{\_}not{\_}ack},
month = {aug},
number = {8},
pages = {e1009218},
pmid = {34411091},
publisher = {PLoS Comput Biol},
title = {{Ten simple rules for organizing a bioinformatics training course in low- and middle-income countries}},
url = {https://pubmed.ncbi.nlm.nih.gov/34411091/},
volume = {17},
year = {2021}
}

@article{Wilkinson2021b,
abstract = {The progression of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic in Africa has so far been heterogeneous, and the full impact is not yet well understood. In this study, we describe the genomic epidemiology using a dataset of 8746 genomes from 33 African countries and two overseas territories. We show that the epidemics in most countries were initiated by importations predominantly from Europe, which diminished after the early introduction of international travel restrictions. As the pandemic progressed, ongoing transmission in many countries and increasing mobility led to the emergence and spread within the continent of many variants of concern and interest, such as B.1.351, B.1.525, A.23.1, and C.1.1. Although distorted by low sampling numbers and blind spots, the findings highlight that Africa must not be left behind in the global pandemic response, otherwise it could become a source for new variants.},
author = {Wilkinson, Eduan and Giovanetti, Marta and Tegally, Houriiyah and San, James E. and Lessells, Richard and Cuadros, Diego and Martin, Darren P. and Rasmussen, David A. and Zekri, Abdel-Rahman N. and Sangare, Abdoul K. and Ouedraogo, Abdoul-Salam and Sesay, Abdul K. and Priscilla, Abechi and Kemi, Adedotun-Sulaiman and Olubusuyi, Adewunmi M. and Oluwapelumi, Adeyemi O. O. and Hammami, Adn{\`{e}}ne and Amuri, Adrienne A. and Sayed, Ahmad and Ouma, Ahmed E. O. and Elargoubi, Aida and Ajayi, Nnennaya A. and Victoria, Ajogbasile F. and Kazeem, Akano and George, Akpede and Trotter, Alexander J. and Yahaya, Ali A. and Keita, Alpha K. and Diallo, Amadou and Kone, Amadou and Souissi, Amal and Chtourou, Amel and Gutierrez, Ana V. and Page, Andrew J. and Vinze, Anika and Iranzadeh, Arash and Lambisia, Arnold and Ismail, Arshad and Rosemary, Audu and Sylverken, Augustina and Femi, Ayoade and Ibrahimi, Azeddine and Marycelin, Baba and Oderinde, Bamidele S. and Bolajoko, Bankole and Dhaala, Beatrice and Herring, Belinda L. and Njanpop-Lafourcade, Berthe-Marie and Kleinhans, Bronwyn and McInnis, Bronwyn and Tegomoh, Bryan and Brook, Cara and Pratt, Catherine B. and Scheepers, Cathrine and Akoua-Koffi, Chantal G. and Agoti, Charles N. and Peyrefitte, Christophe and Daubenberger, Claudia and Morang'a, Collins M. and Nokes, D. James and Amoako, Daniel G. and Bugembe, Daniel L. and Park, Danny and Baker, David and Doolabh, Deelan and Ssemwanga, Deogratius and Tshiabuila, Derek and Bassirou, Diarra and Amuzu, Dominic S. Y. and Goedhals, Dominique and Omuoyo, Donwilliams O. and Maruapula, Dorcas and Foster-Nyarko, Ebenezer and Lusamaki, Eddy K. and Simulundu, Edgar and Ong'era, Edidah M. and Ngabana, Edith N. and Shumba, Edwin and {El Fahime}, Elmostafa and Lokilo, Emmanuel and Mukantwari, Enatha and Philomena, Eromon and Belarbi, Essia and Simon-Loriere, Etienne and Anoh, Etil{\'{e}} A. and Leendertz, Fabian and Ajili, Faida and Enoch, Fakayode O. and Wasfi, Fares and Abdelmoula, Fatma and Mosha, Fausta S. and Takawira, Faustinos T. and Derrar, Fawzi and Bouzid, Feriel and Onikepe, Folarin and Adeola, Fowotade and Muyembe, Francisca M. and Tanser, Frank and Dratibi, Fred A. and Mbunsu, Gabriel K. and Thilliez, Gaetan and Kay, Gemma L. and Githinji, George and van Zyl, Gert and Awandare, Gordon A. and Schubert, Grit and Maphalala, Gugu P. and Ranaivoson, Hafaliana C. and Lemriss, Hajar and Anise, Happi and Abe, Haruka and Karray, Hela H. and Nansumba, Hellen and Elgahzaly, Hesham A. and Gumbo, Hlanai and Smeti, Ibtihel and Ayed, Ikhlas B. and Odia, Ikponmwosa and {Ben Boubaker}, Ilhem Boutiba and Gaaloul, Imed and Gazy, Inbal and Mudau, Innocent and Ssewanyana, Isaac and Konstantinus, Iyaloo and Lekana-Douk, Jean B. and Makangara, Jean-Claude C. and Tamfum, Jean-Jacques M. and Heraud, Jean-Michel and Shaffer, Jeffrey G. and Giandhari, Jennifer and Li, Jingjing and Yasuda, Jiro and Mends, Joana Q. and Kiconco, Jocelyn and Morobe, John M. and Gyapong, John O. and Okolie, Johnson C. and Kayiwa, John T. and Edwards, Johnathan A. and Gyamfi, Jones and Farah, Jouali and Nakaseegu, Joweria and Ngoi, Joyce M. and Namulondo, Joyce and Andeko, Julia C. and Lutwama, Julius J. and O'Grady, Justin and Siddle, Katherine and Adeyemi, Kayode T. and Tumedi, Kefentse A. and Said, Khadija M. and Hae-Young, Kim and Duedu, Kwabena O. and Belyamani, Lahcen and Fki-Berrajah, Lamia and Singh, Lavanya and Martins, Leonardo de O. and Tyers, Lynn and Ramuth, Magalutcheemee and Mastouri, Maha and Aouni, Mahjoub and el Hefnawi, Mahmoud and Matsheka, Maitshwarelo I. and Kebabonye, Malebogo and Diop, Mamadou and Turki, Manel and Paye, Marietou and Nyaga, Martin M. and Mareka, Mathabo and Damaris, Matoke-Muhia and Mburu, Maureen W. and Mpina, Maximillian and Nwando, Mba and Owusu, Michael and Wiley, Michael R. and Youtchou, Mirabeau T. and Ayekaba, Mitoha O. and Abouelhoda, Mohamed and Seadawy, Mohamed G. and Khalifa, Mohamed K. and Sekhele, Mooko and Ouadghiri, Mouna and Diagne, Moussa M. and Mwenda, Mulenga and Allam, Mushal and Phan, My V. T. and Abid, Nabil and Touil, Nadia and Rujeni, Nadine and Kharrat, Najla and Ismael, Nalia and Dia, Ndongo and Mabunda, Nedio and Hsiao, Nei-yuan and Silochi, Nelson B. and Nsenga, Ngoy and Gumede, Nicksy and Mulder, Nicola and Ndodo, Nnaemeka and Razanajatovo, Norosoa H and Iguosadolo, Nosamiefan and Judith, Oguzie and Kingsley, Ojide C. and Sylvanus, Okogbenin and Peter, Okokhere and Femi, Oladiji and Idowu, Olawoye and Testimony, Olumade and Chukwuma, Omoruyi E. and Ogah, Onwe E. and Onwuamah, Chika K. and Cyril, Oshomah and Faye, Ousmane and Tomori, Oyewale and Ondoa, Pascale and Combe, Patrice and Semanda, Patrick and Oluniyi, Paul E. and Arnaldo, Paulo and Quashie, Peter K. and Dussart, Philippe and Bester, Phillip A. and Mbala, Placide K. and Ayivor-Djanie, Reuben and Njouom, Richard and Phillips, Richard O. and Gorman, Richmond and Kingsley, Robert A. and Carr, Rosina A. A. and {El Kabbaj}, Sa{\^{a}}d and Gargouri, Saba and Masmoudi, Saber and Sankhe, Safietou and Lawal, Salako B. and Kassim, Samar and Trabelsi, Sameh and Metha, Samar and Kammoun, Sami and Lemriss, Sana{\^{a}} and Agwa, Sara H. A. and Calvignac-Spencer, S{\'{e}}bastien and Schaffner, Stephen F. and Doumbia, Seydou and Mandanda, Sheila M. and Aryeetey, Sherihane and Ahmed, Shymaa S. and Elhamoumi, Siham and Andriamandimby, Soafy and Tope, Sobajo and Lekana-Douki, Sonia and Prosolek, Sophie and Ouangraoua, Soumeya and Mundeke, Steve A. and Rudder, Steven and Panji, Sumir and Pillay, Sureshnee and Engelbrecht, Susan and Nabadda, Susan and Behillil, Sylvie and Budiaki, Sylvie L. and van der Werf, Sylvie and Mashe, Tapfumanei and Aanniz, Tarik and Mohale, Thabo and Le-Viet, Thanh and Schindler, Tobias and Anyaneji, Ugochukwu J. and Chinedu, Ugwu and Ramphal, Upasana and Jessica, Uwanibe and George, Uwem and Fonseca, Vagner and Enouf, Vincent and Gorova, Vivianne and Roshdy, Wael H. and Ampofo, William K. and Preiser, Wolfgang and Choga, Wonderful T. and Bediako, Yaw and Naidoo, Yeshnee and Butera, Yvan and de Laurent, Zaydah R. and Sall, Amadou A. and Rebai, Ahmed and von Gottberg, Anne and Kouriba, Bourema and Williamson, Carolyn and Bridges, Daniel J. and Chikwe, Ihekweazu and Bhiman, Jinal N. and Mine, Madisa and Cotten, Matthew and Moyo, Sikhulile and Gaseitsiwe, Simani and Saasa, Ngonda and Sabeti, Pardis C. and Kaleebu, Pontiano and Tebeje, Yenew K. and Tessema, Sofonias K. and Happi, Christian and Nkengasong, John and de Oliveira, Tulio},
doi = {10.1126/science.abj4336},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Wilkinson et al. - 2021 - A year of genomic surveillance reveals how the SARS-CoV-2 pandemic unfolded in Africa.pdf:pdf},
issn = {0036-8075},
journal = {Science},
keywords = {OA,genomics{\_}fund{\_}ack,original},
mendeley-tags = {OA,genomics{\_}fund{\_}ack,original},
month = {oct},
number = {6566},
pages = {423--431},
pmid = {34672751},
publisher = {American Association for the Advancement of Science (AAAS)},
title = {{A year of genomic surveillance reveals how the SARS-CoV-2 pandemic unfolded in Africa}},
url = {https://www.science.org/doi/abs/10.1126/science.abj4336},
volume = {374},
year = {2021}
}

The progression of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic in Africa has so far been heterogeneous, and the full impact is not yet well understood. In this study, we describe the genomic epidemiology using a dataset of 8746 genomes from 33 African countries and two overseas territories. We show that the epidemics in most countries were initiated by importations predominantly from Europe, which diminished after the early introduction of international travel restrictions. As the pandemic progressed, ongoing transmission in many countries and increasing mobility led to the emergence and spread within the continent of many variants of concern and interest, such as B.1.351, B.1.525, A.23.1, and C.1.1. Although distorted by low sampling numbers and blind spots, the findings highlight that Africa must not be left behind in the global pandemic response, otherwise it could become a source for new variants.

@article{Bruyn2021,
abstract = {Objectives To describe the presentation and outcome of SARS-CoV2 infection in an African setting of high non-communicable co-morbidity and also HIV-1 and tuberculosis prevalence. Design Case control analysis with cases stratified by HIV-1 and tuberculosis status. Setting A single-centre observational case-control study of adults admitted to a South African hospital with proven SARS-CoV-2 infection or alternative diagnosis. Participants 104 adults with RT-PCR-proven SARS-CoV2 infection of which 55 (52.9{\%}) were male and 31 (29.8{\%}) HIV-1 co-infected. 40 adults (35.7{\%} male, 30.9{\%} HIV-1 co-infected) admitted during the same period with no RT-PCR or serological evidence of SARS-CoV2 infection and assigned alternative diagnoses. Additional in vitro data from prior studies of 72 healthy controls and 118 HIV-1 uninfected and infected persons participants enrolled to a prior study with either immune evidence of tuberculosis sensitization but no symptoms or microbiologically confirmed pulmonary tuberculosis. Results Two or more co-morbidities were present in 57.7{\%} of 104 RT-PCR proven COVID-19 presentations, the commonest being hypertension (48{\%}), type 2 diabetes mellitus (39{\%}), obesity (31{\%}) but also HIV-1 (30{\%}) and active tuberculosis (14{\%}). Amongst patients dually infected by tuberculosis and SARS-CoV-2, clinical features could be dominated by either SARS-CoV-2 or tuberculosis: lymphopenia was exacerbated, and some markers of inflammation (D-dimer and ferritin) elevated in singly SARS-CoV-2 infected patients were even further elevated (p {\textless} 0.05). HIV-1 and SARS-CoV2 co-infection resulted in lower absolute number and proportion of CD4 lymphocytes, with those in the lowest peripheral CD4 percentage strata exhibiting absent or lower antibody responses against SARS-CoV2. Death occurred in 30/104 (29{\%}) of all COVID-19 patients and in 6/15 (40{\%}) of patients with coincident SARS-CoV-2 and tuberculosis. Conclusions In this South African setting, HIV-1 and tuberculosis are common co-morbidities in patients presenting with COVID-19. In environments in which tuberculosis is common, SARS-CoV-2 and tuberculosis may co-exist with clinical presentation being typical of either disease. Clinical suspicion of exacerbation of co-existent tuberculosis accompanying SARS-CoV-2 should be high. What is already known on this topic? It has been quite widely thought that Africa has been spared the worst effects of the COVID-19 pandemic. There are very few reported case series and no case-control studies comparing COVID-19 patients admitted to hospital to those admitted for other reasons. However several studies have indicated both HIV-1 and tuberculosis co-infection that are endemic in Africa constitute risk factors for poor outcome. In addition Africa is subject to demographic transition and the prevalence of non-communicable co-morbidities such as type 2 diabetes, hypertension and cardiovascular disease is rising rapidly. No study from Africa has described the clinical impact on the presentation of COVID-19 infection. What this study adds Two or more co-morbidities were present in over half COVID-19 presentations, including HIV-1 (30{\%}) and active tuberculosis (14{\%}). Patients dually infected by tuberculosis and SARS-CoV-2, presented as either SARS-CoV-2 or tuberculosis. HIV-1 and SARS-CoV2 co-infection resulted in lower absolute number and proportion of CD4 lymphocytes, and those with low CD4 counts had absent or lower antibody responses against SARS-CoV2. Death occurred 29{\%} of all COVID-19 patients and in 40{\%} of patients with coincident SARS-CoV-2 and tuberculosis. Thus in environments in which tuberculosis is common, SARS-CoV-2 and tuberculosis may co-exist with clinical presentation being typical of either disease and clinical suspicion of exacerbation of co-existent tuberculosis accompanying SARS-CoV-2 should be high. {\#}{\#}{\#} Competing Interest Statement The authors have declared no competing interest. {\#}{\#}{\#} Funding Statement This research was funded in whole, or in part, by Wellcome [104803, 203135, 222754]. For the purpose of Open Access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. RJW was supported by the Francis Crick Institute which receives its core funding from Cancer Research UK (FC0010218), the UK Medical Research Council (FC0010218), and Wellcome (FC0010218). {\#}{\#}{\#} Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study was approved by the University of Cape Town Health Sciences Research Ethical Committee (HREC 207/2020) All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes Data will be made available following formal publication via contact with the corresponding author},
author = {{Du Bruyn}, Elsa and Stek, Cari and Daroowala, Remi and Said-Hartley, Qonita and Hsiao, Marvin and Goliath, Rene T. and Abrahams, Fatima and Jackson, Amanda and Wasserman, Sean and Allwood, Brian W and Davis, Angharad G and Lai, Rachel P-J. and Coussens, Anna K and Wilkinson, Katalin A and de Vries, Jantina and Tiffin, Nicki and Cerrone, Maddalena and Ntusi, Ntobeko A B and Riou, Catherine and Wilkinson, Robert J and Investigators, on behalf of the HIATUS and Aziz, Saalikha and Bangani, Nonzwakazi and Black, John and Bremer, Marise and Burgers, Wendy and Ciko, Zandile and Esmail, Hanif and Gordon, Siamon and Harley, Yolande X R and Lakay, Francisco and Martinez-Estrada, Fernando-Oneissi and Meintjes, Graeme A and Mendelson, Marc and Papavarnavas, Tari and Proust, Alize and Ruzive, Sheena and Schafer, Georgia and Serole, Keboile and Whitaker, Claire and Zvinairo, Kennedy},
doi = {10.1101/2021.05.11.21256479},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Du Bruyn et al. - 2021 - Communicable and non-communicable co-morbidities and the presentation of COVID-19 in an African setting of high.pdf:pdf},
journal = {medRxiv},
keywords = {OA,OA{\_}PMC,fund{\_}ack,genomics{\_}fund{\_}ack,original},
mendeley-tags = {OA,OA{\_}PMC,fund{\_}ack,genomics{\_}fund{\_}ack,original},
month = {may},
pages = {2021.05.11.21256479},
publisher = {Cold Spring Harbor Laboratory Press},
title = {{Communicable and non-communicable co-morbidities and the presentation of COVID-19 in an African setting of high HIV-1 and tuberculosis prevalence}},
url = {https://www.medrxiv.org/content/10.1101/2021.05.11.21256479v1 https://www.medrxiv.org/content/10.1101/2021.05.11.21256479v1.abstract},
year = {2021}
}

Objectives To describe the presentation and outcome of SARS-CoV2 infection in an African setting of high non-communicable co-morbidity and also HIV-1 and tuberculosis prevalence. Design Case control analysis with cases stratified by HIV-1 and tuberculosis status. Setting A single-centre observational case-control study of adults admitted to a South African hospital with proven SARS-CoV-2 infection or alternative diagnosis. Participants 104 adults with RT-PCR-proven SARS-CoV2 infection of which 55 (52.9%) were male and 31 (29.8%) HIV-1 co-infected. 40 adults (35.7% male, 30.9% HIV-1 co-infected) admitted during the same period with no RT-PCR or serological evidence of SARS-CoV2 infection and assigned alternative diagnoses. Additional in vitro data from prior studies of 72 healthy controls and 118 HIV-1 uninfected and infected persons participants enrolled to a prior study with either immune evidence of tuberculosis sensitization but no symptoms or microbiologically confirmed pulmonary tuberculosis. Results Two or more co-morbidities were present in 57.7% of 104 RT-PCR proven COVID-19 presentations, the commonest being hypertension (48%), type 2 diabetes mellitus (39%), obesity (31%) but also HIV-1 (30%) and active tuberculosis (14%). Amongst patients dually infected by tuberculosis and SARS-CoV-2, clinical features could be dominated by either SARS-CoV-2 or tuberculosis: lymphopenia was exacerbated, and some markers of inflammation (D-dimer and ferritin) elevated in singly SARS-CoV-2 infected patients were even further elevated (p \textless 0.05). HIV-1 and SARS-CoV2 co-infection resulted in lower absolute number and proportion of CD4 lymphocytes, with those in the lowest peripheral CD4 percentage strata exhibiting absent or lower antibody responses against SARS-CoV2. Death occurred in 30/104 (29%) of all COVID-19 patients and in 6/15 (40%) of patients with coincident SARS-CoV-2 and tuberculosis. Conclusions In this South African setting, HIV-1 and tuberculosis are common co-morbidities in patients presenting with COVID-19. In environments in which tuberculosis is common, SARS-CoV-2 and tuberculosis may co-exist with clinical presentation being typical of either disease. Clinical suspicion of exacerbation of co-existent tuberculosis accompanying SARS-CoV-2 should be high. What is already known on this topic? It has been quite widely thought that Africa has been spared the worst effects of the COVID-19 pandemic. There are very few reported case series and no case-control studies comparing COVID-19 patients admitted to hospital to those admitted for other reasons. However several studies have indicated both HIV-1 and tuberculosis co-infection that are endemic in Africa constitute risk factors for poor outcome. In addition Africa is subject to demographic transition and the prevalence of non-communicable co-morbidities such as type 2 diabetes, hypertension and cardiovascular disease is rising rapidly. No study from Africa has described the clinical impact on the presentation of COVID-19 infection. What this study adds Two or more co-morbidities were present in over half COVID-19 presentations, including HIV-1 (30%) and active tuberculosis (14%). Patients dually infected by tuberculosis and SARS-CoV-2, presented as either SARS-CoV-2 or tuberculosis. HIV-1 and SARS-CoV2 co-infection resulted in lower absolute number and proportion of CD4 lymphocytes, and those with low CD4 counts had absent or lower antibody responses against SARS-CoV2. Death occurred 29% of all COVID-19 patients and in 40% of patients with coincident SARS-CoV-2 and tuberculosis. Thus in environments in which tuberculosis is common, SARS-CoV-2 and tuberculosis may co-exist with clinical presentation being typical of either disease and clinical suspicion of exacerbation of co-existent tuberculosis accompanying SARS-CoV-2 should be high. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This research was funded in whole, or in part, by Wellcome [104803, 203135, 222754]. For the purpose of Open Access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. RJW was supported by the Francis Crick Institute which receives its core funding from Cancer Research UK (FC0010218), the UK Medical Research Council (FC0010218), and Wellcome (FC0010218). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study was approved by the University of Cape Town Health Sciences Research Ethical Committee (HREC 207/2020) All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes Data will be made available following formal publication via contact with the corresponding author

@article{Riou2021a,
abstract = {SARS-CoV-2 variants have emerged that escape neutralization and potentially impact vaccine efficacy. T cell responses play a role in protection from reinfection and severe disease, but the potential for spike mutations to affect T cell immunity is poorly studied. We assessed both neutralizing antibody and T cell responses in 44 South African COVID-19 patients infected either with B.1.351, now dominant in South Africa, or infected prior to its emergence (‘first wave'), to provide an overall measure of immune evasion. We show for the first time that robust spike-specific CD4 and CD8 T cell responses were detectable in B.1.351-infected patients, similar to first wave patients. Using peptides spanning only the B.1.351 mutated regions, we identified CD4 T cell responses targeting the wild type peptides in 12/22 (54.5{\%}) first wave patients, all of whom failed to recognize corresponding B.1.351-mutated peptides (p=0.0005). However, responses to the mutated regions formed only a small proportion (15.7{\%}) of the overall CD4 response, and few patients (3/44) mounted CD8 responses that targeted the mutated regions. First wave patients showed a 12.7 fold reduction in plasma neutralization of B.1.351. This study shows that despite loss of recognition of immunodominant CD4 epitope(s), overall CD4 and CD8 T cell responses to B.1.351 are preserved. These observations may explain why, despite substantial loss of neutralizing antibody activity against B.1.351, several vaccines have retained the ability to protect against severe COVID-19 disease. One Sentence Summary T cell immunity to SARS-CoV-2 B.1.351 is preserved despite some loss of variant epitope recognition by CD4 T cells. {\#}{\#}{\#} Competing Interest Statement The authors have declared no competing interest. {\#}{\#}{\#} Funding Statement We acknowledge funding from the South African Medical Research Council and the Wellcome Centre for Infectious Diseases Research in Africa (CIDRI-Africa) which is supported by core funding from the Wellcome Trust [203135/Z/16/Z and 222754]. CR and WAB are supported by the EDCTP2 programme of the European Union (EU) Horizon 2020 programme (TMA2017SF-1951-TB-SPEC to CR and TMA2016SF-1535-CaTCH-22 to WAB). CR is further supported by the National Institutes of Health (NIH) (R21AI148027). PLM is supported by the South African Research Chairs Initiative of the Department of Science and Innovation and the National Research Foundation (Grant No 9834). HM is supported by a National Research Foundation Postdoctoral Fellowship (Grant No 129614). RJW is supported by Francis Crick Institute which receives funding from Wellcome (FC0010218), UKRI (FC0010218) and CRUK (FC0010218). CR and RJW also receive support from Rosetrees Trust (M926). The authors or their institutions did not at any time receive payment or services from any other third party for any aspect of the submitted work. {\#}{\#}{\#} Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study was approved by the University of Cape Town Human Research Ethics Committee (HREC: 207/2020 and R021/2020) and electronic or written informed consent was obtained from all participants. All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes The data that support the findings of this study are available from the corresponding authors, WAB and CR, upon reasonable request.},
author = {Riou, Catherine and Keeton, Roanne and Moyo-Gwete, Thandeka and Hermanus, Tandile and Kgagudi, Prudence and Baguma, Richard and Tegally, Houriiyah and Doolabh, Deelan and Iranzadeh, Arash and Tyers, Lynn and Mutavhatsindi, Hygon and Tincho, Marius B and Benede, Ntombi and Marais, Gert and Chinhoyi, Lionel R and Mennen, Mathilda and Skelem, Sango and du Bruyn, Elsa and Stek, Cari and de Oliveira, Tulio and Williamson, Carolyn and Moore, Penny L and Wilkinson, Robert J and {B Ntusi}, Ntobeko A and Burgers, Wendy A},
doi = {10.1101/2021.06.03.21258307},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Riou et al. - 2021 - Loss of recognition of SARS-CoV-2 B.1.351 variant spike epitopes but overall preservation of T cell immunity.pdf:pdf},
journal = {medRxiv},
keywords = {OA,fund{\_}ack,genomics{\_}fund{\_}ack,original},
mendeley-tags = {OA,fund{\_}ack,genomics{\_}fund{\_}ack,original},
month = {jun},
pages = {2021.06.03.21258307},
publisher = {Cold Spring Harbor Laboratory Press},
title = {{Loss of recognition of SARS-CoV-2 B.1.351 variant spike epitopes but overall preservation of T cell immunity}},
url = {https://doi.org/10.1101/2021.06.03.21258307},
year = {2021}
}

SARS-CoV-2 variants have emerged that escape neutralization and potentially impact vaccine efficacy. T cell responses play a role in protection from reinfection and severe disease, but the potential for spike mutations to affect T cell immunity is poorly studied. We assessed both neutralizing antibody and T cell responses in 44 South African COVID-19 patients infected either with B.1.351, now dominant in South Africa, or infected prior to its emergence (‘first wave'), to provide an overall measure of immune evasion. We show for the first time that robust spike-specific CD4 and CD8 T cell responses were detectable in B.1.351-infected patients, similar to first wave patients. Using peptides spanning only the B.1.351 mutated regions, we identified CD4 T cell responses targeting the wild type peptides in 12/22 (54.5%) first wave patients, all of whom failed to recognize corresponding B.1.351-mutated peptides (p=0.0005). However, responses to the mutated regions formed only a small proportion (15.7%) of the overall CD4 response, and few patients (3/44) mounted CD8 responses that targeted the mutated regions. First wave patients showed a 12.7 fold reduction in plasma neutralization of B.1.351. This study shows that despite loss of recognition of immunodominant CD4 epitope(s), overall CD4 and CD8 T cell responses to B.1.351 are preserved. These observations may explain why, despite substantial loss of neutralizing antibody activity against B.1.351, several vaccines have retained the ability to protect against severe COVID-19 disease. One Sentence Summary T cell immunity to SARS-CoV-2 B.1.351 is preserved despite some loss of variant epitope recognition by CD4 T cells. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement We acknowledge funding from the South African Medical Research Council and the Wellcome Centre for Infectious Diseases Research in Africa (CIDRI-Africa) which is supported by core funding from the Wellcome Trust [203135/Z/16/Z and 222754]. CR and WAB are supported by the EDCTP2 programme of the European Union (EU) Horizon 2020 programme (TMA2017SF-1951-TB-SPEC to CR and TMA2016SF-1535-CaTCH-22 to WAB). CR is further supported by the National Institutes of Health (NIH) (R21AI148027). PLM is supported by the South African Research Chairs Initiative of the Department of Science and Innovation and the National Research Foundation (Grant No 9834). HM is supported by a National Research Foundation Postdoctoral Fellowship (Grant No 129614). RJW is supported by Francis Crick Institute which receives funding from Wellcome (FC0010218), UKRI (FC0010218) and CRUK (FC0010218). CR and RJW also receive support from Rosetrees Trust (M926). The authors or their institutions did not at any time receive payment or services from any other third party for any aspect of the submitted work. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study was approved by the University of Cape Town Human Research Ethics Committee (HREC: 207/2020 and R021/2020) and electronic or written informed consent was obtained from all participants. All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes The data that support the findings of this study are available from the corresponding authors, WAB and CR, upon reasonable request.

@article{Richardson2021,
abstract = {SARS-CoV-2 variants of concern (VOCs) exhibit escape from neutralizing antibodies, causing concern about vaccine effectiveness. However, while non-neutralizing cytotoxic functions of antibodies are associated with decreased disease severity and vaccine protection, Fc effector function escape from VOCs is poorly defined. Furthermore, whether VOCs trigger Fc functions with altered specificity, as has been reported for neutralization, is unknown. Here, we demonstrate that the Beta VOC partially evades Fc effector activity in individuals infected with the original (D614G) variant. However, not all functions are equivalently affected, suggesting differential targeting by antibodies mediating distinct Fc functions. Furthermore, Beta infection triggered responses with significantly improved Fc cross-reactivity against global VOCs compared to either D614G infected or Ad26.COV2.S vaccinated individuals. This suggests that, as for neutralization, the infecting spike sequence impacts Fc effector function. These data have important implications for vaccine strategies that incorporate VOCs, suggesting these may induce broader Fc effector responses. {\#}{\#}{\#} Competing Interest Statement The authors have declared no competing interest. {\#}{\#}{\#} Funding Statement W.A.B. is supported by the EDCTP2 programme of the European Unions Horizon 2020 programme (TMA2016SF-1535-CaTCH-22) and Wellcome Centre for Infectious Diseases Research in Africa (CIDRI-Africa), which is supported by core funding from the Wellcome Trust (203135/Z/16/Z). N.A.B.N acknowledges funding from the SA-MRC, MRC UK, NRF and the Lily and Ernst Hausmann Trust. PLM is supported by the South African Research Chairs Initiative of the Department of Science and Innovation and National Research Foundation of South Africa, the SA Medical Research Council SHIP program, the Centre for the AIDS Program of Research (CAPRISA). SIR is a LOreal/UNESCO Women in Science South Africa Young Talents awardee. Related research by the authors is conducted as part of the DST-NRF Centre of Excellence in HIV Prevention, which is supported by the Department of Science and Technology and the National Research Foundation. {\#}{\#}{\#} Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethics approval was received from the University of Pretoria, Human Research Ethics Committee (Medical) (247/2020), the Human Research Ethics Committee of the Faculty of Health Sciences, University of Cape Town (R021/2020). The study was also approved by the University of Cape Town Human Research Ethics Committee (HREC 190/2020 and 209/2020) and the University of the Witwatersrand Human Research Ethics Committee (Medical) (no M210429). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors},
author = {Richardson, Simone I and Manamela, Nelia P and Motsoeneng, Boitumelo M and Kaldine, Haajira and Ayres, Frances and Makhado, Zanele and Mennen, Mathilda and Skelem, Sango and Williams, Noleen and Sullivan, Nancy J and Misasi, John and Gray, Glenda G and Bekker, Linda-Gail and Ueckermann, Veronica and Rossouw, Theresa M and Boswell, Michael T and Ntusi, Ntobeko A B and Burgers, Wendy A and Moore, Penny L},
doi = {10.1101/2021.11.05.21265853},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Richardson et al. - 2021 - A SARS-CoV-2 variant of concern triggers Fc effector function with increased cross-reactivity.pdf:pdf},
journal = {medRxiv},
keywords = {OA,fund{\_}ack,original},
mendeley-tags = {OA,fund{\_}ack,original},
month = {nov},
pages = {2021.11.05.21265853},
publisher = {Cold Spring Harbor Laboratory Press},
title = {{A SARS-CoV-2 variant of concern triggers Fc effector function with increased cross-reactivity}},
url = {https://www.medrxiv.org/content/10.1101/2021.11.05.21265853v1 https://www.medrxiv.org/content/10.1101/2021.11.05.21265853v1.abstract},
year = {2021}
}

SARS-CoV-2 variants of concern (VOCs) exhibit escape from neutralizing antibodies, causing concern about vaccine effectiveness. However, while non-neutralizing cytotoxic functions of antibodies are associated with decreased disease severity and vaccine protection, Fc effector function escape from VOCs is poorly defined. Furthermore, whether VOCs trigger Fc functions with altered specificity, as has been reported for neutralization, is unknown. Here, we demonstrate that the Beta VOC partially evades Fc effector activity in individuals infected with the original (D614G) variant. However, not all functions are equivalently affected, suggesting differential targeting by antibodies mediating distinct Fc functions. Furthermore, Beta infection triggered responses with significantly improved Fc cross-reactivity against global VOCs compared to either D614G infected or Ad26.COV2.S vaccinated individuals. This suggests that, as for neutralization, the infecting spike sequence impacts Fc effector function. These data have important implications for vaccine strategies that incorporate VOCs, suggesting these may induce broader Fc effector responses. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement W.A.B. is supported by the EDCTP2 programme of the European Unions Horizon 2020 programme (TMA2016SF-1535-CaTCH-22) and Wellcome Centre for Infectious Diseases Research in Africa (CIDRI-Africa), which is supported by core funding from the Wellcome Trust (203135/Z/16/Z). N.A.B.N acknowledges funding from the SA-MRC, MRC UK, NRF and the Lily and Ernst Hausmann Trust. PLM is supported by the South African Research Chairs Initiative of the Department of Science and Innovation and National Research Foundation of South Africa, the SA Medical Research Council SHIP program, the Centre for the AIDS Program of Research (CAPRISA). SIR is a LOreal/UNESCO Women in Science South Africa Young Talents awardee. Related research by the authors is conducted as part of the DST-NRF Centre of Excellence in HIV Prevention, which is supported by the Department of Science and Technology and the National Research Foundation. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethics approval was received from the University of Pretoria, Human Research Ethics Committee (Medical) (247/2020), the Human Research Ethics Committee of the Faculty of Health Sciences, University of Cape Town (R021/2020). The study was also approved by the University of Cape Town Human Research Ethics Committee (HREC 190/2020 and 209/2020) and the University of the Witwatersrand Human Research Ethics Committee (Medical) (no M210429). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors

@article{Keeton2021b,
abstract = {The SARS-CoV-2 Omicron variant has multiple Spike (S) protein mutations that contribute to escape from the neutralizing antibody responses, and reducing vaccine protection from infection. The extent to which other components of the adaptive response such as T cells may still target Omicron and contribute to protection from severe outcomes is unknown. We assessed the ability of T cells to react with Omicron spike in participants who were vaccinated with Ad26.CoV2.S or BNT162b2, and in unvaccinated convalescent COVID-19 patients (n = 70). We found that 70-80{\%} of the CD4 and CD8 T cell response to spike was maintained across study groups. Moreover, the magnitude of Omicron cross-reactive T cells was similar to that of the Beta and Delta variants, despite Omicron harbouring considerably more mutations. Additionally, in Omicron-infected hospitalized patients (n = 19), there were comparable T cell responses to ancestral spike, nucleocapsid and membrane proteins to those found in patients hospitalized in previous waves dominated by the ancestral, Beta or Delta variants (n = 49). These results demonstrate that despite Omicron's extensive mutations and reduced susceptibility to neutralizing antibodies, the majority of T cell response, induced by vaccination or natural infection, cross-recognises the variant. Well-preserved T cell immunity to Omicron is likely to contribute to protection from severe COVID-19, supporting early clinical observations from South Africa. {\#}{\#}{\#} Competing Interest Statement A. Sette is a consultant for Gritstone Bio, Flow Pharma, Arcturus Therapeutics, ImmunoScape, CellCarta, Avalia, Moderna, Fortress and Repertoire. All of the other authors declare no competing interests. LJI has filed for patent protection for various aspects of vaccine design and identification of specific epitopes. {\#}{\#}{\#} Funding Statement Research reported in this publication was supported by the South African Medical Research Council (SA-MRC) with funds received from the South African Department of Science and Innovation, including grants 96825, SHIPNCD 76756 and DST/CON 0250/2012. This work was also supported by the Poliomyelitis Research Foundation (21/65) and the Wellcome Centre for Infectious Diseases Research in Africa (CIDRI-Africa), which is supported by core funding from the Wellcome Trust (203135/Z/16/Z and 222574). This project has been funded in whole or in part with Federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under Contract No. 75N93021C00016 to A.S. and Contract No. 75N9301900065 to A.S, D.W. P.L.M. is supported by the South African Research Chairs Initiative of the Department of Science and Innovation and the National Research Foundation (NRF; Grant No 9834). W.A.B. and C.R. are supported by the EDCTP2 programme of the European Union's Horizon 2020 programme (TMA2017SF-1951-TB-SPEC to C.R. and TMA2016SF-1535-CaTCH-22 to W.A.B.). N.A.B.N acknowledges funding from the SA-MRC, MRC UK, NRF and the Lily and Ernst Hausmann Trust. A.S. acknowledges funding from the Bill and Melinda Gates award INV-018944, the NIH (AI138546) and the South African Medical Research Council. R.J.W. acknowledges funding from the Francis Crick Institute, which receives funding from Wellcome FC0010218, UKRI FC0010218 and CRUK FC0010218 and the Rosetrees Trust grant M926 (to C.R. and R.J.W.). For the purposes of open access, the authors have applied a CC-BY public copyright license to any author-accepted version arising from this submission. {\#}{\#}{\#} Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study was approved by the University of Cape Town Human Research Ethics Committee (ref: HREC 190/2020 and 209/2020) and the University of the Witwatersrand Human Research Ethics Committee (Medical) (ref. M210429 and M210752), the Biomedical Research Ethics Committee at the University of KwaZulu-Natal (ref.BREC/00001275/2020) and the University of Pretoria Health Sciences Research Ethics Committee (ref. 247/2020). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors},
author = {Keeton, Roanne and Tincho, Marius B and Ngomti, Amkele and Baguma, Richard and Benede, Ntombi and Suzuki, Akiko and Khan, Khadija and Cele, Sandile and Bernstein, Mallory and Karim, Farina and Madzorera, Sharon V and Moyo-Gwete, Thandeka and Mennen, Mathilda and Skelem, Sango and Adriaanse, Marguerite and Mutithu, Daniel and Aremu, Olukayode and Stek, Cari and du Bruyn, Elsa and {Van Der Mescht}, Mieke A and de Beer, Zelda and de Villiers, Talita R and Bodenstein, Annie and van den Berg, Gretha and Mendes, Adriano and Strydom, Amy and Venter, Marietjie and Grifoni, Alba and Weiskopf, Daniela and Sette, Alessandro and Wilkinson, Robert J and Bekker, Linda-Gail and Gray, Glenda and Ueckermann, Veronica and Rossouw, Theresa and Boswell, Michael T and Bihman, Jinal and Moore, Penny L and Sigal, Alex and Ntusi, Ntobeko A B and Burgers, Wendy A and Riou, Catherine},
doi = {10.1101/2021.12.26.21268380},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Keeton et al. - 2021 - SARS-CoV-2 spike T cell responses induced upon vaccination or infection remain robust against Omicron.pdf:pdf},
journal = {medRxiv},
keywords = {OA,fund{\_}ack,genomics{\_}fund{\_}ack,original},
mendeley-tags = {OA,fund{\_}ack,genomics{\_}fund{\_}ack,original},
month = {dec},
pages = {2021.12.26.21268380},
publisher = {Cold Spring Harbor Laboratory Press},
title = {{SARS-CoV-2 spike T cell responses induced upon vaccination or infection remain robust against Omicron}},
url = {https://www.medrxiv.org/content/10.1101/2021.12.26.21268380v1 https://www.medrxiv.org/content/10.1101/2021.12.26.21268380v1.abstract},
year = {2021}
}

The SARS-CoV-2 Omicron variant has multiple Spike (S) protein mutations that contribute to escape from the neutralizing antibody responses, and reducing vaccine protection from infection. The extent to which other components of the adaptive response such as T cells may still target Omicron and contribute to protection from severe outcomes is unknown. We assessed the ability of T cells to react with Omicron spike in participants who were vaccinated with Ad26.CoV2.S or BNT162b2, and in unvaccinated convalescent COVID-19 patients (n = 70). We found that 70-80% of the CD4 and CD8 T cell response to spike was maintained across study groups. Moreover, the magnitude of Omicron cross-reactive T cells was similar to that of the Beta and Delta variants, despite Omicron harbouring considerably more mutations. Additionally, in Omicron-infected hospitalized patients (n = 19), there were comparable T cell responses to ancestral spike, nucleocapsid and membrane proteins to those found in patients hospitalized in previous waves dominated by the ancestral, Beta or Delta variants (n = 49). These results demonstrate that despite Omicron's extensive mutations and reduced susceptibility to neutralizing antibodies, the majority of T cell response, induced by vaccination or natural infection, cross-recognises the variant. Well-preserved T cell immunity to Omicron is likely to contribute to protection from severe COVID-19, supporting early clinical observations from South Africa. ### Competing Interest Statement A. Sette is a consultant for Gritstone Bio, Flow Pharma, Arcturus Therapeutics, ImmunoScape, CellCarta, Avalia, Moderna, Fortress and Repertoire. All of the other authors declare no competing interests. LJI has filed for patent protection for various aspects of vaccine design and identification of specific epitopes. ### Funding Statement Research reported in this publication was supported by the South African Medical Research Council (SA-MRC) with funds received from the South African Department of Science and Innovation, including grants 96825, SHIPNCD 76756 and DST/CON 0250/2012. This work was also supported by the Poliomyelitis Research Foundation (21/65) and the Wellcome Centre for Infectious Diseases Research in Africa (CIDRI-Africa), which is supported by core funding from the Wellcome Trust (203135/Z/16/Z and 222574). This project has been funded in whole or in part with Federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under Contract No. 75N93021C00016 to A.S. and Contract No. 75N9301900065 to A.S, D.W. P.L.M. is supported by the South African Research Chairs Initiative of the Department of Science and Innovation and the National Research Foundation (NRF; Grant No 9834). W.A.B. and C.R. are supported by the EDCTP2 programme of the European Union's Horizon 2020 programme (TMA2017SF-1951-TB-SPEC to C.R. and TMA2016SF-1535-CaTCH-22 to W.A.B.). N.A.B.N acknowledges funding from the SA-MRC, MRC UK, NRF and the Lily and Ernst Hausmann Trust. A.S. acknowledges funding from the Bill and Melinda Gates award INV-018944, the NIH (AI138546) and the South African Medical Research Council. R.J.W. acknowledges funding from the Francis Crick Institute, which receives funding from Wellcome FC0010218, UKRI FC0010218 and CRUK FC0010218 and the Rosetrees Trust grant M926 (to C.R. and R.J.W.). For the purposes of open access, the authors have applied a CC-BY public copyright license to any author-accepted version arising from this submission. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study was approved by the University of Cape Town Human Research Ethics Committee (ref: HREC 190/2020 and 209/2020) and the University of the Witwatersrand Human Research Ethics Committee (Medical) (ref. M210429 and M210752), the Biomedical Research Ethics Committee at the University of KwaZulu-Natal (ref.BREC/00001275/2020) and the University of Pretoria Health Sciences Research Ethics Committee (ref. 247/2020). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors

@article{Tegally2021,
abstract = {The Beta variant of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in South Africa in late 2020 and rapidly became the dominant variant, causing over 95{\%} of infections in the country during and after the second epidemic wave. Here we show rapid replacement of the Beta variant by the Delta variant, a highly transmissible variant of concern (VOC) that emerged in India and subsequently spread around the world. The Delta variant was imported to South Africa primarily from India, spread rapidly in large monophyletic clusters to all provinces, and became dominant within three months of introduction. This was associated with a resurgence in community transmission, leading to a third wave which was associated with a high number of deaths. We estimated a growth advantage for the Delta variant in South Africa of 0.089 (95{\%} confidence interval [CI] 0.084-0.093) per day which corresponds to a transmission advantage of 46{\%} (95{\%} CI 44-48) compared to the Beta variant. These data provide additional support for the increased transmissibility of the Delta variant relative to other VOC and highlight how dynamic shifts in the distribution of variants contribute to the ongoing public health threat. {\#}{\#}{\#} Competing Interest Statement The authors have declared no competing interest. {\#}{\#}{\#} Funding Statement This research reported in this publication was supported by the Strategic Health Innovation Partnerships Unit of the South African Medical Research Council, with funds received from the South African Department of Science and Innovation (DSI). Genomics Surveillance in South Africa was supported in part through National Institutes of Health USA grant U01 AI151698 for the United World Antiviral Research Network (UWARN) and by the Rockefeller Foundation (Prof. Tulio de Oliveira and Dr. Eduan Wilkinson). CERI and KRISP have received donations from Chan Soon-Shiong Family Foundation (CSSFF) and Illumina . CW is funded by the South African MRC; Wellcome Trust (2222574/Z/21/Z) and the EDCTP (RADIATES Consortium; RIA2020EF-3030) {\#}{\#}{\#} Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The genomic surveillance was approved by the University of KwaZuluNatal Biomedical Research Ethics Committee (ref. BREC/00001510/2020), the University of the Witwatersrand Human Research Ethics Committee (HREC, ref. M180832, M210159, M210752), Stellenbosch University HREC (ref. N20/04/008{\_}COVID19), and the University of Cape Town HREC (ref. 383/2020), the University of Pretoria HREC (100/2017), and the University of Free State Health Sciences Research Ethics Committee (ref. UFS HSD2020/1860/2710). Individual participant consent was not required for genomic surveillance, this requirement was waived by the Research Ethics Committees. Following sequencing, all consensus sequences are uploaded to GISAID33 and their use is subject to the database terms and conditions. All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All sequence data is public at GISAID. Short reads (i.e. FastQ files) are available at the Short Read Archive of the NCBI. [htts://www.ceri.org.za][1] [1]: https://www.ceri.org.za},
author = {Tegally, Houriiyah and Wilkinson, Eduan and Althaus, Christian L and Giovanetti, Marta and San, James Emmanuel and Giandhari, Jennifer and Pillay, Sureshnee and Naidoo, Yeshnee and Ramphal, Upasana and Msomi, Nokukhanya and Mlisana, Koleka and Amoako, Daniel G and Everatt, Josie and Mohale, Thabo and Nguni, Anele and Mahlangu, Boitshoko and Ntuli, Noxolo and Khumalo, Zamantungwa T and Makatini, Zinhle and Wolter, Nicole and Scheepers, Cathrine and Ismail, Arshad and Doolabh, Deelan and Joseph, Rageema and Strydom, Amy and Mendes, Adriano and Davis, Michaela and Mayaphi, Simnikiwe H and Ramphal, Yajna and Maharaj, Arisha and Karim, Wasim Abdool and Tshiabuila, Derek and Anyaneji, Ugochukwu J and Singh, Lavanya and Engelbrecht, Susan and Fonseca, Vagner and Marais, Kruger and Korsman, Stephen and Hardie, Diana and Hsiao, Nei-yuan and Maponga, Tongai and van Zyl, Gert and Marais, Gert and Iranzadeh, Arash and Martin, Darren and Alcantara, Luiz Carlos Junior and Bester, Phillip Armand and Nyaga, Martin M and Subramoney, Kathleen and Treurnicht, Florette K and Venter, Marietjie and Goedhals, Dominique and Preiser, Wolfgang and Bhiman, Jinal N and von Gottberg, Anne and Williamson, Carolyn and Lessells, Richard J and de Oliveira, Tulio},
doi = {10.1101/2021.09.23.21264018},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Tegally et al. - 2021 - Rapid replacement of the Beta variant by the Delta variant in South Africa.pdf:pdf},
journal = {medRxiv},
keywords = {OA,genomics{\_}fund{\_}ack,original},
mendeley-tags = {OA,genomics{\_}fund{\_}ack,original},
month = {sep},
pages = {2021.09.23.21264018},
publisher = {Cold Spring Harbor Laboratory Press},
title = {{Rapid replacement of the Beta variant by the Delta variant in South Africa}},
url = {https://www.medrxiv.org/content/10.1101/2021.09.23.21264018v1 https://www.medrxiv.org/content/10.1101/2021.09.23.21264018v1.abstract},
year = {2021}
}

The Beta variant of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in South Africa in late 2020 and rapidly became the dominant variant, causing over 95% of infections in the country during and after the second epidemic wave. Here we show rapid replacement of the Beta variant by the Delta variant, a highly transmissible variant of concern (VOC) that emerged in India and subsequently spread around the world. The Delta variant was imported to South Africa primarily from India, spread rapidly in large monophyletic clusters to all provinces, and became dominant within three months of introduction. This was associated with a resurgence in community transmission, leading to a third wave which was associated with a high number of deaths. We estimated a growth advantage for the Delta variant in South Africa of 0.089 (95% confidence interval [CI] 0.084-0.093) per day which corresponds to a transmission advantage of 46% (95% CI 44-48) compared to the Beta variant. These data provide additional support for the increased transmissibility of the Delta variant relative to other VOC and highlight how dynamic shifts in the distribution of variants contribute to the ongoing public health threat. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This research reported in this publication was supported by the Strategic Health Innovation Partnerships Unit of the South African Medical Research Council, with funds received from the South African Department of Science and Innovation (DSI). Genomics Surveillance in South Africa was supported in part through National Institutes of Health USA grant U01 AI151698 for the United World Antiviral Research Network (UWARN) and by the Rockefeller Foundation (Prof. Tulio de Oliveira and Dr. Eduan Wilkinson). CERI and KRISP have received donations from Chan Soon-Shiong Family Foundation (CSSFF) and Illumina . CW is funded by the South African MRC; Wellcome Trust (2222574/Z/21/Z) and the EDCTP (RADIATES Consortium; RIA2020EF-3030) ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The genomic surveillance was approved by the University of KwaZuluNatal Biomedical Research Ethics Committee (ref. BREC/00001510/2020), the University of the Witwatersrand Human Research Ethics Committee (HREC, ref. M180832, M210159, M210752), Stellenbosch University HREC (ref. N20/04/008_COVID19), and the University of Cape Town HREC (ref. 383/2020), the University of Pretoria HREC (100/2017), and the University of Free State Health Sciences Research Ethics Committee (ref. UFS HSD2020/1860/2710). Individual participant consent was not required for genomic surveillance, this requirement was waived by the Research Ethics Committees. Following sequencing, all consensus sequences are uploaded to GISAID33 and their use is subject to the database terms and conditions. All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All sequence data is public at GISAID. Short reads (i.e. FastQ files) are available at the Short Read Archive of the NCBI. [htts://www.ceri.org.za][1] [1]: https://www.ceri.org.za

@article{Keeton2021,
abstract = {The Johnson and Johnson Ad26.COV2.S single dose vaccine, designed as an emergency response to the pandemic, represents an attractive option for the scale-up of COVID-19 vaccination in resource-limited countries. We examined the effect of prior infection with ancestral (D614G) or Beta variants on Ad26.COV2.S immunogenicity approximately 28 days post-vaccination. We compared healthcare workers who were SARS-CoV-2 naive (n=20), to those infected during the first wave prior to the emergence of Beta (n=20), and those infected in the second wave (n=20), when Beta was the dominant variant. We demonstrate that a priming exposure from infection significantly increased the magnitude of spike binding antibodies, neutralizing antibodies and antibody-dependent cellular cytotoxicity activity (ADCC) against D614G, Beta and Delta variants. The magnitude of antibody boosting was similar in both waves, despite the longer time interval between wave 1 infection and vaccination (7 months), compared to wave 2 (2 months). ADCC and binding cross-reactivity was similar in both waves. However, neutralization cross-reactivity varied by wave, showing that the antibody repertoire was shaped by the spike sequence of the infecting variant. Robust CD4 and CD8 T cell responses to spike of similar or higher magnitude as those elicited by infection were induced after vaccination. In contrast to antibody responses, prior infection was not required for the generation of high magnitude T cell responses, and T cell recognition of the Beta variant was fully preserved. Therefore, Ad26.COV2.S vaccination following prior infection, even {\textgreater}6 months previously, may result in substantially enhanced protection against COVID-19, of particular relevance in settings of high SARS-CoV-2 seroprevalence. Furthermore, the dominant impact of the infecting variant on neutralization breadth after vaccination has important implications for the design of second-generation vaccines based on variants of concern. {\#}{\#}{\#} Competing Interest Statement The authors have declared no competing interest. {\#}{\#}{\#} Funding Statement Research reported in this publication was supported by the South African Medical Research Council (SA-MRC) with funds received from the South African Department of Science and Innovation, including grants 96825, SHIPNCD 76756 and DST/CON 0250/2012. This work was also supported by the Poliomyelitis Research Foundation (21/65) and the Wellcome Centre for Infectious Diseases Research in Africa (CIDRI-Africa), which is supported by core funding from the Wellcome Trust (203135/Z/16/Z and 222754). P.L.M. and S.I.R. are supported by the South African Research Chairs Initiative of the Department of Science and Innovation and the National Research Foundation (NRF; Grant No 9834). S.I.R. is a LOreal/UNESCO Women in Science South Africa Young Talents awardee. W.A.B. and C.R. are supported by the EDCTP2 programme of the European Unions Horizon 2020 programme (TMA2017SF-1951-TB-SPEC to C.R. and TMA2016SF-1535-CaTCH-22 to W.A.B.). N.A.B.N acknowledges funding from the SA-MRC, MRC UK, NRF and the Lily and Ernst Hausmann Trust. M.N. is supported by the Wellcome Trust (207511/Z/17/Z) and by NIHR Biomedical Research Funding to University College London Hospitals. {\#}{\#}{\#} Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study was approved by the University of Cape Town Human Research Ethics Committee (HREC 190/2020 and 209/2020) and the University of the Witwatersrand Human Research Ethics Committee (Medical) (no M210429). All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data referred to in the manuscript is available in the manuscript or Supplementary files.},
author = {Keeton, Roanne and Richardson, Simone I and Moyo-Gwete, Thandeka and Hermanus, Tandile and Tincho, Marius B and Benede, Ntombi and Manamela, Nelia P and Baguma, Richard and Makhado, Zanele and Ngomti, Amkele and Motlou, Thopisang and Mennen, Mathilda and Chinoyi, Lionel and Skelem, Sango and Maboreke, Hazel and Doolabh, Deelan and Iranzadeh, Arash and Otter, Ashley and Brooks, Tim and Noursadeghi, Mahdad and Moon, James and Blackburn, Jonathan and Hsiao, Nei-Yuan and Williamson, Carolyn and Riou, Catherine and Goga, Ameena and Garrett, Nigel and Bekker, Linda-Gail and Gray, Glenda and Ntusi, Ntobeko A.B and Moore, Penny L and Burgers, Wendy A},
doi = {10.1101/2021.07.24.21261037},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Keeton et al. - 2021 - Prior infection with SARS-CoV-2 boosts and broadens Ad26.COV2.S immunogenicity in a variant dependent manner.pdf:pdf},
journal = {medRxiv},
keywords = {OA,OA{\_}PMC,fund{\_}ack,genomics{\_}fund{\_}ack,original},
mendeley-tags = {OA,OA{\_}PMC,fund{\_}ack,genomics{\_}fund{\_}ack,original},
month = {jul},
pages = {2021.07.24.21261037},
publisher = {Cold Spring Harbor Laboratory Press},
title = {{Prior infection with SARS-CoV-2 boosts and broadens Ad26.COV2.S immunogenicity in a variant dependent manner}},
url = {https://www.medrxiv.org/content/10.1101/2021.07.24.21261037v1 https://www.medrxiv.org/content/10.1101/2021.07.24.21261037v1.abstract},
year = {2021}
}

The Johnson and Johnson Ad26.COV2.S single dose vaccine, designed as an emergency response to the pandemic, represents an attractive option for the scale-up of COVID-19 vaccination in resource-limited countries. We examined the effect of prior infection with ancestral (D614G) or Beta variants on Ad26.COV2.S immunogenicity approximately 28 days post-vaccination. We compared healthcare workers who were SARS-CoV-2 naive (n=20), to those infected during the first wave prior to the emergence of Beta (n=20), and those infected in the second wave (n=20), when Beta was the dominant variant. We demonstrate that a priming exposure from infection significantly increased the magnitude of spike binding antibodies, neutralizing antibodies and antibody-dependent cellular cytotoxicity activity (ADCC) against D614G, Beta and Delta variants. The magnitude of antibody boosting was similar in both waves, despite the longer time interval between wave 1 infection and vaccination (7 months), compared to wave 2 (2 months). ADCC and binding cross-reactivity was similar in both waves. However, neutralization cross-reactivity varied by wave, showing that the antibody repertoire was shaped by the spike sequence of the infecting variant. Robust CD4 and CD8 T cell responses to spike of similar or higher magnitude as those elicited by infection were induced after vaccination. In contrast to antibody responses, prior infection was not required for the generation of high magnitude T cell responses, and T cell recognition of the Beta variant was fully preserved. Therefore, Ad26.COV2.S vaccination following prior infection, even \textgreater6 months previously, may result in substantially enhanced protection against COVID-19, of particular relevance in settings of high SARS-CoV-2 seroprevalence. Furthermore, the dominant impact of the infecting variant on neutralization breadth after vaccination has important implications for the design of second-generation vaccines based on variants of concern. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement Research reported in this publication was supported by the South African Medical Research Council (SA-MRC) with funds received from the South African Department of Science and Innovation, including grants 96825, SHIPNCD 76756 and DST/CON 0250/2012. This work was also supported by the Poliomyelitis Research Foundation (21/65) and the Wellcome Centre for Infectious Diseases Research in Africa (CIDRI-Africa), which is supported by core funding from the Wellcome Trust (203135/Z/16/Z and 222754). P.L.M. and S.I.R. are supported by the South African Research Chairs Initiative of the Department of Science and Innovation and the National Research Foundation (NRF; Grant No 9834). S.I.R. is a LOreal/UNESCO Women in Science South Africa Young Talents awardee. W.A.B. and C.R. are supported by the EDCTP2 programme of the European Unions Horizon 2020 programme (TMA2017SF-1951-TB-SPEC to C.R. and TMA2016SF-1535-CaTCH-22 to W.A.B.). N.A.B.N acknowledges funding from the SA-MRC, MRC UK, NRF and the Lily and Ernst Hausmann Trust. M.N. is supported by the Wellcome Trust (207511/Z/17/Z) and by NIHR Biomedical Research Funding to University College London Hospitals. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study was approved by the University of Cape Town Human Research Ethics Committee (HREC 190/2020 and 209/2020) and the University of the Witwatersrand Human Research Ethics Committee (Medical) (no M210429). All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data referred to in the manuscript is available in the manuscript or Supplementary files.

@article{Fendler2021,
abstract = {Patients with cancer have higher COVID-19 morbidity and mortality. Here we present the prospective CAPTURE study, integrating longitudinal immune profiling with clinical annotation. Of 357 patients with cancer, 118 were SARS-CoV-2 positive, 94 were symptomatic and 2 died of COVID-19. In this cohort, 83{\%} patients had S1-reactive antibodies and 82{\%} had neutralizing antibodies against wild type SARS-CoV-2, whereas neutralizing antibody titers against the Alpha, Beta and Delta variants were substantially reduced. S1-reactive antibody levels decreased in 13{\%} of patients, whereas neutralizing antibody titers remained stable for up to 329 days. Patients also had detectable SARS-CoV-2-specific T cells and CD4+ responses correlating with S1-reactive antibody levels, although patients with hematological malignancies had impaired immune responses that were disease and treatment specific, but presented compensatory cellular responses, further supported by clinical recovery in all but one patient. Overall, these findings advance the understanding of the nature and duration of the immune response to SARS-CoV-2 in patients with cancer. Turajlic and colleagues assess longitudinal antibody and cellular immune responses against SARS-CoV-2 variants of concern in patients with cancer, following either recovery from SARS-CoV-2 infection or vaccination, in two back-to-back reports from the CAPTURE study.},
author = {Fendler, Annika and Au, Lewis and Shepherd, Scott T C and Byrne, Fiona and Cerrone, Maddalena and Boos, Laura Amanda and Rzeniewicz, Karolina and Gordon, William and Shum, Benjamin and Gerard, Camille L and Ward, Barry and Xie, Wenyi and Schmitt, Andreas M and Joharatnam-Hogan, Nalinie and Cornish, Georgina H and Pule, Martin and Mekkaoui, Leila and Ng, Kevin W and Carlyle, Eleanor and Edmonds, Kim and Rosario, Lyra Del and Sarker, Sarah and Lingard, Karla and Mangwende, Mary and Holt, Lucy and Ahmod, Hamid and Stone, Richard and Gomes, Camila and Flynn, Helen R. and Agua-Doce, Ana and Hobson, Philip and Caidan, Simon and Howell, Michael and Wu, Mary and Goldstone, Robert and Crawford, Margaret and Cubitt, Laura and Patel, Harshil and Gavrielides, Mike and Nye, Emma and Snijders, Ambrosius P and MacRae, James I and Nicod, Jerome and Gronthoud, Firza and Shea, Robyn L and Messiou, Christina and Cunningham, David and Chau, Ian and Starling, Naureen and Turner, Nicholas and Welsh, Liam and van As, Nicholas and Jones, Robin L and Droney, Joanne and Banerjee, Susana and Tatham, Kate C and Jhanji, Shaman and O'Brien, Mary and Curtis, Olivia and Harrington, Kevin and Bhide, Shreerang and Bazin, Jessica and Robinson, Anna and Stephenson, Clemency and Slattery, Tim and Khan, Yasir and Tippu, Zayd and Leslie, Isla and Gennatas, Spyridon and Okines, Alicia and Reid, Alison and Young, Kate and Furness, Andrew J S and Pickering, Lisa and Gandhi, Sonia and Gamblin, Steve and Swanton, Charles and Nicholson, Emma and Kumar, Sacheen and Yousaf, Nadia and Wilkinson, Katalin A and Swerdlow, Anthony and Harvey, Ruth and Kassiotis, George and Larkin, James and Wilkinson, Robert J and Turajlic, Samra},
doi = {10.1038/s43018-021-00275-9},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Fendler et al. - 2021 - Functional antibody and T cell immunity following SARS-CoV-2 infection, including by variants of concern, in pat.pdf:pdf},
issn = {2662-1347},
journal = {Nature Cancer},
keywords = {2,Cancer,CoV,OA,SARS,Viral infection,fund{\_}ack,genomics{\_}fund{\_}ack,original},
mendeley-tags = {OA,fund{\_}ack,genomics{\_}fund{\_}ack,original},
month = {oct},
pages = {1321--1337},
publisher = {Nature Publishing Group},
title = {{Functional antibody and T cell immunity following SARS-CoV-2 infection, including by variants of concern, in patients with cancer: the CAPTURE study}},
url = {https://www.nature.com/articles/s43018-021-00275-9},
volume = {2},
year = {2021}
}

Patients with cancer have higher COVID-19 morbidity and mortality. Here we present the prospective CAPTURE study, integrating longitudinal immune profiling with clinical annotation. Of 357 patients with cancer, 118 were SARS-CoV-2 positive, 94 were symptomatic and 2 died of COVID-19. In this cohort, 83% patients had S1-reactive antibodies and 82% had neutralizing antibodies against wild type SARS-CoV-2, whereas neutralizing antibody titers against the Alpha, Beta and Delta variants were substantially reduced. S1-reactive antibody levels decreased in 13% of patients, whereas neutralizing antibody titers remained stable for up to 329 days. Patients also had detectable SARS-CoV-2-specific T cells and CD4+ responses correlating with S1-reactive antibody levels, although patients with hematological malignancies had impaired immune responses that were disease and treatment specific, but presented compensatory cellular responses, further supported by clinical recovery in all but one patient. Overall, these findings advance the understanding of the nature and duration of the immune response to SARS-CoV-2 in patients with cancer. Turajlic and colleagues assess longitudinal antibody and cellular immune responses against SARS-CoV-2 variants of concern in patients with cancer, following either recovery from SARS-CoV-2 infection or vaccination, in two back-to-back reports from the CAPTURE study.

@article{Fendler2021a,
abstract = {Coronavirus disease 2019 (COVID-19) antiviral response in a pan-tumor immune monitoring (CAPTURE) ( NCT03226886 ) is a prospective cohort study of COVID-19 immunity in patients with cancer. Here we evaluated 585 patients following administration of two doses of BNT162b2 or AZD1222 vaccines, administered 12 weeks apart. Seroconversion rates after two doses were 85{\%} and 59{\%} in patients with solid and hematological malignancies, respectively. A lower proportion of patients had detectable titers of neutralizing antibodies (NAbT) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOC) versus wild-type (WT) SARS-CoV-2. Patients with hematological malignancies were more likely to have undetectable NAbT and had lower median NAbT than those with solid cancers against both SARS-CoV-2 WT and VOC. By comparison with individuals without cancer, patients with hematological, but not solid, malignancies had reduced neutralizing antibody (NAb) responses. Seroconversion showed poor concordance with NAbT against VOC. Previous SARS-CoV-2 infection boosted the NAb response including against VOC, and anti-CD20 treatment was associated with undetectable NAbT. Vaccine-induced T cell responses were detected in 80{\%} of patients and were comparable between vaccines or cancer types. Our results have implications for the management of patients with cancer during the ongoing COVID-19 pandemic. Turajlic and colleagues assess longitudinal antibody and cellular immune responses against SARS-CoV-2 variants of concern in patients with cancer, following either recovery from SARS-CoV-2 infection or vaccination, in two back-to-back reports from the CAPTURE study.},
author = {Fendler, Annika and Shepherd, Scott T C and Au, Lewis and Wilkinson, Katalin A and Wu, Mary and Byrne, Fiona and Cerrone, Maddalena and Schmitt, Andreas M and Joharatnam-Hogan, Nalinie and Shum, Benjamin and Tippu, Zayd and Rzeniewicz, Karolina and Boos, Laura Amanda and Harvey, Ruth and Carlyle, Eleanor and Edmonds, Kim and {Del Rosario}, Lyra and Sarker, Sarah and Lingard, Karla and Mangwende, Mary and Holt, Lucy and Ahmod, Hamid and Korteweg, Justine and Foley, Tara and Bazin, Jessica and Gordon, William and Barber, Taja and Emslie-Henry, Andrea and Xie, Wenyi and Gerard, Camille L and Deng, Daqi and Wall, Emma C and Agua-Doce, Ana and Namjou, Sina and Caidan, Simon and Gavrielides, Mike and MacRae, James I and Kelly, Gavin and Peat, Kema and Kelly, Denise and Murra, Aida and Kelly, Kayleigh and O'Flaherty, Molly and Dowdie, Lauren and Ash, Natalie and Gronthoud, Firza and Shea, Robyn L and Gardner, Gail and Murray, Darren and Kinnaird, Fiona and Cui, Wanyuan and Pascual, Javier and Rodney, Simon and Mencel, Justin and Curtis, Olivia and Stephenson, Clemency and Robinson, Anna and Oza, Bhavna and Farag, Sheima and Leslie, Isla and Rogiers, Aljosja and Iyengar, Sunil and Ethell, Mark and Messiou, Christina and Cunningham, David and Chau, Ian and Starling, Naureen and Turner, Nicholas and Welsh, Liam and van As, Nicholas and Jones, Robin L and Droney, Joanne and Banerjee, Susana and Tatham, Kate C and O'Brien, Mary and Harrington, Kevin and Bhide, Shreerang and Okines, Alicia and Reid, Alison and Young, Kate and Furness, Andrew J S and Pickering, Lisa and Swanton, Charles and Gandhi, Sonia and Gamblin, Steve and Bauer, David L V and Kassiotis, George and Kumar, Sacheen and Yousaf, Nadia and Jhanji, Shaman and Nicholson, Emma and Howell, Michael and Walker, Susanna and Wilkinson, Robert J and Larkin, James and Turajlic, Samra},
doi = {10.1038/s43018-021-00274-w},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Fendler et al. - 2021 - Adaptive immunity and neutralizing antibodies against SARS-CoV-2 variants of concern following vaccination in pa.pdf:pdf},
issn = {2662-1347},
journal = {Nature Cancer},
keywords = {2,Cancer,CoV,Medical research,OA,OA{\_}PMC,SARS,Vaccines,fund{\_}ack,genomics{\_}fund{\_}ack,original},
mendeley-tags = {OA,OA{\_}PMC,fund{\_}ack,genomics{\_}fund{\_}ack,original},
month = {oct},
pages = {1305--1320},
pmid = {34950880},
publisher = {Nature Publishing Group},
title = {{Adaptive immunity and neutralizing antibodies against SARS-CoV-2 variants of concern following vaccination in patients with cancer: the CAPTURE study}},
url = {https://www.nature.com/articles/s43018-021-00274-w},
volume = {2},
year = {2021}
}

Coronavirus disease 2019 (COVID-19) antiviral response in a pan-tumor immune monitoring (CAPTURE) ( NCT03226886 ) is a prospective cohort study of COVID-19 immunity in patients with cancer. Here we evaluated 585 patients following administration of two doses of BNT162b2 or AZD1222 vaccines, administered 12 weeks apart. Seroconversion rates after two doses were 85% and 59% in patients with solid and hematological malignancies, respectively. A lower proportion of patients had detectable titers of neutralizing antibodies (NAbT) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOC) versus wild-type (WT) SARS-CoV-2. Patients with hematological malignancies were more likely to have undetectable NAbT and had lower median NAbT than those with solid cancers against both SARS-CoV-2 WT and VOC. By comparison with individuals without cancer, patients with hematological, but not solid, malignancies had reduced neutralizing antibody (NAb) responses. Seroconversion showed poor concordance with NAbT against VOC. Previous SARS-CoV-2 infection boosted the NAb response including against VOC, and anti-CD20 treatment was associated with undetectable NAbT. Vaccine-induced T cell responses were detected in 80% of patients and were comparable between vaccines or cancer types. Our results have implications for the management of patients with cancer during the ongoing COVID-19 pandemic. Turajlic and colleagues assess longitudinal antibody and cellular immune responses against SARS-CoV-2 variants of concern in patients with cancer, following either recovery from SARS-CoV-2 infection or vaccination, in two back-to-back reports from the CAPTURE study.

@article{Davis2021a,
abstract = {Neurological manifestations of COVID-19 are increasingly described in the literature. There is uncertainty whether these occur due to direct neuroinvasion of the virus, para-infectious immunopathology, as result of systemic complications of disease such as hypercoagulability or due to a combination of these mechanisms. Here we describe clinical and radiological manifestations in a sequential cohort of patients presenting to a district hospital in South Africa with neurological symptoms with and without confirmed COVID-19 during the first peak of the epidemic. In these patients, where symptoms suggestive of meningitis and encephalitis were most common, thorough assessment of presence in CSF via PCR for SARS-CoV2 did not explain neurological presentations, notwithstanding very high rates of COVID-19 admissions. Although an understanding of potential neurotropic mechanisms remains an important area of research, these results provide rationale for greater focus towards the understanding of para-immune pathogenic processes and the contribution of systemic coagulopathy and their interaction with pre-existing risk factors in order to better manage neurological disease in the context of COVID-19. These results also inform the clinician that consideration of an alternative diagnosis and treatment for neurological presentations in this context is crucial, even in the patient with a confirmed diagnosis COVID-19. {\#}{\#}{\#} Competing Interest Statement The authors have declared no competing interest. {\#}{\#}{\#} Funding Statement AGD is supported through a UCL Wellcome Trust PhD Programme for Clinicians Fellowship (award number 175479). GS received funding through the EDCTP2 (TMA2018SF-2446 - KSHV/HIV morbidity). RJW receives support from Francis Crick Institute which is funded by UKRI (FC0010218); Wellcome (FC0010218) and CRUK (FC0010218). He is additionally supported EDCTP (RIA2017T-2019 109237). This research was funded in whole, or in part, by the Wellcome Trust [Grant numbers 203135/Z/16/Z, 104803; 203135; 222574]. For the purpose of open access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission {\#}{\#}{\#} Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study was approved by the Faculty of Health Sciences Human Research Ethical Committee of the University of Cape Town (HREC 207/2020) and by the ethical review board at Livingstone Hospital. All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes Data archived},
author = {Davis, Angharad G and Bremer, Marise and Sch{\"{a}}fer, Georgia and Dixon, Luke and Abrahams, Fatima and Goliath, Rene T and Maxebengula, Mpumi and Proust, Alize and Chavda, Anesh and Black, John and Wilkinson, Robert J},
doi = {10.1101/2021.05.14.21254691},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Davis et al. - 2021 - Spectrum of neurological manifestations and systematic evaluation of cerebrospinal fluid for SARS-CoV2 in patients.pdf:pdf},
journal = {medRxiv},
keywords = {OA,fund{\_}ack,original},
mendeley-tags = {OA,fund{\_}ack,original},
month = {may},
pages = {2021.05.14.21254691},
publisher = {Cold Spring Harbor Laboratory Press},
title = {{Spectrum of neurological manifestations and systematic evaluation of cerebrospinal fluid for SARS-CoV2 in patients admitted to hospital during the COVID-19 epidemic in South Africa}},
url = {https://doi.org/10.1101/2021.05.14.21254691},
year = {2021}
}

Neurological manifestations of COVID-19 are increasingly described in the literature. There is uncertainty whether these occur due to direct neuroinvasion of the virus, para-infectious immunopathology, as result of systemic complications of disease such as hypercoagulability or due to a combination of these mechanisms. Here we describe clinical and radiological manifestations in a sequential cohort of patients presenting to a district hospital in South Africa with neurological symptoms with and without confirmed COVID-19 during the first peak of the epidemic. In these patients, where symptoms suggestive of meningitis and encephalitis were most common, thorough assessment of presence in CSF via PCR for SARS-CoV2 did not explain neurological presentations, notwithstanding very high rates of COVID-19 admissions. Although an understanding of potential neurotropic mechanisms remains an important area of research, these results provide rationale for greater focus towards the understanding of para-immune pathogenic processes and the contribution of systemic coagulopathy and their interaction with pre-existing risk factors in order to better manage neurological disease in the context of COVID-19. These results also inform the clinician that consideration of an alternative diagnosis and treatment for neurological presentations in this context is crucial, even in the patient with a confirmed diagnosis COVID-19. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement AGD is supported through a UCL Wellcome Trust PhD Programme for Clinicians Fellowship (award number 175479). GS received funding through the EDCTP2 (TMA2018SF-2446 - KSHV/HIV morbidity). RJW receives support from Francis Crick Institute which is funded by UKRI (FC0010218); Wellcome (FC0010218) and CRUK (FC0010218). He is additionally supported EDCTP (RIA2017T-2019 109237). This research was funded in whole, or in part, by the Wellcome Trust [Grant numbers 203135/Z/16/Z, 104803; 203135; 222574]. For the purpose of open access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study was approved by the Faculty of Health Sciences Human Research Ethical Committee of the University of Cape Town (HREC 207/2020) and by the ethical review board at Livingstone Hospital. All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes Data archived

@article{Riou2021,
abstract = {ABSTRACT T cells are involved in control of COVID-19, but limited knowledge is available on the relationship between antigen-specific T cell response and disease severity. Here, we assessed the magnitude, function and phenotype of SARS-CoV-2-specific CD4 T cells in 95 hospitalized COVID-19 patients (38 of them being HIV-1 and/or tuberculosis (TB) co-infected) and 38 non-COVID-19 patients, using flow cytometry. We showed that SARS-CoV-2-specific CD4 T cell attributes, rather than magnitude, associates with disease severity, with severe disease being characterized by poor polyfunctional potential, reduced proliferation capacity and enhanced HLA-DR expression. Moreover, HIV-1 and TB co-infection skewed the SARS-CoV-2 T cell response. HIV-1 mediated CD4 T cell depletion associated with suboptimal T cell and humoral immune responses to SARS-CoV-2; and a decrease in the polyfunctional capacity of SARS-CoV-2-specific CD4 T cells was observed in COVID-19 patients with active TB. Our results also revealed that COVID-19 patients displayed reduced frequency of Mtb-specific CD4 T cells, with possible implications for TB disease progression.},
author = {Riou, Catherine and {Du Bruyn}, Elsa and Stek, Cari and Daroowala, Remy and Goliath, Rene T and Abrahams, Fatima and Said-Hartley, Qonita and Allwood, Brian W. and Hsiao, Nei-Yuan and Wilkinson, Katalin A. and {Lindestam Arlehamn}, Cecilia S. and Sette, Alessandro and Wasserman, Sean and Wilkinson, Robert J},
doi = {10.1172/JCI149125},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Riou et al. - 2021 - Relationship of SARS-CoV-2-specific CD4 response to COVID-19 severity and impact of HIV-1 and tuberculosis co-infec.pdf:pdf;:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Riou et al. - 2021 - Relationship of SARS-CoV-2-specific CD4 response to COVID-19 severity and impact of HIV-1 and tuberculosis co-in(2).pdf:pdf},
issn = {1558-8238},
journal = {Journal of Clinical Investigation},
keywords = {OA,OA{\_}PMC,fund{\_}ack,genomics{\_}fund{\_}ack,original},
mendeley-tags = {OA,OA{\_}PMC,fund{\_}ack,genomics{\_}fund{\_}ack,original},
month = {may},
number = {12},
pages = {e149125},
pmid = {33945513},
publisher = {American Society for Clinical Investigation},
title = {{Relationship of SARS-CoV-2-specific CD4 response to COVID-19 severity and impact of HIV-1 and tuberculosis co-infection}},
url = {http://www.jci.org/articles/view/149125},
volume = {131},
year = {2021}
}

ABSTRACT T cells are involved in control of COVID-19, but limited knowledge is available on the relationship between antigen-specific T cell response and disease severity. Here, we assessed the magnitude, function and phenotype of SARS-CoV-2-specific CD4 T cells in 95 hospitalized COVID-19 patients (38 of them being HIV-1 and/or tuberculosis (TB) co-infected) and 38 non-COVID-19 patients, using flow cytometry. We showed that SARS-CoV-2-specific CD4 T cell attributes, rather than magnitude, associates with disease severity, with severe disease being characterized by poor polyfunctional potential, reduced proliferation capacity and enhanced HLA-DR expression. Moreover, HIV-1 and TB co-infection skewed the SARS-CoV-2 T cell response. HIV-1 mediated CD4 T cell depletion associated with suboptimal T cell and humoral immune responses to SARS-CoV-2; and a decrease in the polyfunctional capacity of SARS-CoV-2-specific CD4 T cells was observed in COVID-19 patients with active TB. Our results also revealed that COVID-19 patients displayed reduced frequency of Mtb-specific CD4 T cells, with possible implications for TB disease progression.

@article{Viana2021,
abstract = {The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic in southern Africa has been characterised by three distinct waves. The first was associated with a mix of SARS-CoV-2 lineages, whilst the second and third waves were driven by the Beta and Delta variants respectively[1][1]–[3][2]. In November 2021, genomic surveillance teams in South Africa and Botswana detected a new SARS-CoV-2 variant associated with a rapid resurgence of infections in Gauteng Province, South Africa. Within three days of the first genome being uploaded, it was designated a variant of concern (Omicron) by the World Health Organization and, within three weeks, had been identified in 87 countries. The Omicron variant is exceptional for carrying over 30 mutations in the spike glycoprotein, predicted to influence antibody neutralization and spike function[4][3]. Here, we describe the genomic profile and early transmission dynamics of Omicron, highlighting the rapid spread in regions with high levels of population immunity. {\#}{\#}{\#} Competing Interest Statement The authors have declared no competing interest. {\#}{\#}{\#} Funding Statement The research reported in this publication was supported by the Strategic Health Innovation Partnerships Unit of the South African Medical Research Council, with funds received from the South African Department of Science and Innovation. CA received funding from the European Union Horizon 2020 research and innovation programme project EpiPose (No 101003688). DPM was funded by the Wellcome Trust (222574/Z/21/Z). RC {\&} AR acknowledge support from the Wellcome Trust (Collaborators Award 206298/Z/17/Z ARTIC network) and AR from the European Research Council (grant agreement number 725422 ReservoirDOCS). VH was supported by the Biotechnology and Biological Sciences Research Council (BBSRC) (grant number BB/M010996/1). AEZ, JT, MUGK, OGP acknowledge support from the Oxford Martin School. MUGK acknowledges support from the Rockefeller Foundation, Google.org, and the European Horizon 2020 programme MOOD ({\#}874850). MV and the ZARV members, UP was funded through the ANDEMIA G7 Global Health Concept: contributions to improvement of International Health, COVID19 funds through the Robert Koch Institute. The genomic sequencing at UCT/NHLS is funded from the South African Medical Research Council and Department of Science and Innovation; and by the Wellcome Centre for Infectious Diseases Research in Africa (CIDRI Africa) which is supported by core funding from the Wellcome Trust [203135/Z/16/Z and 222754]. CW and JNB are funded by the EDCTP (RADIATES Consortium; RIA2020EF 3030). Sequencing activities at the NICD were supported by: a conditional grant from the South African National Department of Health as part of the emergency COVID 19 response; a cooperative agreement between the National Institute for Communicable Diseases of the National Health Laboratory Service and the United States Centers for Disease Control and Prevention (grant number 5 U01IP001048 05 00); the African Society of Laboratory Medicine (ASLM) and Africa Centers for Disease Control and Prevention through a sub award from the Bill and Melinda Gates Foundation grant number INV 018978; the UK Foreign, Commonwealth and Development Office and Wellcome (Grant no 221003/Z/20/Z); the South African Medical Research Council (Reference number SHIPNCD 76756); the UK Department of Health and Social Care, managed by the Fleming Fund and performed under the auspices of the SEQAFRICA project. The genomic sequencing in Botswana was supported by the Foundation for Innovative New Diagnostics and Fogarty International Center (5D43TW009610), NIH (5K24AI131924 04; 5K24AI131928 05), as well in kind support from the Botswana government through the Ministry of Health {\&} Wellness and Presidential COVID 19 Task Force. SM was supported in part by the Bill {\&} Melinda Gates Foundation [036530]. {\#}{\#}{\#} Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The genomic surveillance in South Africa was approved by the University of KwaZulu Natal Biomedical Research Ethics Committee (BREC/00001510/2020), the University of the Witwatersrand Human Research Ethics Committee (HREC) (M180832), Stellenbosch University HREC (N20/04/008{\_}COVID-19), University of Cape Town HREC (383/2020), University of Pretoria HREC (H101/17) and the University of the Free State Health Sciences Research Ethics Committee (UFS HSD2020/1860/2710). The genomic sequencing in Botswana was conductedas part of the national vaccine roll-out plan and was approved by the Health Research and Development Committee (Health Research Ethics body, HRDC{\#}00948 and HRDC{\#}00904). Individual participant consent was not required for the genomic surveillance. This requirement was waived by the Research Ethics Committees. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All genomes generated in this research at public available at GISAID. The short reads are public available at the Short Read Archives of NCBI. [1]: {\#}ref-1 [2]: {\#}ref-3 [3]: {\#}ref-4},
author = {Viana, Raquel and Moyo, Sikhulile and Amoako, Daniel G and Tegally, Houriiyah and Scheepers, Cathrine and Althaus, Christian L and Anyaneji, Ugochukwu J and Bester, Phillip A and Boni, Maciej F and Chand, Mohammed and Choga, Wonderful T and Colquhoun, Rachel and Davids, Michaela and Deforche, Koen and Doolabh, Deelan and Engelbrecht, Susan and Everatt, Josie and Giandhari, Jennifer and Giovanetti, Marta and Hardie, Diana and Hill, Verity and Hsiao, Nei-Yuan and Iranzadeh, Arash and Ismail, Arshad and Joseph, Charity and Joseph, Rageema and Koopile, Legodile and Pond, Sergei L Kosakovsky and Kraemer, Moritz U G and Kuate-Lere, Lesego and Laguda-Akingba, Oluwakemi and Lesetedi-Mafoko, Onalethatha and Lessells, Richard J and Lockman, Shahin and Lucaci, Alexander G and Maharaj, Arisha and Mahlangu, Boitshoko and Maponga, Tongai and Mahlakwane, Kamela and Makatini, Zinhle and Marais, Gert and Maruapula, Dorcas and Masupu, Kereng and Matshaba, Mogomotsi and Mayaphi, Simnikiwe and Mbhele, Nokuzola and Mbulawa, Mpaphi B and Mendes, Adriano and Mlisana, Koleka and Mnguni, Anele and Mohale, Thabo and Moir, Monika and Moruisi, Kgomotso and Mosepele, Mosepele and Motsatsi, Gerald and Motswaledi, Modisa S and Mphoyakgosi, Thongbotho and Msomi, Nokukhanya and Mwangi, Peter N and Naidoo, Yeshnee and Ntuli, Noxolo and Nyaga, Martin and Olubayo, Lucier and Pillay, Sureshnee and Radibe, Botshelo and Ramphal, Yajna and Ramphal, Upasana and San, James E and Scott, Lesley and Shapiro, Roger and Singh, Lavanya and Smith-Lawrence, Pamela and Stevens, Wendy and Strydom, Amy and Subramoney, Kathleen and Tebeila, Naume and Tshiabuila, Derek and Tsui, Joseph and van Wyk, Stephanie and Weaver, Steven and Wibmer, Constantinos K and Wilkinson, Eduan and Wolter, Nicole and Zarebski, Alexander E and Zuze, Boitumelo and Goedhals, Dominique and Preiser, Wolfgang and Treurnicht, Florette and Venter, Marietje and Williamson, Carolyn and Pybus, Oliver G and Bhiman, Jinal and Glass, Allison and Martin, Darren P and Rambaut, Andrew and Gaseitsiwe, Simani and von Gottberg, Anne and de Oliveira, Tulio},
doi = {10.1101/2021.12.19.21268028},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Viana et al. - 2021 - Rapid epidemic expansion of the SARS-CoV-2 Omicron variant in southern Africa.pdf:pdf},
journal = {medRxiv},
keywords = {OA,fund{\_}ack,genomics{\_}fund{\_}ack,original},
mendeley-tags = {OA,fund{\_}ack,genomics{\_}fund{\_}ack,original},
month = {dec},
pages = {2021.12.19.21268028},
publisher = {Cold Spring Harbor Laboratory Press},
title = {{Rapid epidemic expansion of the SARS-CoV-2 Omicron variant in southern Africa}},
url = {https://www.medrxiv.org/content/10.1101/2021.12.19.21268028v1 https://www.medrxiv.org/content/10.1101/2021.12.19.21268028v1.abstract},
year = {2021}
}

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic in southern Africa has been characterised by three distinct waves. The first was associated with a mix of SARS-CoV-2 lineages, whilst the second and third waves were driven by the Beta and Delta variants respectively[1][1]–[3][2]. In November 2021, genomic surveillance teams in South Africa and Botswana detected a new SARS-CoV-2 variant associated with a rapid resurgence of infections in Gauteng Province, South Africa. Within three days of the first genome being uploaded, it was designated a variant of concern (Omicron) by the World Health Organization and, within three weeks, had been identified in 87 countries. The Omicron variant is exceptional for carrying over 30 mutations in the spike glycoprotein, predicted to influence antibody neutralization and spike function[4][3]. Here, we describe the genomic profile and early transmission dynamics of Omicron, highlighting the rapid spread in regions with high levels of population immunity. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement The research reported in this publication was supported by the Strategic Health Innovation Partnerships Unit of the South African Medical Research Council, with funds received from the South African Department of Science and Innovation. CA received funding from the European Union Horizon 2020 research and innovation programme project EpiPose (No 101003688). DPM was funded by the Wellcome Trust (222574/Z/21/Z). RC & AR acknowledge support from the Wellcome Trust (Collaborators Award 206298/Z/17/Z ARTIC network) and AR from the European Research Council (grant agreement number 725422 ReservoirDOCS). VH was supported by the Biotechnology and Biological Sciences Research Council (BBSRC) (grant number BB/M010996/1). AEZ, JT, MUGK, OGP acknowledge support from the Oxford Martin School. MUGK acknowledges support from the Rockefeller Foundation, Google.org, and the European Horizon 2020 programme MOOD (#874850). MV and the ZARV members, UP was funded through the ANDEMIA G7 Global Health Concept: contributions to improvement of International Health, COVID19 funds through the Robert Koch Institute. The genomic sequencing at UCT/NHLS is funded from the South African Medical Research Council and Department of Science and Innovation; and by the Wellcome Centre for Infectious Diseases Research in Africa (CIDRI Africa) which is supported by core funding from the Wellcome Trust [203135/Z/16/Z and 222754]. CW and JNB are funded by the EDCTP (RADIATES Consortium; RIA2020EF 3030). Sequencing activities at the NICD were supported by: a conditional grant from the South African National Department of Health as part of the emergency COVID 19 response; a cooperative agreement between the National Institute for Communicable Diseases of the National Health Laboratory Service and the United States Centers for Disease Control and Prevention (grant number 5 U01IP001048 05 00); the African Society of Laboratory Medicine (ASLM) and Africa Centers for Disease Control and Prevention through a sub award from the Bill and Melinda Gates Foundation grant number INV 018978; the UK Foreign, Commonwealth and Development Office and Wellcome (Grant no 221003/Z/20/Z); the South African Medical Research Council (Reference number SHIPNCD 76756); the UK Department of Health and Social Care, managed by the Fleming Fund and performed under the auspices of the SEQAFRICA project. The genomic sequencing in Botswana was supported by the Foundation for Innovative New Diagnostics and Fogarty International Center (5D43TW009610), NIH (5K24AI131924 04; 5K24AI131928 05), as well in kind support from the Botswana government through the Ministry of Health & Wellness and Presidential COVID 19 Task Force. SM was supported in part by the Bill & Melinda Gates Foundation [036530]. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The genomic surveillance in South Africa was approved by the University of KwaZulu Natal Biomedical Research Ethics Committee (BREC/00001510/2020), the University of the Witwatersrand Human Research Ethics Committee (HREC) (M180832), Stellenbosch University HREC (N20/04/008_COVID-19), University of Cape Town HREC (383/2020), University of Pretoria HREC (H101/17) and the University of the Free State Health Sciences Research Ethics Committee (UFS HSD2020/1860/2710). The genomic sequencing in Botswana was conductedas part of the national vaccine roll-out plan and was approved by the Health Research and Development Committee (Health Research Ethics body, HRDC#00948 and HRDC#00904). Individual participant consent was not required for the genomic surveillance. This requirement was waived by the Research Ethics Committees. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All genomes generated in this research at public available at GISAID. The short reads are public available at the Short Read Archives of NCBI. [1]: #ref-1 [2]: #ref-3 [3]: #ref-4

@article{Kitchin2021,
abstract = {The Janssen (Johnson {\&} Johnson) Ad26.COV2.S non-replicating viral vector vaccine, which requires only a single dose and conventional cold chain storage, is a valuable tool for COVID-19 vaccination programs in resource-limited settings. Here we show that neutralizing and binding responses to Ad26.COV2.S vaccination are stable for 6-months post-vaccination, with responses highest against the ancestral vaccine-similar D614G variant. Secondly, using longitudinal samples from individuals who experienced clinically mild breakthrough infections 3-4 months after vaccination, we show dramatically boosted binding antibodies, Fc effector function and neutralization. These responses, which are cross-reactive against diverse SARS-CoV-2 variants and SARS-CoV-1, are of similar magnitude to humoral immune responses measured in severely ill, hospitalized donors. These data highlight the significant priming capacity of Ad26.COV2.S, and have implications for population immunity in areas where the single dose Ad26.COV2.S vaccine has been deployed. {\#}{\#}{\#} Competing Interest Statement The authors have declared no competing interest. {\#}{\#}{\#} Funding Statement This study was funded by the South African Medical Research Council (grants 96825 and 96838). P.L.M. is supported by the South African Research Chairs Initiative of the Department of Science and Innovation and the National Research Foundation of South Africa (grant no. 98341). W.A.B. is supported by the EDCTP2 programme of the European Unions Horizon 2020 programme (TMA2016SF-1535-CaTCH-22), the Wellcome Centre for Infectious Diseases Research in Africa (CIDRI-Africa) which is supported by core funding from the Wellcome Trust (203135/Z/16/Z) and the Poliomyelitis Research Foundation (PRF 21/65). N.A.B.N acknowledges funding from the SAMRC, MRC UK, NRF and the Lily and Ernst Hausmann Trust. S.I.R. is a LOreal/UNESCO Women in Science South Africa Young Talents awardee. Related research by the authors is conducted as part of the DST-NRF Centre of Excellence in HIV Prevention, which is supported by the South African Department of Science and Technology and the National Research Foundation. {\#}{\#}{\#} Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Human Research Ethics Committees of the University of the Witwatersrand (ethics reference number: M210465), University of Pretoria (ethics reference number: 247/2020) and University of Cape Town (ethics reference numbers: 190/2020 and 209/2020) gave ethical approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors.},
author = {Kitchin, Dale and Richardson, Simone I and van der Mescht, Mieke A and Motlou, Thopisang and Mzindle, Nonkululeko and Moyo-Gwete, Thandeka and Makhado, Zanele and Ayres, Frances and Manamela, Nelia P and Spencer, Holly and Lambson, Bronwen and Oosthuysen, Brent and Mennen, Mathilda and Skelem, Sango and Williams, Noleen and Ntusi, Ntobeko A B and Burgers, Wendy A and Gray, Glenda G and Bekker, Linda-Gail and Boswell, Michael T and Rossouw, Theresa M and Ueckermann, Veronica and Moore, Penny L},
doi = {10.1101/2021.11.08.21266049},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Kitchin et al. - 2021 - Ad26.COV2.S breakthrough infections induce high titers of antibodies capable of neutralizing variants of concern.pdf:pdf},
journal = {medRxiv},
keywords = {OA,fund{\_}ack,original},
mendeley-tags = {OA,fund{\_}ack,original},
month = {nov},
pages = {2021.11.08.21266049},
publisher = {Cold Spring Harbor Laboratory Press},
title = {{Ad26.COV2.S breakthrough infections induce high titers of antibodies capable of neutralizing variants of concern}},
url = {https://www.medrxiv.org/content/10.1101/2021.11.08.21266049v1 https://www.medrxiv.org/content/10.1101/2021.11.08.21266049v1.abstract},
year = {2021}
}

The Janssen (Johnson & Johnson) Ad26.COV2.S non-replicating viral vector vaccine, which requires only a single dose and conventional cold chain storage, is a valuable tool for COVID-19 vaccination programs in resource-limited settings. Here we show that neutralizing and binding responses to Ad26.COV2.S vaccination are stable for 6-months post-vaccination, with responses highest against the ancestral vaccine-similar D614G variant. Secondly, using longitudinal samples from individuals who experienced clinically mild breakthrough infections 3-4 months after vaccination, we show dramatically boosted binding antibodies, Fc effector function and neutralization. These responses, which are cross-reactive against diverse SARS-CoV-2 variants and SARS-CoV-1, are of similar magnitude to humoral immune responses measured in severely ill, hospitalized donors. These data highlight the significant priming capacity of Ad26.COV2.S, and have implications for population immunity in areas where the single dose Ad26.COV2.S vaccine has been deployed. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study was funded by the South African Medical Research Council (grants 96825 and 96838). P.L.M. is supported by the South African Research Chairs Initiative of the Department of Science and Innovation and the National Research Foundation of South Africa (grant no. 98341). W.A.B. is supported by the EDCTP2 programme of the European Unions Horizon 2020 programme (TMA2016SF-1535-CaTCH-22), the Wellcome Centre for Infectious Diseases Research in Africa (CIDRI-Africa) which is supported by core funding from the Wellcome Trust (203135/Z/16/Z) and the Poliomyelitis Research Foundation (PRF 21/65). N.A.B.N acknowledges funding from the SAMRC, MRC UK, NRF and the Lily and Ernst Hausmann Trust. S.I.R. is a LOreal/UNESCO Women in Science South Africa Young Talents awardee. Related research by the authors is conducted as part of the DST-NRF Centre of Excellence in HIV Prevention, which is supported by the South African Department of Science and Technology and the National Research Foundation. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Human Research Ethics Committees of the University of the Witwatersrand (ethics reference number: M210465), University of Pretoria (ethics reference number: 247/2020) and University of Cape Town (ethics reference numbers: 190/2020 and 209/2020) gave ethical approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors.

@article{Valley-Omar2021,
abstract = {Routine SARS-CoV-2 surveillance in the Western Cape region of South Africa (January-August 2021) found a reduced PCR amplification efficiency of the RdRp gene target of the Seegene, Allplex 2019-nCoV diagnostic assay when detecting the Delta variant. We propose that this can be used as a surrogate for variant detection.},
author = {Valley-Omar, Ziyaad and Marais, Gert and Iranzadeh, Arash and Naidoo, Michelle and Korsman, Stephen and Maponga, Tongai and Hussey, Hannah and Davies, Mary-Ann and Boulle, Andrew and Doolabh, Deelan and Laubscher, Mariska and Deetlefs, JD and Maritz, Jean and Scott, Lesley and Msomi, Nokukhanya and Tegally, Houriiyah and de Oliveira, Tulio and Bhiman, Jinal and Williamson, Carolyn and Preiser, Wolfgang and Hardie, Diana and Hsiao, Nei-yuan},
doi = {10.1101/2021.10.01.21264408},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Valley-Omar et al. - 2021 - Reduced amplification efficiency of the RNA-dependent-RNA-polymerase (RdRp) target enables tracking of the D.pdf:pdf},
journal = {medRxiv},
keywords = {OA,fund{\_}ack,original},
mendeley-tags = {OA,fund{\_}ack,original},
month = {oct},
pages = {2021.10.01.21264408},
publisher = {Cold Spring Harbor Laboratory Press},
title = {{Reduced amplification efficiency of the RNA-dependent-RNA-polymerase (RdRp) target enables tracking of the Delta SARS-CoV-2 variant using routine diagnostic tests}},
url = {https://www.medrxiv.org/content/10.1101/2021.10.01.21264408v1 https://www.medrxiv.org/content/10.1101/2021.10.01.21264408v1.abstract},
year = {2021}
}

Routine SARS-CoV-2 surveillance in the Western Cape region of South Africa (January-August 2021) found a reduced PCR amplification efficiency of the RdRp gene target of the Seegene, Allplex 2019-nCoV diagnostic assay when detecting the Delta variant. We propose that this can be used as a surrogate for variant detection.

@article{Hussey2021,
abstract = {A novel proxy for the Delta variant, RNA-dependent RNA polymerase target delay in the Seegene Allplex™ 2019-nCoV PCR assay, was associated with higher mortality (adjusted Odds Ratio 1.45 [95{\%}CI 1.13-1.86]), compared to presumptive Beta infection, in the Western Cape, South Africa (April-July 2021). Prior diagnosed infection and vaccination were protective. {\#}{\#}{\#} Competing Interest Statement The authors have declared no competing interest. {\#}{\#}{\#} Funding Statement This study was funded by the Grand Challenges ICODA pilot initiative delivered by Health Data Research UK and funded by the Bill {\&} Melinda Gates and the Minderoo Foundations (INV-017293), and by a research Flagship grant from the South African Medical Research Council (MRC-RFA-UFSP-01-2013/UKZN HIVEPI). Additional support was provided by the Francis Crick Institute which receives its core funding from Cancer Research UK (FC0010218), the UK Medical Research Council (FC0010218), and the Wellcome Trust (FC0010218) as well as Wellcome (203135, 222574). {\#}{\#}{\#} Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study was approved by the University of Cape Town Research Ethics Committee (HREC 460/2020). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors},
author = {Hussey, Hannah and Davies, Mary-Ann and Heekes, Alexa and Williamson, Carolyn and Valley-Omar, Ziyaad and Hardie, Diana and Korsman, Stephen and Doolabh, Deelan and Preiser, Wolfgang and Maponga, Tongai and Iranzadeh, Arash and Engelbrecht, Susan and Wasserman, Sean and Schrueder, Neshaad and Boloko, Linda and Symons, Greg and Raubenheimer, Peter and Viljoen, Abraham and Parker, Arifa and Cohen, Cheryl and Jassat, Waasila and Lessells, Richard and Wilkinson, Robert J and Boulle, Andrew and Hsiao, Nei-yuan},
doi = {10.1101/2021.10.23.21265412},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Hussey et al. - 2021 - Higher mortality associated with the SARS-CoV-2 Delta variant in the Western Cape, South Africa, using RdRp targe.pdf:pdf},
journal = {medRxiv},
keywords = {OA,fund{\_}ack,original},
mendeley-tags = {OA,fund{\_}ack,original},
month = {oct},
pages = {2021.10.23.21265412},
publisher = {Cold Spring Harbor Laboratory Press},
title = {{Higher mortality associated with the SARS-CoV-2 Delta variant in the Western Cape, South Africa, using RdRp target delay as a proxy}},
url = {https://www.medrxiv.org/content/10.1101/2021.10.23.21265412v1 https://www.medrxiv.org/content/10.1101/2021.10.23.21265412v1.abstract},
volume = {13},
year = {2021}
}

A novel proxy for the Delta variant, RNA-dependent RNA polymerase target delay in the Seegene Allplex™ 2019-nCoV PCR assay, was associated with higher mortality (adjusted Odds Ratio 1.45 [95%CI 1.13-1.86]), compared to presumptive Beta infection, in the Western Cape, South Africa (April-July 2021). Prior diagnosed infection and vaccination were protective. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study was funded by the Grand Challenges ICODA pilot initiative delivered by Health Data Research UK and funded by the Bill & Melinda Gates and the Minderoo Foundations (INV-017293), and by a research Flagship grant from the South African Medical Research Council (MRC-RFA-UFSP-01-2013/UKZN HIVEPI). Additional support was provided by the Francis Crick Institute which receives its core funding from Cancer Research UK (FC0010218), the UK Medical Research Council (FC0010218), and the Wellcome Trust (FC0010218) as well as Wellcome (203135, 222574). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study was approved by the University of Cape Town Research Ethics Committee (HREC 460/2020). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors