@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}
}

{"_id":"7yyd2Xv9LmFLqarFd","bibbaseid":"benede-tincho-walters-subbiah-ngomti-baguma-butters-mennen-etal-distincttcellfunctionalprofilesinsarscov2seropositiveandseronegativechildrenassociatedwithendemichumancoronaviruscrossreactivity-2023","author_short":["Benede, N. S.","Tincho, M. B","Walters, A.","Subbiah, V.","Ngomti, A.","Baguma, R.","Butters, C.","Mennen, M.","Skelem, S.","Adriaanse, M.","van Graan, S.","Balla, S. R.","Moyo-Gwete, T.","Moore, P. L.","Botha, M.","Workman, L.","Zar, H. J.","Ntusi, N. A. B.","Zühlke, L.","Webb, K.","Riou, C.","Burgers, W. A","Keeton, R. S"],"bibdata":{"bibtype":"article","type":"article","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":[{"propositions":[],"lastnames":["Benede"],"firstnames":["Ntombi","S.B."],"suffixes":[]},{"propositions":[],"lastnames":["Tincho"],"firstnames":["Marius","B"],"suffixes":[]},{"propositions":[],"lastnames":["Walters"],"firstnames":["Avril"],"suffixes":[]},{"propositions":[],"lastnames":["Subbiah"],"firstnames":["Vennesa"],"suffixes":[]},{"propositions":[],"lastnames":["Ngomti"],"firstnames":["Amkele"],"suffixes":[]},{"propositions":[],"lastnames":["Baguma"],"firstnames":["Richard"],"suffixes":[]},{"propositions":[],"lastnames":["Butters"],"firstnames":["Claire"],"suffixes":[]},{"propositions":[],"lastnames":["Mennen"],"firstnames":["Mathilda"],"suffixes":[]},{"propositions":[],"lastnames":["Skelem"],"firstnames":["Sango"],"suffixes":[]},{"propositions":[],"lastnames":["Adriaanse"],"firstnames":["Marguerite"],"suffixes":[]},{"propositions":["van"],"lastnames":["Graan"],"firstnames":["Strauss"],"suffixes":[]},{"propositions":[],"lastnames":["Balla"],"firstnames":["Sashkia","R."],"suffixes":[]},{"propositions":[],"lastnames":["Moyo-Gwete"],"firstnames":["Thandeka"],"suffixes":[]},{"propositions":[],"lastnames":["Moore"],"firstnames":["Penny","L."],"suffixes":[]},{"propositions":[],"lastnames":["Botha"],"firstnames":["Maresa"],"suffixes":[]},{"propositions":[],"lastnames":["Workman"],"firstnames":["Lesley"],"suffixes":[]},{"propositions":[],"lastnames":["Zar"],"firstnames":["Heather","J."],"suffixes":[]},{"propositions":[],"lastnames":["Ntusi"],"firstnames":["Ntobeko","A.","B."],"suffixes":[]},{"propositions":[],"lastnames":["Zühlke"],"firstnames":["Liesl"],"suffixes":[]},{"propositions":[],"lastnames":["Webb"],"firstnames":["Kate"],"suffixes":[]},{"propositions":[],"lastnames":["Riou"],"firstnames":["Catherine"],"suffixes":[]},{"propositions":[],"lastnames":["Burgers"],"firstnames":["Wendy","A"],"suffixes":[]},{"propositions":[],"lastnames":["Keeton"],"firstnames":["Roanne","S"],"suffixes":[]}],"doi":"10.1101/2023.05.16.23290059","file":":C$\\$:/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","bibtex":"@article{Benede2023,\r\nabstract = {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},\r\nauthor = {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},\r\ndoi = {10.1101/2023.05.16.23290059},\r\nfile = {: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},\r\njournal = {medRxiv},\r\nkeywords = {OA,fund{\\_}ack,genomics{\\_}fund{\\_}ack,original},\r\nmendeley-tags = {OA,fund{\\_}ack,genomics{\\_}fund{\\_}ack,original},\r\nmonth = {may},\r\npages = {2023.05.16.23290059},\r\npublisher = {Cold Spring Harbor Laboratory Press},\r\ntitle = {{Distinct T cell functional profiles in SARS-CoV-2 seropositive and seronegative children associated with endemic human coronavirus cross-reactivity}},\r\nurl = {https://www.medrxiv.org/content/10.1101/2023.05.16.23290059v1 https://www.medrxiv.org/content/10.1101/2023.05.16.23290059v1.abstract},\r\nyear = {2023}\r\n}\r\n","author_short":["Benede, N. S.","Tincho, M. B","Walters, A.","Subbiah, V.","Ngomti, A.","Baguma, R.","Butters, C.","Mennen, M.","Skelem, S.","Adriaanse, M.","van Graan, S.","Balla, S. R.","Moyo-Gwete, T.","Moore, P. L.","Botha, M.","Workman, L.","Zar, H. J.","Ntusi, N. A. B.","Zühlke, L.","Webb, K.","Riou, C.","Burgers, W. A","Keeton, R. S"],"key":"Benede2023","id":"Benede2023","bibbaseid":"benede-tincho-walters-subbiah-ngomti-baguma-butters-mennen-etal-distincttcellfunctionalprofilesinsarscov2seropositiveandseronegativechildrenassociatedwithendemichumancoronaviruscrossreactivity-2023","role":"author","urls":{"Paper":"https://www.medrxiv.org/content/10.1101/2023.05.16.23290059v1 https://www.medrxiv.org/content/10.1101/2023.05.16.23290059v1.abstract"},"keyword":["OA","fund_ack","genomics_fund_ack","original"],"metadata":{"authorlinks":{}}},"bibtype":"article","biburl":"https://drive.google.com/uc?export=download&id=1-YbiDDZeTcX0VKKZlqqSKulhgmeoOpLm","dataSources":["Krmt6gt9ktB2s6ARh","y6ojaHcuarkmc4yRQ"],"keywords":["oa","fund_ack","genomics_fund_ack","original"],"search_terms":["distinct","cell","functional","profiles","sars","cov","seropositive","seronegative","children","associated","endemic","human","coronavirus","cross","reactivity","benede","tincho","walters","subbiah","ngomti","baguma","butters","mennen","skelem","adriaanse","van graan","balla","moyo-gwete","moore","botha","workman","zar","ntusi","zühlke","webb","riou","burgers","keeton"],"title":"Distinct T cell functional profiles in SARS-CoV-2 seropositive and seronegative children associated with endemic human coronavirus cross-reactivity","year":2023}