@article{Tomasicchio2024,
abstract = {Rationale: In the upper respiratory tract replicating (culturable) SARS-CoV-2 is recoverable for {\~{}} 4 to 8 days after symptom onset, however, there is paucity of data about the frequency or duration of replicating virus in the lower respiratory tract (i.e. the human lung). Objectives: We undertook lung tissue sampling (needle biopsy), shortly after death, in 42 mechanically ventilated decedents during the Beta and Delta waves. An independent group of 18 ambulatory patents served as a control group. Methods: Lung biopsy cores from decedents underwent viral culture, histopathological analysis, electron microscopy, transcriptomic profiling and immunohistochemistry. Results: 38{\%} (16/42) of mechanically ventilated decedents had culturable virus in the lung for a median of 15 days (persisting for up to 4 weeks) after symptom onset. Lung viral culture positivity was not associated with comorbidities or steroid use. Delta but not Beta variant lung culture positivity was associated with accelerated death and secondary bacterial infection (p{\textless}0.05). Nasopharyngeal culture was negative in 23.1{\%} (6/26) of decedents despite lung culture positivity. This, hitherto, undescribed bio-phenotype of lung-specific persisting viral replication was associated with an enhanced transcriptomic pulmonary pro-inflammatory response but with concurrent viral culture positivity. Conclusions: Concurrent, rather than sequential active viral replication continues to drive a heightened pro-inflammatory response in the human lung beyond the second week of illness and was associated with variant-specific increased mortality and morbidity. These findings have potential implications for the design of interventional strategies and clinical management of patients with severe COVID-19 disease.},
author = {Tomasicchio, Michele and Jaumdally, Shameem and Wilson, Lindsay and Kotze, Andrea and Semple, Lynn and Meier, Stuart and Pooran, Anil and Esmail, Aliasgar and Pillay, Komala and Roberts, Riyaadh and Kriel, Raymond and Meldau, Richard and Oelofse, Suzette and Mandviwala, Carley and Burns, Jessica and Londt, Rolanda and Davids, Malika and van der Merwe, Charnay and Roomaney, Aqeedah and K{\"{u}}hn, Loui{\'{e}} and Perumal, Tahlia and Scott, Alex J and Hale, Martin J and Baillie, Vicky and Mahtab, Sana and Williamson, Carolyn and Joseph, Rageema and Sigal, Alex and Joubert, Ivan and Piercy, Jenna and Thomson, David and Fredericks, David L and Miller, Malcolm G A and Nunes, Marta C and Madhi, Shabir A and Dheda, Keertan},
doi = {10.1164/RCCM.202308-1438OC},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Tomasicchio et al. - 2024 - SARS-CoV-2 viral replication persists in the human lung for several weeks after symptom onset.pdf:pdf},
issn = {1073-449X},
journal = {American Journal of Respiratory and Critical Care Medicine},
keywords = {COVID-19,OA,SARS-CoV-2,fund{\_}ack,lower respiratory tract,mechanically ventilated patients,original,virus replication},
mendeley-tags = {OA,fund{\_}ack,original},
month = {jan},
pages = {rccm.202308--1438OC},
pmid = {38226855},
publisher = {AJRCCM Articles in Press. Published},
title = {{SARS-CoV-2 viral replication persists in the human lung for several weeks after symptom onset}},
url = {https://www.atsjournals.org/doi/10.1164/rccm.202308-1438OC},
year = {2024}
}

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A","Dheda, K."],"bibdata":{"bibtype":"article","type":"article","abstract":"Rationale: In the upper respiratory tract replicating (culturable) SARS-CoV-2 is recoverable for \\  4 to 8 days after symptom onset, however, there is paucity of data about the frequency or duration of replicating virus in the lower respiratory tract (i.e. the human lung). Objectives: We undertook lung tissue sampling (needle biopsy), shortly after death, in 42 mechanically ventilated decedents during the Beta and Delta waves. An independent group of 18 ambulatory patents served as a control group. Methods: Lung biopsy cores from decedents underwent viral culture, histopathological analysis, electron microscopy, transcriptomic profiling and immunohistochemistry. Results: 38% (16/42) of mechanically ventilated decedents had culturable virus in the lung for a median of 15 days (persisting for up to 4 weeks) after symptom onset. Lung viral culture positivity was not associated with comorbidities or steroid use. Delta but not Beta variant lung culture positivity was associated with accelerated death and secondary bacterial infection (p\\textless0.05). Nasopharyngeal culture was negative in 23.1% (6/26) of decedents despite lung culture positivity. This, hitherto, undescribed bio-phenotype of lung-specific persisting viral replication was associated with an enhanced transcriptomic pulmonary pro-inflammatory response but with concurrent viral culture positivity. Conclusions: Concurrent, rather than sequential active viral replication continues to drive a heightened pro-inflammatory response in the human lung beyond the second week of illness and was associated with variant-specific increased mortality and morbidity. These findings have potential implications for the design of interventional strategies and clinical management of patients with severe COVID-19 disease.","author":[{"propositions":[],"lastnames":["Tomasicchio"],"firstnames":["Michele"],"suffixes":[]},{"propositions":[],"lastnames":["Jaumdally"],"firstnames":["Shameem"],"suffixes":[]},{"propositions":[],"lastnames":["Wilson"],"firstnames":["Lindsay"],"suffixes":[]},{"propositions":[],"lastnames":["Kotze"],"firstnames":["Andrea"],"suffixes":[]},{"propositions":[],"lastnames":["Semple"],"firstnames":["Lynn"],"suffixes":[]},{"propositions":[],"lastnames":["Meier"],"firstnames":["Stuart"],"suffixes":[]},{"propositions":[],"lastnames":["Pooran"],"firstnames":["Anil"],"suffixes":[]},{"propositions":[],"lastnames":["Esmail"],"firstnames":["Aliasgar"],"suffixes":[]},{"propositions":[],"lastnames":["Pillay"],"firstnames":["Komala"],"suffixes":[]},{"propositions":[],"lastnames":["Roberts"],"firstnames":["Riyaadh"],"suffixes":[]},{"propositions":[],"lastnames":["Kriel"],"firstnames":["Raymond"],"suffixes":[]},{"propositions":[],"lastnames":["Meldau"],"firstnames":["Richard"],"suffixes":[]},{"propositions":[],"lastnames":["Oelofse"],"firstnames":["Suzette"],"suffixes":[]},{"propositions":[],"lastnames":["Mandviwala"],"firstnames":["Carley"],"suffixes":[]},{"propositions":[],"lastnames":["Burns"],"firstnames":["Jessica"],"suffixes":[]},{"propositions":[],"lastnames":["Londt"],"firstnames":["Rolanda"],"suffixes":[]},{"propositions":[],"lastnames":["Davids"],"firstnames":["Malika"],"suffixes":[]},{"propositions":["van","der"],"lastnames":["Merwe"],"firstnames":["Charnay"],"suffixes":[]},{"propositions":[],"lastnames":["Roomaney"],"firstnames":["Aqeedah"],"suffixes":[]},{"propositions":[],"lastnames":["Kühn"],"firstnames":["Louié"],"suffixes":[]},{"propositions":[],"lastnames":["Perumal"],"firstnames":["Tahlia"],"suffixes":[]},{"propositions":[],"lastnames":["Scott"],"firstnames":["Alex","J"],"suffixes":[]},{"propositions":[],"lastnames":["Hale"],"firstnames":["Martin","J"],"suffixes":[]},{"propositions":[],"lastnames":["Baillie"],"firstnames":["Vicky"],"suffixes":[]},{"propositions":[],"lastnames":["Mahtab"],"firstnames":["Sana"],"suffixes":[]},{"propositions":[],"lastnames":["Williamson"],"firstnames":["Carolyn"],"suffixes":[]},{"propositions":[],"lastnames":["Joseph"],"firstnames":["Rageema"],"suffixes":[]},{"propositions":[],"lastnames":["Sigal"],"firstnames":["Alex"],"suffixes":[]},{"propositions":[],"lastnames":["Joubert"],"firstnames":["Ivan"],"suffixes":[]},{"propositions":[],"lastnames":["Piercy"],"firstnames":["Jenna"],"suffixes":[]},{"propositions":[],"lastnames":["Thomson"],"firstnames":["David"],"suffixes":[]},{"propositions":[],"lastnames":["Fredericks"],"firstnames":["David","L"],"suffixes":[]},{"propositions":[],"lastnames":["Miller"],"firstnames":["Malcolm","G","A"],"suffixes":[]},{"propositions":[],"lastnames":["Nunes"],"firstnames":["Marta","C"],"suffixes":[]},{"propositions":[],"lastnames":["Madhi"],"firstnames":["Shabir","A"],"suffixes":[]},{"propositions":[],"lastnames":["Dheda"],"firstnames":["Keertan"],"suffixes":[]}],"doi":"10.1164/RCCM.202308-1438OC","file":":C$\\$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Tomasicchio et al. - 2024 - SARS-CoV-2 viral replication persists in the human lung for several weeks after symptom onset.pdf:pdf","issn":"1073-449X","journal":"American Journal of Respiratory and Critical Care Medicine","keywords":"COVID-19,OA,SARS-CoV-2,fund_ack,lower respiratory tract,mechanically ventilated patients,original,virus replication","mendeley-tags":"OA,fund_ack,original","month":"jan","pages":"rccm.202308–1438OC","pmid":"38226855","publisher":"AJRCCM Articles in Press. 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