TY - JOUR
T1 - Prevalence of persistent SARS-CoV-2 in a large community surveillance study
AU - Ghafari, Mahan
AU - Hall, Matthew
AU - Golubchik, Tanya
AU - Ayoubkhani, Daniel
AU - House, Thomas
AU - MacIntyre-Cockett, George
AU - Fryer, Helen R.
AU - Thomson, Laura
AU - Nurtay, Anel
AU - Kemp, Steven A.
AU - Ferretti, Luca
AU - Buck, David
AU - Green, Angie
AU - Trebes, Amy
AU - Lonie, Lorne J.
AU - Piazza, Paolo
AU - Studley, Ruth
AU - Rourke, Emma
AU - Smith, Darren L.
AU - Bashton, Matthew
AU - Nelson, Andrew
AU - Crown, Matthew
AU - McCann, Clare
AU - Young, Gregory R.
AU - Santos, Rui Andre Nunes dos
AU - Richards, Zack
AU - Tariq, Mohammad Adnan
AU - Cahuantzi, Roberto
AU - Wellcome Sanger Institute COVID-19 Surveillance Team
AU - COVID-19 Infection Survey Group
AU - The COVID-19 Genomics UK (COG-UK) Consortium
AU - Barrett, Jeff
AU - Fraser, Christophe
AU - Bonsall, David
AU - Walker, Ann Sarah
AU - Lythgoe, Katrina
N1 - Funding information: The CIS was funded by the Department of Health and Social Care and the UK Health Security Agency, with in-kind support from the Welsh Government, the Department of Health on behalf of the Northern Ireland Government and the Scottish Government. The COVID-19 Infection Survey Group of the COVID-19 Genomics UK (COG-UK) Consortium was supported by funding from the Medical Research Council part of UK Research & Innovation, the National Institute of Health Research (NIHR) (grant code: MC_PC_19027) and Genome Research Limited, operating as the Wellcome Sanger Institute. We acknowledge use of data generated through the COVID-19 Genomics Programme funded by the Department of Health and Social Care. A.S.W. is supported by the NIHR Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance at the University of Oxford in partnership with the UK Health Security Agency (NIHR200915) and the NIHR Oxford Biomedical Research Centre, and is an NIHR Senior Investigator. T.H. is supported by the Royal Society and Alan Turing Institute for Data Science and Artificial Intelligence. K.L. is supported by the Royal Society and the Wellcome Trust (107652/Z/15/Z) and by the Li Ka Shing Foundation. The research was supported by the Wellcome Trust Core Award grant number 203141/Z/16/Z, with funding from the NIHR Oxford BRC.
PY - 2024/2/29
Y1 - 2024/2/29
N2 - Persistent SARS-CoV-2 infections may act as viral reservoirs that could seed future outbreaks
1-5, give rise to highly divergent lineages
6-8 and contribute to cases with post-acute COVID-19 sequelae (long COVID)
9,10. However, the population prevalence of persistent infections, their viral load kinetics and evolutionary dynamics over the course of infections remain largely unknown. Here, using viral sequence data collected as part of a national infection survey, we identified 381 individuals with SARS-CoV-2 RNA at high titre persisting for at least 30 days, of which 54 had viral RNA persisting at least 60 days. We refer to these as 'persistent infections' as available evidence suggests that they represent ongoing viral replication, although the persistence of non-replicating RNA cannot be ruled out in all. Individuals with persistent infection had more than 50% higher odds of self-reporting long COVID than individuals with non-persistent infection. We estimate that 0.1-0.5% of infections may become persistent with typically rebounding high viral loads and last for at least 60 days. In some individuals, we identified many viral amino acid substitutions, indicating periods of strong positive selection, whereas others had no consensus change in the sequences for prolonged periods, consistent with weak selection. Substitutions included mutations that are lineage defining for SARS-CoV-2 variants, at target sites for monoclonal antibodies and/or are commonly found in immunocompromised people
11-14. This work has profound implications for understanding and characterizing SARS-CoV-2 infection, epidemiology and evolution.
AB - Persistent SARS-CoV-2 infections may act as viral reservoirs that could seed future outbreaks
1-5, give rise to highly divergent lineages
6-8 and contribute to cases with post-acute COVID-19 sequelae (long COVID)
9,10. However, the population prevalence of persistent infections, their viral load kinetics and evolutionary dynamics over the course of infections remain largely unknown. Here, using viral sequence data collected as part of a national infection survey, we identified 381 individuals with SARS-CoV-2 RNA at high titre persisting for at least 30 days, of which 54 had viral RNA persisting at least 60 days. We refer to these as 'persistent infections' as available evidence suggests that they represent ongoing viral replication, although the persistence of non-replicating RNA cannot be ruled out in all. Individuals with persistent infection had more than 50% higher odds of self-reporting long COVID than individuals with non-persistent infection. We estimate that 0.1-0.5% of infections may become persistent with typically rebounding high viral loads and last for at least 60 days. In some individuals, we identified many viral amino acid substitutions, indicating periods of strong positive selection, whereas others had no consensus change in the sequences for prolonged periods, consistent with weak selection. Substitutions included mutations that are lineage defining for SARS-CoV-2 variants, at target sites for monoclonal antibodies and/or are commonly found in immunocompromised people
11-14. This work has profound implications for understanding and characterizing SARS-CoV-2 infection, epidemiology and evolution.
KW - Amino Acid Substitution
KW - Antibodies, Monoclonal/immunology
KW - COVID-19/epidemiology
KW - Evolution, Molecular
KW - Health Surveys
KW - Humans
KW - Immunocompromised Host/immunology
KW - Mutation
KW - Persistent Infection/epidemiology
KW - Post-Acute COVID-19 Syndrome/epidemiology
KW - Prevalence
KW - RNA, Viral/analysis
KW - SARS-CoV-2/chemistry
KW - Selection, Genetic
KW - Self Report
KW - Time Factors
KW - Viral Load
KW - Virus Replication
UR - http://www.scopus.com/inward/record.url?scp=85185463403&partnerID=8YFLogxK
U2 - 10.1038/s41586-024-07029-4
DO - 10.1038/s41586-024-07029-4
M3 - Article
C2 - 38383783
SN - 0028-0836
VL - 626
SP - 1094
EP - 1101
JO - Nature
JF - Nature
IS - 8001
ER -