Prevalence of persistent SARS-CoV-2 in a large community surveillance study

Mahan Ghafari*, Matthew Hall, Tanya Golubchik, Daniel Ayoubkhani, Thomas House, George MacIntyre-Cockett, Helen R. Fryer, Laura Thomson, Anel Nurtay, Steven A. Kemp, Luca Ferretti, David Buck, Angie Green, Amy Trebes, Lorne J. Lonie, Paolo Piazza, Ruth Studley, Emma Rourke, Darren L. Smith, Matthew BashtonAndrew Nelson, Matthew Crown, Clare McCann, Gregory R. Young, Rui Andre Nunes dos Santos, Zack Richards, Mohammad Adnan Tariq, Roberto Cahuantzi, Wellcome Sanger Institute COVID-19 Surveillance Team, COVID-19 Infection Survey Group, The COVID-19 Genomics UK (COG-UK) Consortium, Jeff Barrett, Christophe Fraser, David Bonsall, Ann Sarah Walker, Katrina Lythgoe*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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Abstract

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.

Original languageEnglish
Pages (from-to)1094-1101
Number of pages25
JournalNature
Volume626
Issue number8001
Early online date21 Feb 2024
DOIs
Publication statusPublished - 29 Feb 2024

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