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

• 成果类型: Article
• 署名作者: Ghafari, Mahan; Hall, Matthew; Golubchik, Tanya; Ayoubkhani, Daniel; House, Thomas; MacIntyre-Cockett, George; Fryer, Helen R.; Thomson, Laura; Nurtay, Anel; Kemp, Steven A.; Ferretti, Luca; Buck, David; Green, Angie; Trebes, Amy; Piazza, Paolo; Lonie, Lorne J.; Studley, Ruth; Rourke, Emma; Smith, Darren L.; Bashton, Matthew; Nelson, Andrew; Crown, Matthew; McCann, Clare; Young, Gregory R.; dos Santos, Rui Andre Nunes; Richards, Zack; Tariq, Mohammad Adnan; Cahuantzi, Roberto; Barrett, Jeff; Fraser, Christophe; Bonsall, David; Walker, Ann Sarah; Lythgoe, Katrina
• 署名单位: University of Oxford; University of Oxford; University of Oxford; University of Sydney; University of Leicester; University of Manchester; University of Oxford; Wellcome Centre for Human Genetics; Northumbria University; Northumbria University; Wellcome Trust Sanger Institute; Oxford University Hospitals NHS Foundation Trust; University of Oxford; University of Oxford; University of Oxford; University of Oxford; University of London; University College London; Medical Research Council Clinical Trials Unit
• 刊物名称: Nature
• ISSN/ISSBN: 0028-6991
• DOI: 10.1038/s41586-024-07029-4
• 发表日期: 2024-02-29
• 页码: 1094-+
• 关键词: infection

摘要

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.