British researchers have found that a higher percentage of the population than initially assumed has had “persistent” Covid-19 infections lasting more than 30 days, with one to three of every 100 infections likely to last a month or longer.
The Oxford University team, using data from the Office for National Statistics Covid Infection Survey (ONS-CIS), found 381 people with the same viral infection for a month or longer – including 54 whose persistent infection lasted two months and two over six months – out of 77 561 infections detected through ONS-CIS between November 2020 and August 2022.
In some cases, the infecting lineage had gone extinct in the general population, reports Health Policy Watch.
More than 90 000 ONS-CIS participants were sampled monthly for almost three years.
“As the ONS-CIS is a community-based surveillance study, our observations suggest that the pool of people in which long-term infections could occur, and hence potential sources of divergent variants, may be much larger than generally thought,” wrote the study authors.
Their research appears to debunk an assumption that new variants are only formed because of prolonged Covid-19 infections in immunocompromised individuals.
The results show that the prevalence of persistent infections in the general population may be much higher and, therefore, also play a role in the evolution of the virus.
Persistence and long Covid
Their study, published in Nature, also found that people with persistent infections lasting for 30 days or longer were 55% more likely to have long Covid than those with more typical infections.
“Although the link may not be causal, the results suggest persistent infections could contribute to the pathophysiology of long Covid,” said co-lead author Dr Katrina Lythgoe of Oxford’s Department of Biology and its Pandemic Sciences Institute.
The paper said that not every persistent infection can lead to long-term Covid-19, and not all cases of long-term Covid are due to persistent infection.
Nonetheless, the results suggest to persistent infections could be contributing to the pathophysiology of long Covid, the authors said.
Co-lead author Dr Mahan Ghafari of Oxford’s Pandemic Sciences Institute in its Nuffield Department of Medicine, cautioned that the data from ONS-CIS did not include details about the medical history of people with persistent infections, so it was unknown how many of them were immunocompromised.
The scientists also found rare infections with the same variant. They identified only 60 reinfections by the same major lineage, suggesting infection builds at least some immunity in infected people from the same variant.
Study details
Prevalence of persistent SARS-CoV-2 in a large community surveillance study
Mahan Ghafari, Matthew Hall, Katrina Lythgoe, et al.
Published in Nature on 21 February 2024
Abstract
Persistent SARS-CoV-2 infections may act as viral reservoirs that could seed future outbreaks, give rise to highly divergent lineages and contribute to cases with post-acute Covid-19 sequelae (long Covid). 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 people11,12,13,14. This work has profound implications for understanding and characterising SARS-CoV-2 infection, epidemiology and evolution.
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