Study finds high number of persistent COVID-19 infections in general population

A new study led by the University of Oxford has found that a high proportion of SARS-CoV-2 infections in the general population result in persistent infections lasting a month or more. The results were published in the journal Nature.

It has long been thought that prolonged COVID-19 infections in immunocompromised people may have caused the multiple new variants that emerged during the coronavirus pandemic and seeded successive waves of infection, including the alpha and omicron variants. . But until now, the prevalence of persistent COVID-19 infections in the general population and how the virus evolves in these situations remained unknown.

To investigate this, researchers used data from the Office for National Statistics COVID Infection Survey (ONS-CIS), which tested participants approximately once a month.

Of the more than 90,000 participants, 3,603 provided two or more positive samples between November 2020 and August 2022, where the virus was sequenced. Of these, 381 people tested positive for the same viral infection over a period of a month or more.

Within this group, 54 people had persistent infection lasting at least two months. Researchers estimate that between one in a thousand and one in 200 infections (0.1 to 0.5%) can become persistent and last at least 60 days.

In some cases, individuals remained infected with virus variants that had disappeared from the general population. In contrast, the researchers found that reinfection with the same variant was very rare, likely due to the host developing immunity to that variant and the frequency of the variant decreasing to very low levels after a few months.

Of the 381 persistent infections, 65 underwent at least three PCR tests during their infection. Most (82%) of these individuals demonstrated rebounding viral dynamics, experiencing high, then low, then high viral load dynamics. According to the researchers, this demonstrates that the virus can retain its ability to actively replicate during prolonged infections.

In the study, people with persistent infections were 55% more likely to report having long-lasting COVID-19 symptoms more than 12 weeks after infection began than people with more typical infections.

Some individuals have had extremely high numbers of mutations, including mutations that define new variants of the coronavirus, change the target sites of monoclonal antibodies, and introduce changes to the coronavirus spike protein. However, most individuals did not have large numbers of mutations, suggesting that not all persistent infections will be a potential source of new variants of concern.

Co-lead author of the study, Dr Mahan Ghafari (Institute of Pandemic Sciences, Nuffield Department of Medicine, University of Oxford), said: “Our observations highlight the continued importance of community genomic surveillance both to monitor the emergence and spread of new variants, but also to gain a fundamental understanding of the natural history and evolution of new pathogens and their clinical implications for patients.

Dr Katrina Lythgoe (Department of Biology and Institute of Pandemic Science, University of Oxford) said: “Although the link between viral persistence and long COVID cannot be causal, these results suggest that persistent infections could contribute to the pathophysiology of long COVID. Indeed, many other possible mechanisms have been suggested to contribute to long COVID, including inflammation, organ damage, and microthrombosis.