A much higher percentage of the population has experienced “persistent” COVID-19 infections lasting more than 30 days than initially assumed, according to new research by the University of Oxford.

The study, published on February 21 in Nature, found that one to three of every 100 infections may last a month or longer.

The scientists, using data from the Office for National Statistics COVID Infection Survey (ONS-CIS), found 381 individuals 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. More than 90,000 ONS-CIS participants were sampled monthly for almost three years.

What “we uncovered is striking, given the leading hypothesis that many of the variants of concern emerged wholly or partially during long-term chronic infections in immunocompromised individuals,” the authors wrote in their paper. “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.”

In other words, the study debunks an assumption that new variants are only formed because of prolonged COVID-19 infections in immunocompromised individuals. This new study shows that the prevalence of persistent COVID-19 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

Relatedly, the authors found that people with persistent infections lasting for 30 days or longer were 55% more likely to report having long COVID than people with more typical infections.

“Although the link between viral persistence and Long COVID may not be causal, these 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 carefully points out that not every persistent infection can lead to long-term COVID-19, and not all cases of long-term COVID-19 are due to persistent infection. “Indeed,” said Lythgoe, “many other possible mechanisms have been suggested to contribute to Long COVID, including inflammation, organ damage, and micro thrombosis.”

Nonetheless, “these results suggest that persistent infections could be contributing to the pathophysiology of long COVID,” the paper reads.

Mutation Rates

What about the rate of mutation?

Some people who developed persistent infections had many mutations, suggesting they could act as reservoirs to seed new variants of concern. However, this was only sometimes the case.

“Certain individuals showed an extremely high number of mutations, including mutations that define new coronavirus variants, alter target sites for monoclonal antibodies, and introduce changes to the coronavirus spike protein,” the authors wrote. “However, most individuals did not harbour a large number of mutations, suggesting that not every persistent infection will be a potential source for new concerning variants.”

However, 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, such as with cancer, advanced HIV, etc.

He said the hope is that there would be further studies to better understand these individuals who developed persistent COVID and their health implications, and also to better understand how likely it is for these persistent infections to transmit highly mutated variants to the rest of the population.

Variant Reinfections

Finally, the scientists also found rare infections with the same variant. They identified only 60 reinfections by the same major lineage, suggesting that infection does build at least some immunity in infected individuals from the same variant.

“Our observations highlight the continuing importance of community-based 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 novel pathogens and their clinical implications for patients,” Ghafari said.

Image Credits: peterschreiber.media/Shutterstock , Flickr – NIAID, Flickr.