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Coronavirus variants of concern arise from long-term COVID infections in people who may be immune comprised and unable to clear the virus, a new study suggests. Frontiers in Virology published the findings by scientists at Emory University and the University of Oxford.

These results challenge traditional theories of how the virus might be evolving.

“Rather than evolving from transmission chains of acute COVID infections in hundreds of millions of people, our results show that the variants of concern come from rare cases when someone may have an active infection for months,” says Daniel Weissman, a corresponding author and Emory professor of biology and physics.

The researchers built a theoretical model using existing data and novel software. The model rules out the theory that the VOCs emerged from sustained transmission of acute infections, instead it supports the idea that each variant evolved within a single individual with a chronic infection.

Their model shows that multiple mutations occurred, each of which may have been either neutral or slightly advantageous to viral fitness. In this way, a variant eventually acquired a set of mutations allowing it to become more transmissible.

“A key take-home message is that it is important to find these individuals who are chronically infected and provide support for them to recover,” adds Mahan Ghafari, first author of the paper and a postdoctoral researcher at the University of Oxford. “In many cases they may be asymptomatic and not even realize that they are infected with COVID although they are actively shedding the virus.”

“Who knows what variant could be boiling up next from a chronically infected individual?” Ghafari says. “Our study shows that from an evolutionary point of view, we can expect something completely different from the previous VOCs. If we want to stay a step ahead of this virus, we need to be more actively identifying and surveilling people with chronic infections.”

The Importance of Variants of Concern

Viruses like SARS-CoV-2 continuously evolve due to mutations in the genetic code that may occur when they replicate. “When a virus copies itself, it doesn’t always make perfect copies,” Weissman explains. Occasionally the mutations result in a variant of the virus that may make it more transmissible, more difficult to detect and treat, and even more lethal.

The World Health Organization (WHO) defines a SARS-CoV-2 variant of concern as one that is more likely to cause infections even in those who are vaccinated or in those who were previously infected.

“During the first few months of the pandemic, it didn’t look like the coronavirus was going to adapt into a variant of concern [VOC],” Weissman says. “But then, boom, boom, boom! Not only did the coronavirus evolve into VOCs, it did it three times in quick succession in late 2020.”

WHO dubbed these first three variants of concern alpha, beta, and gamma. A big question was why each of these VOCs emerged at roughly the same time and apparently in three far-flung areas of the world. Another mystery was why large clusters of mutations occurred in the VOCs.

VOCs have thus become a major focus for pandemic control.

At least some of the mutations had been detected in chronic cases of COVID, leading to the hypothesis that these long-term cases may be the source of the VOCs rather than from sustained transmission of acute infections in areas of the world with poor genomic surveillance of the virus.

Ghafari, Weissman, and their collaborators were among the first teams to methodically test these theories surrounding the emergence of the alpha, beta and gamma VOCs.

“Ideally, we’d like to eventually be able to quantify the timing at which new variants might emerge in the future,” Weissman says. “That has huge implications from a public health perspective.

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