Vaccine-resistant coronavirus 'mutants' are more likely when transmission is high, new model finds

Vaccine-resistant coronavirus mutants are more likely to emerge when a large fraction of the population is vaccinated and viral transmission is high, and no steps are taken to stop the spread, a new model suggests. In other words, a situation that looks a lot like the current one in the U.S. 

The mathematical model, published July 30 in the journal Scientific Reports, simulates how the rate of vaccination and rate of viral transmission in a given population influence which SARS-CoV-2 variants come to dominate the viral landscape. The best way to snuff out vaccine-resistant mutants before they spread is to get shots in arms as quickly as possible, while also keeping viral transmission low, the authors found; in their model, they assume low transmission rates reflect the adoption of behavioral measures like masking and social distancing.

That last point is crucial: If viral transmission is low, any vaccine-resistant mutants that do emerge get fewer chances to spread, and thus, they're more likely to die out, said senior author Fyodor Kondrashov, who runs an evolutionary genomics lab at the Institute of Science and Technology Austria. 

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If viral transmission is high, vaccine-resistant mutants get the chance to infect many unvaccinated and vaccinated people. That means these variants could easily outcompete other versions of the virus and would soon emerge as the dominant strains in circulation.

This worst-case scenario occurs when many, but not all, people in the population are vaccinated, transmission rates are high and the virus is spreading unchecked, the authors found. In this scenario, vaccine-resistant mutants are most likely to emerge when about 60% of the population is vaccinated; at that point, a large proportion of the population is protected against the original virus, so infections from that virus strain begin to wane and vaccine-resistant mutants gain a competitive edge. And if viral transmission remains high, those mutants will soon reign supreme, the model suggests.

These results are "not counterintuitive, nor surprising," said Michael Levy, an associate professor of epidemiology in the departments of biostatistics and epidemiology at the University of Pennsylvania's Perelman School of Medicine, who was not involved in the study. 

"Evolution needs pressure, and as more people are vaccinated, there is more selective pressure on the virus" to change in order to evade vaccine-induced immune responses, Levy told Live Science in an email. Though not necessarily surprising, the new study calls attention to the "very real possibility" that emerging mutants may challenge the effectiveness of existing vaccines.

Dr. Anthony Fauci, head of the National Institute of Allergy and Infectious Diseases, expressed similar concerns when discussing the widespread delta variant with the news agency McClatchy this week. Early data suggest that vaccines still protect against the delta variant, although they work better against the original virus, Live Science previously reported. But Fauci said that he fears that, given current infection rates, the virus now has "ample chance" to generate an even more formidable mutant than delta. 

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"There could be a variant that's lingering out there that can push aside delta," Fauci said. Reducing viral transmission would help stamp out such a variant before it takes over, or prevent it from ever existing. 

The new model underscores the risk of letting SARS-CoV-2 spread unabated, particularly when a large fraction of people — but not everyone — is vaccinated. That said, the model doesn't perfectly match reality, and we're still contending with big unknowns, Kondrashov said. 

For instance, in the simplified model, the original and mutant strains are all equally transmissible, but different strains often vary in transmissibility. For instance, the delta variant, thought to be the most transmissible version of the virus to date, has so far outcompeted all the known coronavirus variants with some vaccine-evading traits. 

Being able to dodge vaccines helps a mutant take over only once a population nears herd immunity for other versions of the virus; before that point, vaccine-resistant variants must compete with vaccine-vulnerable variants for bodies to infect, Kondrashov said. Because delta spreads so easily, delta holds a competitive advantage over vaccine-resistant variants of lower transmissibility — for now. 

It's also not clear how many mutations a variant would need to pick up to be both highly transmissible and able to evade vaccines, or if that is likely with SARS-CoV-2; a mutant like that would be concerning, if it could start spreading while delta is surging.   

Highly transmissible strains may increase the rate at which new vaccine-resistant mutants emerge, since the high rate of spread gives the virus more chances to mutate, the authors wrote in their report. But overall, higher transmission rates don't change the overall pattern described in the model, mostly just how frequently mutants crop up and when they become established in the populace, they wrote. 

That said, the exact probability of whether an infected person will start churning out vaccine-resistant mutants is a "really big unknown," Kondrashov said. "This is probably the biggest unknown variable that we have in our model." Different individuals likely have slightly different chances of becoming hosts for troublesome mutants; for instance, immunocompromised people can sometimes shed the virus for months, during which time the virus gets many, many chances to mutate, studies suggest. 

Although the model doesn't precisely mimic reality, "I don't see any assumption [the authors made] that would change the main point, which again isn't surprising," Levy said. At a fundamental level, when a large proportion of people are vaccinated but transmission rates are high, that sets the stage for vaccine-resistant variants to emerge, he said. "The fact that we don't have a variant that is fully able to evade the mRNA vaccines yet does not mean that one won't come."

So what can we do to avoid this worst-case scenario?

For Kondrashov, the main takeaway is that "it's very much necessary to maintain non-pharmaceutical interventions," such as masking, "throughout the entire vaccine campaign, up to the very, very end." However, in the idealized model, every imaginary person in the population has an equal probability of getting vaccinated, it's just a matter of when, he noted. This doesn't capture a reality where children cannot yet be vaccinated and not all eligible adults are willing to be vaccinated. 

Since we don't live in a model, the authors instead recommend that people maintain measures like masking and distancing "for a reasonable period of time," even once the proportion of people vaccinated nears the herd immunity threshold, they wrote in their report. This would help drive resistant strains to extinction before they spread too far.

That aligns with the new guidelines from the Centers for Disease Control and Prevention (CDC), which state that fully vaccinated people should wear masks in public indoor spaces if there is "substantial" coronavirus transmission in their area. (You can track your county transmission rate on the CDC website.) That's because vaccinated people who catch delta may sometimes be able to spread the virus as easily as those who are unvaccinated.

Originally published on Live Science.