Yet Another Curveball in the COVID Mutation Nightmare 

“With each major variant that has been identified, we are seeing mutations outside of [the] spike that we are trying to figure out,” Matthew Frieman, a University of Maryland School of Medicine immunologist and microbiologist and lead author of the new study, told The Daily Beast.

It’s possible the virus is accumulating non-spike mutations in an attempt to gain some advantage over our collective immunity as the COVID pandemicgrinds toward its fourth year. These new mutations might not make the virus more infectious the way spike mutations do, but they could be associated with longer infections.

Viruses don’t do things by accident.” Instead, they try out small changes, over and over, until some combination of changes helps it survive and spread. The resulting variant or subvariant then outcompetes other forms of the pathogen until it becomes dominant—and the likely basis for the next set of mutations. To understand the reason for, and effects of, the non-spike mutations, Frieman’s team cloned SARS-CoV-2 then started deleting the spike proteins and testing the resulting “deletion viruses” on mice, assessing how contagious the viruses were and how severe the infections were. Their conclusion? “Mutations outside of [the] spike may be driving critical phenotypes of SARS-CoV-2 infection and disease.” That is to say, changes beyond the spike are beginning to define the virus.

Speed matters. The Omicron variant and its rapid-fire subvariants, each coming just a couple months after the last, was a warning that our pharmaceutical research-and-development processes might be too slow. Note that the U.S. Food and Drug Administration just last week green-lit Omicron-specific vaccine boosters—a full 10 months after the initial Omicron variant first became dominant. “Omicron and its lineages”—another term for subvariants—“taught us a lesson for the need to be more agile in modifying the vaccine,” Ali Mokdad, a professor of health metrics sciences at the University of Washington Institute for Health, told The Daily Beast.

As the virus continues trying out mutations in order to stay ahead of our spike-focused immunity, it might further emphasize changes beyond the spike. BA.5, with its wide breadth of mutations, is a sign that’s already happening.

There’s another wrinkle. These accumulating mutations across the novel-coronavirus—on the spike and not on the spike—could start to mess with the polymerase chain-reaction tests we use to detect and track the virus.

PCR tests and sequencing use primers tailored for a certain range of viral characteristics. Too many mutations “can mess with the PCR test,” Niema Moshiri, a geneticist at the University of California-San Diego, told The Daily Beast.

Pay attention, but don’t panic. It’s really no surprise that SARS-CoV-2 is trying out mutations on different parts of the virus. That’s what viruses do—adapt. The trick for us, the novel-coronavirus’s host, is to adapt at least as quickly.

New variants of a virus become dominant through radical mutations that significantly change how the pathogen behaves—and give it a leg-up over its predecessors. With every new variant, there’s a chance it’s changed so much that our antibodies no longer recognize it. “A major genetic shift that would greatly increase its ability to infect humans regardless of vaccination status and prior infections,” according to Alberg. Epidemiologists call that “immune escape.” It’s the nightmare scenario when it comes to viruses.

Daily BEAST, August

The Daily Beast

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