HOW DO WE PREPARE FOR NEXT COVID-19 VARIANT?
‘We aren’t adequately humbled by what we don’t know about it,” Winnipeg internal medicine doctor Jillian Horton recently tweeted about the coronavirus that keeps surprising. First BA.1, then BA.2, now, a new Omicron offshoot, BA.2.12.1, is making its presence known in the U.S. where it’s driving a spike in cases in New York State. How do COVID-19 variants emerge, why do some take hold while others disappear and what could be coming next? Here’s some of what scientists do — and don’t — know.
HOW DOES A CORONAVIRUS MUTATE TO GENERATE NEW VARIANTS?
SARS-COV-2 enters the human body through the respiratory tract. It finds a healthy target cell that has receptors on its surface, in this case, the ACE2 receptor, that it docks onto, and slips inside the cell. Once inside, the virus starts replicating, copying its genetic code over and over again.
The replication process for any organism is prone to errors, to typos. Coronaviruses have a proofreading enzyme that corrects mistakes. It mutates slower than other viruses, but still at a rate fast enough to produce plenty of mutations that occur randomly. Many are harmless. Others give the virus a competitive edge. Alpha, then Delta and now Omicron rapidly displaced each other on their way to supremacy. Compared to the original strain, they have been more infectious, more virulent, more resistant to natural or vaccine elicited immunity, or some combination of all three.
The more opportunities a virus is given to replicate in humans, and leap from human to human, the more we increase the probability of generating viruses with mutations in new parts of its genome, University of Ottawa virologist Marc-andré Langlois explained during a recent panel discussion hosted by Canada’s COVID-19 Immunity Task Force and the Coronavirus Variants Rapid Response Network, or COVARR-NET.
WHERE ARE THE COVID VARIANTS COMING FROM?
In regions with high levels of infection, and the immunocompromised who don’t respond as well to vaccines and who have a hard time shaking COVID if they do get infected. The longer a virus lingers in the body, the more time to pile on mutations. Doctors have described cases where immunocompromised people with persistent Covid-infections of 100 days or more generated highly mutated variants that seemed a form of “saltational” evolution, where an organism makes sudden large leaps between generations. “It’s as if you all-of-a-sudden go from walking to flying, with nothing in between,” virologist Dr. Larry Corey of Seattle’s Fred Hutchinson Cancer Research Center told Fred Hutch News Service.
HOW MANY MORE MUTATIONS CAN SARS-COV-2 UNDERGO?
It’s wishful thinking to imagine SARS-COV-2 is running out of steam, that its evolution is somehow done, “because we are so culturally and politically, and economically done with it,” COVID-19 modeller Caroline Colijn, of Simon Fraser University, said in an earlier interview. “I think evolution will continue to act. The way to stop evolution from giving us more variants is to reduce the size of the virus populations, and that’s infections. That’s not just hospitalizations.”
“There is no organism that stands still,” said Jesse Shapiro, an assistant professor in Mcgill University’s department of microbiology and immunology and COVARR-NET member. “Everything continues to mutate and adapt. It will continue to do so. That’s what flu does. That’s to be expected. It shouldn’t be alarming.” The question, said Shapiro, is: Is there a limit to its intrinsic transmissibility, which is already really, really high. Will it go even higher? “That’s what selection will always be promoting — every time there is a variant that can replicate faster, it will be selected and will take off. It’s hard to know what the limit will be.”
WHAT COULD COME NEXT?
A virus can change two ways: antigenic “drift,” meaning small, subtle changes or mutations, like we’re seeing with the BA-2’S. The other change is a shift, an abrupt, major change. Omicron was a shift, not a drift. “Omicron is not related to any of the Deltas,” Shapiro said. “It branched off way, way earlier, probably in mid-2020, and had been simmering in an unsampled population, or an animal reservoir, or an immune-compromised person, or some combination, and then it emerged.”
The next big variant could come directly descended from Omicron, or be wildly divergent, from another deep branch, and people shouldn’t hang their hats on Omicron’s lower severity, three researchers write in Nature Reviews. It’s “nothing but a lucky coincidence” that Omicron causes milder disease. They predict SARSCOV-2 will keep honing its ability to reinfect immune people. “Once Omicron infects the majority of individuals, the next variant will need to be as antigenically different from Omicron and previous (variants of concern) as possible to overcome immunity against them.” The possibility of a variant “featuring the potentially disastrous combination of the ability to reinfect due to immune escape along with high virulence is unfortunately very real.”
It’s all very unpredictable, Shapiro said. There’s no pressure on the virus to become more severe, or less severe. “The virus doesn’t really care if it’s more or less virulent or the same.” If it’s so virulent that it kills people before they’re able to transmit, “that’s a dead end, from the perspective of the virus.”