A swarm of Covid variants could fuel the winter surge

This time, we are unlikely to be interrupted with a new collection of variants of the Greek alphabet. Instead, one or more versions of omicron variants that keep popping up may drive the next wave. They are different flavors of Omicron, but strangely similar — equipped with similar combinations of mutations. Each new subvariant appears to be greater than the last in its ability to dodge immune defenses.

“We have this constant evolutionary arms race with this virus,” said Jonathan Abraham, assistant professor of microbiology at Harvard Medical School.

The pace of evolution is so fast that many scientists rely on Twitter to keep up. Scientists were worried even a month ago BA.2.75, a variant that originated in South Asia and spawned a cloud of other sublineages. In the US, BA.4.6 and BF.7 have been slow pick up steam. A few weeks ago, BQ.1.1 started stealing the spotlight – and still looks like a contender to take over this fall in Europe and North America. is called a genus XBB Loom on the sidelines, and threaten to scratch the forecast.

Focusing too much on any one possible option, many experts argue, misses the point. The important thing is that all these new threats are accumulating mutations in the same place called Receptor binding domain — a key site on the spike protein where virus-blocking antibodies dock. If these antibodies cannot dock, they cannot block. Each new mutation gives the virus a leg up to avoid it First line of immune defense.

Most virologists balk when asked which strain – or strains – will infect humans this winter. It doesn’t mean they think the virus is fixed.

Most of the world’s population has acquired immunity due to vaccination and exposure to omicrons. That protection gave us a moment of relative freedom — many people returned to normal life. But the protection is transient due to two main reasons: waning immunity and the virus changing. And then there’s this: monoclonal antibodies, targeted drugs that can be used as treatments or to protect immunocompromised people who don’t respond well to vaccines, are likely to be knocked out by future variants.

“It’s important for people to understand that not having the Greek letter name doesn’t mean the virus has stopped evolving,” says Jesse Bloom, an expert on viral evolution at the Fred Hutchinson Cancer Research Center in Seattle. The evolutionary rate of SARS-CoV-2 is “surprisingly fast.”

Instead of worrying about which variant will win out, or even focusing on specific mutations, many scientists have turned to looking at hotspots — specific sites on the virus, known by street address-like numbers, where a change in the virus’s code might slip it. By neutralizing antibodies which are the first line of defense.

The coronavirus spike protein is made up of about 1,300 building blocks known as amino acids, and mutations that change even one building block can make it harder for antibodies to block the virus. Instead of the Greek alphabet, scientists maintain a short list of places of concern for mutations: 346, 444, 445, 452, 460, 486, 490.

Seeing similar constellations of genetic changes form at these spots in many lineages of coronaviruses is a sign of convergent evolution — when different versions of the virus bump into the human population’s immune system and then come up with similar means. It happens with influenza to get them close, but it is fairly new for SARS-CoV-2. And in the case of the coronavirus, the more mutations there are, the greater the advantage a new variant seems to have.

Cornelius Romer, a computational biologist at the University of Basel in Switzerland, ranked the new omicron sublineages based on how many mutations they had in the receptor binding domain.

XBB seems to be the best at avoiding immunity. Researchers in China have found that XBB can evade protective antibodies generated by a breakthrough BA.5 infection, raising concerns that Omicron’s BA.4 and BA.5 versions could quickly outpace fruit boosters developed to target them. Still, those booster shots remain top-shelf tools.

“At the current stage, we don’t have a better option,” Yunlong Cao, a scientist at Peking University’s Biomedical Pioneering Innovation Center in Beijing, said in an email.

Friday, Information The Centers for Disease Control and Prevention found that BQ.1 and BQ.1.1 made up about 11 percent of the viruses sampled in the United States. Whether it’s XBB, BQ.1.1, or some as-yet-unknown twist on omicron, most experts agree that the variants will help fuel a tough fall and winter.

“This strain has the ability to re-infect people more than what is currently going on … which could drive or contribute to a wave of infections in the winter,” Tom Peacock, a virologist at Imperial College London, said in an email.

What happens when one or more of them gets a foothold in a population with a protective layer of innate immunity is debatable. Protection against the worst outcomes is likely to hold, especially if boosted by boosters, many scientists predict.

Cases are already increasing in Europe. Many scientists believe the rise is largely driven by factors such as children going back to school, people spending more time indoors and the seasonality of viruses. Forms can only begin to contribute.

“We are certainly in a better place than we were many months ago; We are still in a downward trend in the United States, said Anthony S. Fauci, director of the National Institute of Allergy and Infectious Diseases, who urged people to get an updated booster if eligible. “We have to watch and follow these things very carefully, because we want to make sure we have a good handle on what’s happening in terms of the emergence of variants and what impact they will have on any trends we have. Going to visit in winter.”

But the impact on society can still be significant even in cases that do not lead to massive waves of hospitalizations.

“To put it in context, the summer wasn’t considered a wave — but at the same time, there were a lot of problems with absenteeism and that kind of thing that affected the whole world,” said Manon Ragnett-Cronin, a scientist at the University of Chicago. “The primary measure of how bad these waves are may be hospitalizations and deaths, but those other effects shouldn’t be discounted.”

Nothing is certain about a late-fall wave—whether one will occur, what its magnitude might be, or what it might spark. The new crop of variants obviously escapes immunity, but Justin Lesler, a professor of epidemiology at the University of North Carolina’s Gillings School of Public Health, says how the benefit plays out in the world will be a matter of course.

“One strain may have a growth advantage over other strains, but that’s not enough of an advantage to lead to a resurgent epidemic,” Lessler said.

What’s more predictable: Any variant that dominates in the coming months will likely challenge a mainline of treatment and protection for people with compromised immune systems — drugs known as monoclonal antibodies. Evushield is a long-acting version used to prevent illness in people with compromised immune systems. Another monoclonal, to bebtelovimabused as a treatment.

The pharmaceutical companies that make these drugs insist that they will remain effective against the variants now prevalent. But for many scientists, the writing is on the wall. Swarms on the horizon threaten to wipe out one or both of these therapies — and may even upset the next generation of candidates that haven’t yet made it into the medicine cabinet.

Regeneron Pharmaceuticals, a major maker of monoclonal antibodies, halted start-up activities in clinical trials for its new drug in late September — pointing not to a specific new lineage of Omicrons but to a mutation in one of the hotspots.

“We request that all start-up activities … be permitted to allow Regeneron to evaluate the new variant and its potential impact on our planned clinical development trials,” said a company memo sent to investigators running the trial.

Scientists worry that EVUSHEELD could be as useless by the end of the year as new Variant Occupied Food and Drug Administration Be warned this month That drug is less likely to protect against infection from BA.4.6, a strain that represents about 12 percent of viruses circulating in the United States.

Bebtelovimab, a monoclonal made by Lilly, may face a ticking clock like no other Mutation threatens to reduce its effectiveness.

Companies can choose from many libraries of monoclonal antibody drugs, but how to choose them, prove that they work, and whether they Safely has become more pressing because the drug has a Short shelf lifeDue to the speed of viral evolution.

In an effort to make their drugs more variant-proof, companies are trying to design antibody products that are not identical to the dominant antibodies that the human body naturally produces to root out the virus.

Laura Walker, chief scientific officer of Invivid, a biotechnology company working on monoclonal antibody drugs, described a compound her company hopes to begin testing in humans in January as “nature’s freak” — because it binds to an unusual spot. virus.

“You try to look ahead, and the question is: How far do those headlights go?” Dr. Walker.

Uninterrupted transmission of the virus will allow it to find vulnerable people – age or medical risk factors. It could also result in the wild-card scenario many experts fear: a new and very different variant could emerge from another branch of the coronavirus evolutionary tree.

A leading theory of the origin of Omicron is that it developed as a result of a long-term infection Immunocompromised patients — and the potential for giant leaps to occur again cannot be ignored.

“If we sit on our hands and say, ‘Well, we’re all fine,’ and forget about the vulnerable people who don’t develop good immunity, that could increase the likelihood of a new, virulent form emerging,” Abraham, Harvard , Dr. “I’m not sure if that will happen this winter, but I think it’s likely. There’s still a lot of room for evolution.”