Main menu


Lots of covid variants could fuel a winter surge

featured image


Over the course of two years, variants of the coronavirus that swept the world emerged one by one.

But this fall and winter are expected to be different: Instead of a single sinister variant lurking on the horizon, experts are nervously staring at a swarm of viruses. and a new evolutionary stage in the pandemic.

This time around, it’s unlikely we’ll be flooded with a new collection of Greek alphabet variants. Instead, one or more versions of the constantly emerging omicron variant could drive the next wave. They’re different flavors of Omicron, but they’re eerily similar – adorned with a similar combination of mutations. Each new subvariable seems to outpace the last in its ability to circumvent immune defenses.

“It’s the constant evolutionary arms race we’re having 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. A month ago, scientists were concerned about BA.2.75, a variant that originated in South Asia and formed a cloud of other related sublineages. In the United States, BA.4.6 and BF.7 are slowly gaining momentum. a few weeks ago, BQ.1.1 has begun to steal the spotlight – and it still looks like a competitor to take over in Europe and North America this fall. A lineage called XBB looms over the edge and threatens to confuse the estimates.

Focusing too much on any one possible variable is missing the point many experts argue. The point is that all these new threats accumulate mutations at similar points, called the receptor-binding domain, which is a key point in the spike protein to which virus-blocking antibodies dock. If these antibodies cannot be coupled, they cannot block. Each new mutation gives the virus a foothold to evade this primary line of immune defense.

Most virologists hesitate when asked which variants – or variants – will infect humans this winter. This does not mean that they think the virus is still standing.

Most of the world’s population is immune to some extent due to vaccines and omicron infections. This protection gave us the relative freedoms of the moment, with many returning to normal life. But protection is temporary for two main reasons: immunity decreases and the virus changes. And there’s also this: Monoclonal antibodies, targeted drugs that can be used as a treatment or to protect immunocompromised people who don’t respond well to vaccines, will likely be neutralized by future variants.

“It’s important for people to understand that the absence of a Greek letter name does not mean that the evolution of the virus has stopped,” said Jesse Bloom, a viral evolution specialist at the Fred Hutchinson Cancer Research Center in Seattle. The evolutionary pace of SARS-CoV-2 is “strikingly fast.”

Instead of worrying about which variant will win, or even focusing on specific mutations, many scientists have switched to monitoring hotspots for specific sites on the virus, known by numbers, such as a street address, where any change in the virus’s code could allow the virus to slip. by neutralizing antibodies, which are the first line of defense.

The coronavirus spike protein is made up of about 1,300 building blocks called amino acids, and mutations that change even a single building block can make it harder for antibodies to block the virus. Instead of a Greek alphabet, scientists keep short lists of worrying spots for mutation: 346, 444, 445, 452, 460, 486, 490.

Seeing so many strains of the coronavirus develop similar constellations of genetic changes at these points is a sign of convergent evolution – when different versions of the virus hit the immune defense wall in the human population and then find similar pathways. go around them. This happens with influenza but is fairly new to SARS-CoV-2. And in the case of the coronavirus, more mutations seem to be the greater advantage of a new variant.

Cornelius Roemer, a computational biologist at the University of Basel in Switzerland, ranks the new omicron subclades by the number of mutations they have in the receptor-binding domain.

XBB seems to be the best at escaping immunity. Researchers in China have discovered that XBB can get rid of protective antibodies produced by a breakthrough BA.5 infection, raising concern that fall boosters designed to target the BA. Still, these supporting shots remain the best tool on the shelf.

“We don’t have a better option right now,” said Yunlong Cao, a scientist with the Biomedical Pioneer Innovation Center at Peking University in Beijing, in an email.

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

Tom Peacock, a virologist at Imperial College London, said in an email, “These strains will have the ability to reinfect more people than currently circulating…

What happens when one or more of them are grounded in a population with an underlying protective layer of immunity is a matter of debate. Many scientists predict that protection against the worst consequences will continue, especially if supplemented with boosters.

Cases are already on the rise in Europe. Many scientists think the rise is largely due to factors such as children returning to school, people spending more time at home, and the seasonality of the virus. Variants may have just begun to contribute.

“We are definitely in a better place than we were months ago; We’re still on a downward trend in the United States,” said Anthony S. Fauci, director of the National Institute of Allergy and Infectious Diseases, and encouraged people to buy an updated booster if appropriate. “We need to watch and monitor these things very carefully because we want to make sure we have a good grasp of what’s going on with the emergence of variants and what impact they will have on any trend. I’ll see you in winter.”

But even if there is an increase in cases that do not lead to a large wave of hospitalizations, the impact on society can still be significant.

“To put it in context, summer wasn’t considered a wave – but at the same time, there were a lot of issues with absenteeism and that sort of thing had an impact on the world as a whole,” Manon said. Ragonnet-Cronin is a University of Chicago scientist. “Our primary measure of how bad these waves are tends to be hospitalizations and deaths, but these other effects shouldn’t be ruled out.”

Nothing definite about the late autumn wave – whether a wave will occur, what its size may be, or what may trigger it. The new variant crop is clearly evading immunity, but Justin Lessler, professor of epidemiology at the University of North Carolina Gillings School of Public Health, said the question will be how this advantage will play out in the world.

“A strain may have a growth advantage over other strains, but still not have an advantage that would lead to a resurgent epidemic,” Lessler said.

What’s more predictable: Any variant that will become dominant in the coming months will likely challenge an important line of treatment and protection for people with compromised immune systems – drugs known as monoclonal antibodies. Evusheld is a long-acting version used to prevent illness in people with compromised immune systems. Another monoclonal, bebtelovimab, is used as a treatment.

Pharmaceutical companies that make these drugs emphasize that they are useful against currently common variants. But for many scientists, the writing is on the wall. The swarm on the horizon threatens to eliminate one or both of these treatments – and may even upset the next generation of candidates who may not yet find their way into the medicine cabinet.

Regeneron Pharmaceuticals, a major manufacturer of monoclonal antibodies, halted initial activities in clinical trials for its new drug in late September – which pointed to a mutation in one of the hotspots, not a specific new lineage of omicrons.

In a company memo sent to the researchers running the trials, “We would like all initial activity to be paused… to allow Regeneron to evaluate the new variant and its potential impact on our planned clinical development trials.”

Scientists are concerned that Evusheld may be useless by the end of the year as new variants take over. The Food and Drug Administration warned this month that the drug is unlikely to protect against infections 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 as other mutations threaten to undermine its effectiveness.

Companies can choose from many libraries of monoclonal antibody drugs, but questions about how to choose them, whether they work and whether they work. As it became clear that drugs have short shelf lives due to the speed of viral evolution, it became more urgent that they were safe.

To make their drugs more resistant to variants, companies are trying to design antibody products that do not resemble the dominant antibodies that the human body naturally creates to destroy the virus.

Laura Walker, chief scientific officer of Invivyd, a biotech company working on monoclonal antibody drugs, described one of the compounds her company hopes to begin testing in humans in January as a “nature freak”—because it attaches to an unusual point. virus.

“You want to try and look ahead and the question is: how far do these headlights go?” said Walker.

Unabated transmission of the virus will allow it to find vulnerable people, whether due to age or medical risk factors. It could also result in the wildcard scenario that many experts fear: A new and very different variant could emerge from another branch of the coronavirus evolutionary tree.

A leading theory for the origin of the Omicron is that it evolved as the result of a prolonged infection in an immunocompromised patient – and the possibility of a big leap again cannot be ruled out.

“If we sit in our hands and say, ‘Well, we’re all fine,’ and forget about vulnerable people who don’t have good immune responses, this can increase the likelihood that a new, more dire variant will emerge,” Abraham said. “From Harvard,” he said. “I’m not sure if it will happen this winter, but I think it’s likely. There is still a lot of room for evolution.”