(ORDO NEWS) — Emerging subvariants have received a combination of mutations that makes them more immune evasive than ever before
Nearly 3 years after the start of the pandemic, SARS-CoV-2 is facing a major challenge: to find new ways to bypass the immunity people have developed through vaccines and countless infections. New disturbing data shows that he is up to the task.
In recent weeks, the attention of scientists has attracted several new strains of the virus with high immunogenicity; one or more of them could very well cause new large waves of COVID-19 this fall and winter.
“We can say with certainty that something is coming. Perhaps several are coming at once,” says Cornelius Römer, who studies the evolution of viruses at the University of Basel. Whether they will also lead to numerous hospitalizations and deaths is a big question.
“It’s not surprising that we’re seeing changes that again help the virus evade the immune response,” says molecular epidemiologist Emma Hodcroft of the University of Berne, who notes that SARS-CoV-2 is facing “the same problem that such patients face every year.” illnesses like colds and flu – how to make it come back.”
The strains that seem poised to be the driving force behind the latest comeback are all sub-variants of the Omicron virus that swept the world last year.
Several of these are descended from BA.2, a strain that succeeded the original BA.1 Omicron, but was then superseded in most places by the BA.5 strain that dominated in recent months.
One of them, BA.2.75.2, seems to be spreading rapidly in India, Singapore and parts of Europe. Other new immunocompromising strains have evolved from BA.5, including BQ.1.1, which has been found in many parts of the world.
Despite their different origins, some of the new strains received a similar combination of mutations to help overcome the immune wall – a prime example of convergent evolution.
According to evolutionary biologist Jesse Bloom of the Fred Hutchinson Cancer Center, they all have changes at half a dozen key points in the viral genome that affect how well neutralizing antibodies from a vaccination or previous infection bind to the virus.
To quickly assess how well any new subvariant can evade immunity, the researchers create copies of the spike proteins of the viruses and expose them to monoclonal antibodies or human sera to measure how well the antibodies can block the variants from infecting cells.
Using such tests, researchers in China and Sweden have found that the BA.2.75.2 virus spike protein can effectively bypass almost all monoclonal antibodies used to treat COVID-19, suggesting that these treatments may not be useful.
Both groups also found that BA.2.75.2 seems to be very good at evading immunity in humans.
In a preprint published Sept. 19, immunologist Ben Murrell of the Karolinska Institute and colleagues reported that serum samples from 18 blood donors in Stockholm, where vaccination rates are high and pre-existing infections are common, were less than one-sixth effective in neutralizing BA. 2.75.2 compared to BA.5.
“It’s the most sustainable variant we’ve ever evaluated,” says Karolinska virologist Daniel Sheward.
Yunlong immunologist Richard Kao of Peking University and colleagues found similar results for BA.2.75.2 after analyzing blood samples from 40 people who received three doses of CoronaVac, an inactivated virus vaccine, and another 100 people who received the vaccine and then had breakthrough infections with BA.1, BA.2 or BA.5.
The team found that BQ.1.1 had an equally astonishing ability to evade antibodies.
In their preprint, updated Sept. 23, Cao and colleagues also report that the new variants do not appear to have lost the ability to tightly bind to the receptor on human cells that the virus uses to infect, meaning that the infectivity of the variants most likely has not decreased.
They also report some evidence that infections with these variants produce proportionately more of the wrong types of antibodies – those that bind tightly to the virus but do not impair its ability to infect cells.
All this may herald a new massive wave, says Cao. “There has never been such a scale of immunity evasion, and the virus continues to evolve rapidly,” he says. “This is very bad”.
Shevard and Murrell agree that a lot of infections should be expected in the next few months, as happened last winter when Omicron came on the scene.
But they are less pessimistic than Cao, noting that many more people have already recovered from the infection or received additional doses of the vaccine, including the specific Omicron vaccines that began distribution this month.
This will increase overall antibody levels and likely expand the antibody repertoire, Sheward says: “I don’t think we’re back to square one.”
“The choice to add BA.5 to vaccine boosters still looks right,” adds Bloom. “Boosters will always be one step behind, but the good news is that the BA.5 booster will be one or two steps behind the evolution of the virus, not five steps.”
Just how brutal the return of the coronavirus has been will become clear as more people become infected with the new strains. The next wave may also provide more precise clues about what factors cause or prevent severe disease, Murrell says: “I think we’ll learn a lot this winter.”
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