Nearly 3 years into the pandemic, SARS-CoV-2 faces a formidable challenge: finding new ways around the immunity humans have built up through vaccines and countless infections. Worrisome new data show it is up to the challenge. Several new and highly immune-evasive strains of the virus have caught scientists’ attention in recent weeks; one or more may well cause big, new COVID-19 waves this fall and winter.
“We can say with certainty that something is coming. Probably multiple things are coming,” says Cornelius Roemer, who studies viral evolution at the University of Basel. Whether they will also lead to many hospitalizations and deaths is the big question.
“It’s not surprising that we’re seeing changes that yet again help the virus to evade immune responses,” says molecular epidemiologist Emma Hodcroft of the University of Bern, who notes that SARS-CoV-2 faces “the same challenge that things like the common cold and influenza face every year—how to make a comeback.”
The strains that look poised to drive the latest comeback are all subvariants of Omicron, which swept the globe over the past year. Several derived from BA.2, a strain that succeeded the initial BA.1 strain of Omicron but then was itself outcompeted in most places by BA.5, which has dominated in recent months. One of these, BA.2.75.2, seems to be spreading quickly in India, Singapore, and parts of Europe. Other new immune-evading strains have evolved from BA.5, including BQ.1.1, which has been spotted in multiple countries around the globe.
Despite their different origins, several of the new strains have chanced upon a similar combination of mutations to help scale the wall of immunity—a striking example of convergent evolution. They all have changes at half a dozen key points in the viral genome that influence how well neutralizing antibodies from vaccination or previous infection bind to the virus, says evolutionary biologist Jesse Bloom of the Fred Hutchinson Cancer Center.
To quickly gauge how well any new subvariant may evade immunity, researchers make copies of the viruses’ spike proteins and expose them to monoclonal antibodies or sera from people to measure how well the antibodies can block the variants from infecting cells. Using such tests, researchers in China and Sweden have found that spike protein from BA.2.75.2 can effectively evade nearly all the monoclonal antibodies used for treating COVID-19, suggesting these treatments may become useless.
Both groups also found that BA.2.75.2 seems very good at evading immunity in humans. In a preprint posted on 19 September, immunologist Ben Murrell at the Karolinska Institute and his colleagues reported that serum samples from 18 blood donors in Stockholm—where vaccination rates are high and prior infections widespread—were less than one-sixth as effective at neutralizing BA.2.75.2 compared with BA.5. “This is the most resistant variant we’ve ever evaluated,” says Karolinska virologist Daniel Sheward.
Immunologist Yunlong Richard Cao at Peking University and his colleagues found similar results for BA.2.75.2 after testing blood samples from 40 people who had been vaccinated with three doses of CoronaVac, a vaccine made from inactivated virus, and 100 more who had been vaccinated and then had breakthrough infections with BA.1, BA.2, or BA.5. The team found that BQ.1.1 had a similarly striking ability to evade antibodies.
In their preprint, updated on 23 September, Cao and his colleagues also report that the new variants do not seem to have lost any ability to bind tightly to the receptor on human cells that the virus uses to infect them, which means the variants’ infectiousness has likely not decreased. And they report some evidence that infections with the variants trigger proportionally more of the wrong types of antibodies—those that bind tightly to the virus but don’t blunt its ability to infect cells. All of that could portend a massive new wave, Cao says. “The scale of immune evasion has never been seen before, and the virus is still rapidly evolving,” he says. “It’s very bad.”
Sheward and Murrell agree we should expect lots of infections in the next few months, as happened last winter when Omicron entered the scene. But they’re less pessimistic than Cao, noting that many more people have recovered from an infection now or have received additional vaccine doses, including Omicron-specific boosters, whose rollout began this month. Those will boost overall antibody levels and will likely broaden the antibody repertoire, Sheward says: “I don’t think we’re quite back to square one.”
“The choice to put BA.5 in the vaccine booster is still looking like a good one,” Bloom adds. “The boosters are always going to be a step behind, but the good news is that the BA.5 booster is going to be one or two steps behind the virus’ evolution, instead of five steps behind.”
Just how brutal a comeback the coronavirus has managed will become clear once more people become infected with the new strains. The next wave may also provide better clues about what factors trigger or prevent severe disease, Murrell says: “I think we’re going to learn a lot this winter.”