Emerging subvariants have hit on a combination of mutations that makes them more immune evasive than ever.

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.”

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