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    New BA.4.6 COVID Variant Is Shaping Up to Be a Deja Vu Nightmare

    The world has built up a lot of immunity in the nine months since the Omicron variant of the novel coronavirus became dominant, driving a record wave of infections.

    That immunity from vaccines and past infection is helping to keep down hospitalizations and deaths even as Omicron’s offspring—a succession of subvariants—have become dominant, one after one.

    Now the virus is trying to find a way around our antibodies. A new subvariant, BA.4.6, is beginning to outcompete its predecessor, BA.5. Its advantages include a particular mutation to the spike protein, the part of the virus that helps it to grab onto and infect our cells.

    We’ve seen this R346T mutation before. And every time it’s appeared, it’s been associated with forms of the SARS-CoV-2 pathogen with an increased ability to dodge our antibodies. A quality epidemiologists call “immune-escape.”

    If BA.4.6 becomes dominant, it could reverse the encouraging trend we’ve seen in most countries in recent weeks toward fewer infections, fewer hospitalizations, fewer deaths.

    It’s a reminder that the novel coronavirus is a living, evolving thing. As we adapt to it, it adapts to us. “Viruses in general mutate to be more infectious and to avoid our immunity,” Ali Mokdad, a professor of health metrics sciences at the University of Washington Institute for Health, told The Daily Beast.

    Don’t panic quite yet. “One thing I try not to do is get too excited for every new variant that pops up,” Peter Hotez, an expert in vaccine development at Baylor College, told The Daily Beast.

    Most coronavirus variants and subvariants appear and disappear without significantly changing the pandemic’s overall direction. Plus, there’s a new kind of vaccine in the works that could help us to fight, long-term, even the worst forms of COVID. Eventually.

    All the same, BA.4.6 warrants close attention. It’s the seventh major subvariant of Omicron, which first appeared in Africa back in November. It spread fast, outcompeting and replacing the previous major variant, Delta. Epidemiologists have described Omicron and its subvariants as the most contagious respiratory viruses they’ve ever seen.

    Omicron is four times as transmissible as Delta but half as lethal. So Omicron resulted in the worst-ever day for new COVID infections when a record 4.1 million people got sick on Jan. 19. That’s a fivefold increase over Delta’s worst day back in April last year.

    But just 13,000 people died on the worst day for Omicron deaths on Feb. 9—thousands fewer than died on Delta’s most lethal day back in January 2021.

    It’s not hard to explain the growing gap between infections and deaths as the pandemic grinds toward its fourth year. Billions of people have been at least partially vaccinated. Billions have caught COVID and survived. The combination of vaccine-induced and natural antibodies has created a global wall of immunity that has blunted the worst outcomes.

    But with BA.4.6, the virus is trying to find a way around that wall. “There’s a huge selective pressure for immune-escape, especially now that the great majority of the population has some degree of immunity, from immunization, infection or both,” Keith Jerome, a University of Washington virologist, told The Daily Beast.

    SARS-CoV-2 is, in essence, fighting for its own survival—trying out mutations until it settles on one that might give it the upper hand.

    R346T is one of those mutations. It’s not totally clear how the virus came up with the change. It’s possible Omicron mixed with an older form of SARS-CoV-2 in a person who’s gotten sick more than once. It’s possible, in other words, that BA.4.6 is a “recombinant” subvariant that picked up its most advantageous quality from one of its predecessors.

    That one change to the spike protein appears to make the virus somewhat harder for our antibodies to recognize. With R346T, the virus has a better chance of slipping right past our immune systems and causing an infection. Even if we’ve been vaccinated. Even if we’ve also caught and gotten over COVID in the past.

    Greater immune-escape means more and worse infections. We’ve been lucky with Omicron in the sense that, even as the variant and its subvariants have driven back-to-back-to-back waves in cases since November, hospitalizations and deaths haven’t risen in proportion.

    It’s still an open question how much worse BA.4.6 might be and how far it might spread. Health agencies all over the world have been tracking the subvariant for months now. As BA.5 cases plateau, BA.4.6 is outcompeting BA.5—but not everywhere.

    The BA.4.6 hotspots include some Australian states and parts of the U.S. Midwest. So far, BA.4.6 accounts for around four percent of new cases in the U.S., Canada and the United Kingdom.

    The proportion of BA.4.6 is set to rise as BA.5 declines. BA.4.6 appears to have only a 10-percent growth advantage over BA.5, but that advantage has been growing over time.

    If there’s good news in BA.4.6’s rise, it’s that for all its worrying mutations it’s still an Omicron sublineage—and still has a lot of mutations in common with BA.5, BA.4, BA.2 and BA.1.

    That means the Omicron-specific boosters that Pfizer and Moderna are developing for their messenger-RNA vaccines, and which U.S. regulators are on track to approve in coming weeks, should still work at least somewhat against BA.4.6.

    BA.4.6 isn’t the worst case scenario. That would be a subvariant—or brand-new variant—with strong immune-escape. A form of SARS-CoV-2 that has mutated so much that all those antibodies we’ve built up over the past three years barely recognize it.

    The epidemiological community is divided over how likely this variant is to evolve. Some are confident that respiratory viruses such as the flu and the novel-coronavirus tend to get overall milder over time as they become “endemic”—that is, always present but usually manageable.

    Others fear near-total immune-escape is all but inevitable for cleverer viruses as they tirelessly fight to survive. “This idea that each subsequent variant causes less severe illness—I don’t buy that,” Hotez said.

    The virus has been very successful so far.

    It comes down to genetics—the virus trading one quality for another as it strives to spread to more and more hosts. “The trick for the virus is to find a way to escape immunity while still maintaining the ability to infect new people efficiently,” Jerome explained.

    “The virus has been very successful so far at doing so, but the big question is whether it can continue to do so, or instead will ultimately exhaust all the possible tricks to do so, and settle down into a more manageable level of endemicity. There’s no way to know for sure yet.”

    A variant or subvariant with near-total immune-escape could drag us back to the most terrifying days of the early pandemic, when almost no one had immunity—or any way of developing immunity without surviving a very dangerous infection.

    But BA.4.6 with its R346T mutation and potential for immune-escape might be a preview of that worst-case scenario. It might also be an argument for the pharmaceutical industry and health agencies to redouble their efforts to create universal vaccines that work against SARS-CoV-2 and every other major coronavirus, of which there are scores.

    There are around a dozen major “pan-coronavirus” vaccines in development. The two leading efforts are at the Coalition for Epidemic Preparedness Innovations in Norway and the U.S. government’s National Institute of Allergy and Infectious Diseases.

    They’re spending $200 million and $43 million, respectively, to develop their new universal jabs. Trials are still months, if not years, away. “We’re moving piecemeal toward a more universal coronavirus vaccine,” Hotez said.

    Pan-coronavirus vaccines might be slightly less effective than the best mRNA vaccines were at their peak effectiveness (against serious illness and death) of more than 90 percent, back in late 2020.

    But they’d be broadly effective, keeping people alive and out of the hospital even as the virus mutates again and again in order to survive.

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