The world has built up a lot of immunity in the nine months since the Omicron variant of the new coronavirus became dominant, triggering a record wave of infections.
That immunity to vaccines and previous infections helps limit hospitalizations and deaths, even as Omicron’s offspring — a succession of subvariants — have become dominant one by one.
Now the virus is trying to find a way to bypass our antibodies. A new sub-variant, BA.4.6, is starting to surpass its predecessor, BA.5. Its benefits include a particular mutation in the spike protein, the part of the virus that helps it grab hold of and infect our cells.
We have seen this R346T mutation before. And every time it has appeared, it has been linked to forms of the SARS-CoV-2 pathogen with an increased ability to evade our antibodies. A high-quality epidemiologists call “immune flight.”
If BA.4.6 becomes dominant, it could reverse the encouraging trend we’ve seen in most countries in recent weeks towards fewer infections, fewer hospitalizations, fewer deaths.
It reminds us that the novel coronavirus is a living, evolving thing. If we adapt to it, it adapts to us. “Viruses generally mutate to be more contagious and to avoid our immunity,” Ali Mokdad, a professor of health sciences at the University of Washington Institute for Health, told The Daily Beast.
Don’t panic yet. “One thing I try not to do is get too excited for every new variant that pops up,” Peter Hotez, a vaccine development expert at Baylor College, told The Daily Beast.
Most variants and sub-variants of the coronavirus appear and disappear without significantly changing the overall direction of the pandemic. In addition, a new kind of vaccine is in the works that could help us fight even the worst forms of COVID in the long term. Possibly.
Yet BA.4.6 deserves a lot of attention. It is the seventh major sub-variant of Omicron, which first appeared in Africa in November. It quickly spread, surpassing and replacing the previous major variant, Delta. Epidemiologists have described Omicron and its subvariants as the most contagious respiratory viruses they have ever seen.
Omicron is four times more transmissible than Delta, but half as deadly. So Omicron Resulted In Worst Day Ever For New COVID infections when a record 4.1 million people became ill on January 19. That’s a fivefold increase from Delta’s worst day in April last year.
But only 13,000 people died on the worst day for Omicron deaths on February 9 – thousands less than died on Delta’s deadliest day in January 2021.
It is not difficult to explain the growing gap between infections and deaths as the pandemic approaches its fourth year. Billions of people are at least partially vaccinated. Billions have contracted COVID and survived. The combination of vaccine-induced and natural antibodies has created a global wall of immunity that has blunted the worst results.
But with BA.4.6, the virus tries to find a way around that wall. “There is tremendous selective pressure to escape the immune system, especially now that the vast majority of the population has some degree of immunity, against immunization, infection, or both,” Keith Jerome, a virologist at the University of Washington, told The Daily Beast.
SARS-CoV-2 is essentially fighting for its own survival – trying out mutations until it settles on one that could give it the upper hand.
R346T is one of those mutations. It’s not entirely clear how the virus came up with the change. It is possible that Omicron may have been mixed with an older form of SARS-CoV-2 in a person who has become ill more than once. In other words, it is possible that BA.4.6 is a “recombinant” subvariant that has inherited its most advantageous quality from one of its predecessors.
That one change to the spike protein turns out to be a bit more difficult for our antibodies to recognize. With R346T, the virus has a greater chance of slipping past our immune system and causing an infection. Even if we are vaccinated. Even if we also caught and conquered COVID in the past.
More immune escape means more and worse infections. We’ve been lucky with Omicron in that while the variant and its sub-variants have been driving back-to-back-to-back waves in cases since November, hospitalizations and deaths have not increased proportionately.
It’s still an open question how much worse BA.4.6 could be and how far it could spread. Health authorities around the world have been monitoring the subvariant for months. Since BA.5 has fallen, BA.4.6 trumps BA.5, but not everywhere.
The BA.4.6 hotspots include some Australian states and parts of the US Midwestern United States. So far, BA.4.6 accounts for about four percent of new cases in the US, Canada and the UK.
The share of BA.4.6 will increase as BA.5 decreases. BA.4.6 only appears to have a 10 percent growth advantage over BA.5, but that advantage has grown over time.
If there’s any good news in the rise of BA.4.6, it’s that for all its worrying mutations, it still an Omicron subline – and still shares many mutations 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, which US regulators will approve in the coming weeks, should still work at least somewhat against BA.4.6.
BA.4.6 is not the worst case scenario. That would be a sub-variant – or a brand new variant – with a strong immune escape. A form of SARS-CoV-2 that is so highly mutated that all the antibodies we’ve built up over the past three years barely recognize it.
The epidemiological community is divided on how likely it is that this variant will evolve. Some are convinced that respiratory viruses such as the flu and the novel coronavirus tend to generally soften over time as they become “endemic” — that is, ever-present but usually manageable.
Others fear that a near-total immune system escape is almost inevitable for smarter viruses that fight tirelessly for survival. “I don’t believe the idea that each subsequent variant causes less severe disease,” Hotez said.
“The virus has been very successful so far.”
It comes down to genetics – the virus trades 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 efficiently infect new people,” explains Jerome.
“The virus has been very successful at that so far, but the big question is whether it can continue to do this, or if instead it will eventually exhaust all possible tricks and settle into a more manageable level of endemism. There’s no way to know for sure yet.”
A variant or subvariant with near-total immune system escape could drag us back to the most terrifying days of the early pandemic, when hardly anyone had immunity – or any way to develop immunity without surviving a very dangerous infection.
But BA.4.6 with its R346T mutation and immune escape potential could be a preview of that worst-case scenario. It could also make a case for the pharmaceutical industry and health authorities to redouble their efforts to create universal vaccines that work against SARS-CoV-2 and every other major coronavirus, of which there are dozens.
There are about a dozen major “pan-coronavirus” vaccines in development. The two leading efforts are those of the Coalition for Epidemic Preparedness Innovations in Norway and the US government’s National Institute of Allergy and Infectious Diseases.
They are spending $200 million and $43 million respectively to develop their new universal jabs. Trials are months, if not years, away. “We are moving towards a more universal coronavirus vaccine bit by bit,” Hotez said.
Pan-coronavirus vaccines may be slightly less effective than the best mRNA vaccines that had peak effectiveness (against severe illness and death) of over 90 percent at the end of 2020.
But they would generally be effective, keeping people alive and out of hospital even as the virus keeps mutating to survive.