Unless you're a real-life virologist — or unless you enjoy playing one on Twitter — it has become pretty much impossible to keep up with all of the latest coronavirus variants.
First they were named after Greek letters, like Omicron. Easy enough. Then came a few short, Star Wars-esque alphanumerics, like BA.5. Fine.
But in recent weeks, COVID trackers have suddenly been subjected to a dizzying barrage of BA.4.6s and BF.7s and BA.2.75.2s and BQ.1.1s. There's even an ominous new sublineage called XBB.
For most Americans — the bulk of whom appear to be "over" COVID anyway — that's far too many numbers and letters to grasp. Easier to just tune it all out, they say. Call me when there's another wave on the way.
Well, now there might be.
The last big variant of concern — the hypertransmissible Omicron offshoot known as BA.5 — peaked in July. Since then, reported U.S. cases have plummeted by 70%. While far too many Americans are still dying of COVID each day — nearly 400, on average — the rate has returned to pre-BA.5 lows. It's a moment of relative calm.
But under the surface, something new — and potentially dangerous for the most vulnerable among us — has been happening: Omicron has started to "splinter."
As a result, we may be entering the next phase of the pandemic. Thanks to layers of immunity from vaccination and prior infection — plus lifesaving treatments such as Paxlovid — we will almost certainly never regress to the horrific era of collapsing ICUs and thousands of deaths per day.
Yet the orderly succession of individually dominant variants we've come to expect over the last two years — think Alpha, then Beta, then Delta, then Omicron — may also be a thing of the past.
Instead, what scientists are seeing now is a bunch of worrisome Omicron descendants arising simultaneously but independently in different corners of the globe — all with the same set of advantageous mutations that help them dodge our existing immune defenses and drive new waves of infection.
Experts call this "convergent evolution" — and right now, there's a "fairly unprecedented amount" of it going on, according to Tom Peacock, a virologist at Imperial College London.
"Although stuff started off in different places — some BA.2, some BA.5 — everything's going back in the same direction," Peacock recently told Stat. "They're getting the same mutations, which implies there's a very strong selective pressure in the environment right now, which of course is people's immunity."
"Clearly," he added in an interview with Nature, "there's an optimal way for a variant to look going into this season."
The problem is that what's optimal for the coronavirus usually isn't optimal for us.
Of all 300 post-BA.5 sublineages currently being monitored by the World Health Organization — a group that includes BA.4.6, BF.7 and BA.2.75, which have risen as a proportion of U.S. cases in recent weeks — experts are most concerned about two Omicron spinoffs that have barely even registered in America yet: BQ.1.1 and XBB.
"XBB and BQ.1.1 are 2 of the most important variants [to] watch right now," Eric Topol, founder of Scripps Translational Institute, tweeted last week.
Why? Because they're "escape" variants. While earlier sublineages that were jockeying for post-BA.5 supremacy in the U.S. had a few advantageous mutations, XBB, B.Q.1.1 and their ilk — including BN.1 and BA.2.75.2 — now boast at least six changes in just the right places on the virus's spike protein (leading some researchers to refer to them as the "pentagon" or "hexagon" variants). As a consequence, they now rank as the "most antibody-evasive" strains ever tested, according to Yunlong Richard Cao, an immunologist at Peking University in Beijing.
This is troubling for two reasons. The first is that the most vulnerable among us — the immunocompromised and the elderly — tend not to produce as strong or as lasting an antibody response after infection or vaccination. Monoclonal antibody treatments have helped fill the gap and shield them from severe illness.
But many of these treatments were abandoned after prior variants rendered them useless — and now lab experiments have shown that the remaining antibody therapies (bebtelovimab and Evusheld) don't work against XBB and B.Q.1.1. (Last week, the Food and Drug Administration warned that Evusheld can't neutralize the latest variants, meaning immunocompromised people may no longer be able to take it for pre-exposure protection.) Once the new escape variants take off, people at high risk for severe COVID are likely to be even more vulnerable than before (though not completely vulnerable as vaccination and prior infection still offer some defense against serious illness).
That leads to the second cause for concern: increased spread. Cao's experiments have shown that XBB in particular is "significantly more immune evasive … against plasma from all breakthrough infections" — including recent BA.5 infections — than other known variants. So while less vulnerable people might not get seriously ill if they catch B.Q.1.1 or XBB, vaccination and/or prior infection may be less likely than ever to stop them from catching it in the first place.
In turn, the more the virus circulates, the more chances it has to reach people who could get seriously ill — and as U.S. booster rates falter (less than 5% of eligible Americans have received the updated bivalent BA.5 shot) and as earlier vaccine protection wanes, the ranks of the susceptible may grow rather than shrink over the winter.
Finally, the fact that the virus is suddenly evolving in the same evasive direction everywhere at once suggests that most of the world should brace for impact sooner rather than later, regardless of which new sublineage happens to reach our particular patch of the planet. There are plenty of escape variants to go around.
Overseas, the next wave is already building. In the United Kingdom, BQ.1.1 infections are doubling every week, a rate of growth that far exceeds other leading sublineages; overall daily cases have doubled (on average) over the last month as well. Germany, France and Belgium are experiencing similarly rapid B.Q.1.1 growth, with the latter country facing a "wave [that's] well on track to match or even exceed [its] Omicron BA.1 wave," according to evolutionary biologist Tom Wenseleers.
Across Europe, from Italy to Austria to Sweden, COVID hospitalizations are already shooting up as the weather cools — and while B.Q.1.1 is outcompeting its rivals, it still has a ton of room for growth. Numbers are likely to get worse before they get better. Meanwhile, XBB is driving steep COVID case surges in Singapore and Bangladesh, two of the first countries where it has achieved dominance.
In the U.S., overall COVID cases are still going down. But XBB and B.Q.1.1 — the latter of which boasts an estimated daily growth advantage over BA.5 of 10% or higher — haven't really established a foothold here yet. One or both is likely to do just that, just in time for winter. As Cornelius Roemer, a respected tracker of pathogen evolution, recently put it on Twitter, it is becoming quite clear that we will see another "variant wave in Europe and North America before the end of November."
There's no reason to think America's latest winter wave will be as devastating — or even as disruptive — as its predecessors. Nearly all Americans have been vaccinated and/or exposed to the virus at this point, and both forms of immunity will continue to blunt severe disease and decouple deaths from cases. But Americans — especially the elderly and the immunocompromised — will be less protected than experts say they should be.
BQ.1.1 is a descendant of BA.5; XBB is a descendent of BA.2. By further broadening immunity, the new bivalent boosters are the best defense we have. Yet while about 93% of U.S. seniors have received their first two vaccine doses, just 45% have received their two recommended booster shots — and the number for bivalent boosters is much lower. CDC data has already shown that vaccine protection against COVID hospitalization fell from more than 80% to roughly 50 to 60% during the various Omicron waves. Without boosters — and with more evasive variants — it's likely to slip further.
For most U.S. residents, the new escape variants will be more of an inconvenience than a threat this winter. But even now, before they hit, nearly 400 (mostly older) Americans are still dying of COVID each day. That's almost 150,000 annually — about three times the death count of a bad flu year. How much death are we willing to normalize? And how much more should we tolerate this winter?
Which brings to mind a third reason these new escape variants are troubling: because they show us that, nearly three years in, the virus still has new tricks up its sleeve. Will Pi — another radically new variant like Omicron — come next? Or is this all part of the process of SARS-CoV-2 settling into some sort of cold-like stability? Or can both be true at the same time?
"Something is happening with SARS-CoV-2. Something big," evolutionary biologist Shay Fleishon wrote on Twitter earlier this month. "Put it this way — there was a range of possible scenarios that we expected for the near future. Positive and negative. The amplitude of that range is getting much (much) bigger."
"When scientists don't know [how] to explain stuff, it is the responsible thing to say — We don't know (yet)," Fleishon's tweet thread continued. "We can make contradicting hypotheses; we can make complicated maps & charts. But something is happening, much weirder than before. And we still don't know what it means."