XBB.1.5 FAQ: What you should know about the latest Omicron subvariant

You’ve probably seen it in the news this week: XBB.1.5 is the latest Omicron subvariant to spread rapidly through the U.S.

It is, of course, more transmissible and more capable of evading immunity from past infections than other versions of Omicron that have gone before it, as this lineage continues mutating. Scientists are still learning about XBB.1.5; it emerged from the U.S. during the holiday season, which has posed surveillance challenges. But we know enough to say that this variant is bad news for an already overstretched healthcare system.

Here’s a brief FAQ post on XBB.1.5.

Where did XBB.1.5 come from?

XBB, the parent of this latest lineage, emerged in Asia in October 2022. It evolved from Omicron BA.2 via recombination, which basically means two different BA.2 subvariants fused—likely while the same person was infected with both—and formed this new strain. (See my variants post from October for more details on XBB.)

XBB started spreading and mutating in the U.S. a few weeks later, leading to XBB.1.5. This subvariant was first identified in New York State in mid-December, though it could have evolved elsewhere in the northeast (since New York has better variant surveillance than some other states). Eric Topol’s newsletter has more details about XBB evolution.

What are XBB.1.5’s advantages compared to other variants?

It spreads faster, likely because it is more capable of evading immune system protections from past infection or vaccination than other Omicron subvariants. In the U.S., CDC data suggests that XBB.1.5 is starting to outcompete other lineages in the “Omicron variant soup” we currently have circulating.

BQ.1.1 and XBB (original) were already known to be the best-evolved subvariants in this area before XBB.1.5 came along, according to this December 2022 paper in Cell. XBB.1.5 has taken this immune escape further, as it evolved a mutation called F486P that’s tied to this property.

“It’s crazy infectious,” Paula Cannon, a virologist at the University of Southern California, told USA TODAY reporter Karen Weintraub. Cannon added that protections that have worked against other coronavirus strains for the last three years will likely be less effective against XBB.1.5 and other new variants.

What questions are scientists currently working to answer about XBB.1.5?

One major question that arises with any new subvariant is severity: will XBB.1.5 have a higher capacity to cause severe symptoms than other coronavirus lineages? (We now know, for example, that Delta was more severe compared to prior variants.)

The World Health Organization is currently working on a report about XBB.1.5’s severity, according to POLITICO. Scientists and public health officials will also study whether current COVID-19 treatments work against this subvariant. Antiviral treatments Paxlovid and Mulnopiravir likely won’t be impacted, but Omicron’s continued evolution has put a lot of restrictions on monoclonal antibodies.

Another important question will be how well our updated booster shots work against XBB.1.5. The shots used in the U.S. were primed for BA.4 and BA.5, while XBB is derived (albeit indirectly) from BA.2, so our shots are not the best match. Still, antibody neutralization studies have shown that the shots provide protection against XBB, meaning some impact on XBB.1.5 is likely. This is a great time to get your booster if you haven’t yet.

What impact is XBB.1.5 currently having in the U.S.?

The subvariant caused about 28% of new cases in the week ending January 7, according to CDC estimates. These estimates have a fairly wide confidence interval, though, meaning that XBB.1.5’s true prevalence could be between 14% and 47%; the CDC will improve these estimates in the coming weeks as it collects more XBB.1.5 samples.

But we know with more confidence that XBB.1.5 has already taken over in the Northeast. It’s causing the vast majority of cases in HHS Region 1 (New England) and Region 2 (New York and New Jersey). Other mid-Atlantic states are catching up.

Some experts have noted that New York and other Northeast states are currently reporting rising COVID-19 hospitalizations, which could be a sign that XBB.1.5 causes more severe disease. It’s currently unclear how much the increased hospitalizations may be attributed to XBB.1.5’s presence, though, as the entire country is seeing this trend already in the wake of the holidays.

Sam Scarpino, a disease surveillance expert at Northeastern University, has a helpful Twitter thread explaining this issue. “It’s clear that XBB.1.5 is correlated [to] an increase in hospitalizations in many highly vaccinated states,” he writes. “I suspect it will hit harder in states with lower bivalent booster rates.”

Why has XBB.1.5’s prevalence been harder to pin down than other subvariants?

Many of the news articles you might have read this week about XBB.1.5 cited that the subvariant’s prevalence more than doubled in about one week, according to CDC estimates. But then the CDC’s estimates were revised down this week, suggesting that XBB.1.5 actually caused 18% of new cases in the last week of December—not 41%.

Why did the estimate change so dramatically? Well, it actually didn’t: as the CDC itself pointed out in its Weekly Review newsletter this Friday, the 41% estimate had a big confidence interval (23% to 61%), so the revision down to 18% was not far outside the existing realm of possibility. The CDC revises its variant estimates constantly as new data come in; this might be a bigger shift than we’re used to seeing, but it’s still pretty unsurprising.

The CDC’s variant forecasting team is also facing a couple of challenges unique to XBB.1.5 right now. First, this is a homegrown, U.S.-derived variant, so they don’t have a wealth of international sequences to analyze in preparation for a U.S. surge. And second, XBB.1.5 arose during the holidays, when a lot of COVID-19 testing and sequencing organizations were taking time off. The CDC is currently working with very limited data, but it will continue to revise estimates—and make them more accurate—as more test results come in.

For more info on the CDC’s process here, I recommend this Twitter thread from epidemiologist Duncan MacCannell:

Also, as always when it comes to the CDC’s variant data, please remember that Eric Feigl-Ding is not a reliable source and shouldn’t be amplified.

How will XBB.1.5 impact the next phase of the pandemic?

Scientists will be closely watching to see how quickly XBB.1.5 spreads in other parts of the U.S., as well as how it performs in other countries that recently had surges of other Omicron subvariants.

Overall, the data we have about this subvariant so far suggest that it’s not distinct enough from other versions of Omicron to drive a massive new surge on the level of Omicron BA.1 last winter. But it’s still arriving in the wake of holiday travel and gatherings—and in a country that has largely abandoned public health measures that stop the virus from spreading.

In New York, for example, XBB.1.5 might not be the main cause of rising hospitalizations. Yet it is undoubtedly making more people sick with COVID-19, at a time when this region also faces continued healthcare pressure from flu and RSV. And an impending nurses’ strike won’t help the situation either, to put it mildly.

I think this Twitter thread from T. Ryan Gregory, an evolutionary biology expert who tracks coronavirus variants, is helpful at putting XBB.1.5 into context. This latest lineage follows other versions of Omicron that have kept the U.S. and other countries at relatively high levels of COVID-19 transmission throughout the last year. While our current moment may not look as dire as January 2022, we are currently seeing COVID-19 go up from an already-unsustainable baseline.

 “BA.1 was the highest peak,” he writes, referring to 2022 in Canada and the U.K., “but the area under the curve of the others was as bad or worse.”

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