The CDC estimates that XBB.1.5 is the second most common variant in the United States, comprising 28% of cases nationally, and upwards of 70% in the northeast (see ‘New year, new variant‘). Moritz Gerstung, a computational biologist at the German Cancer Research Centre in Heidelberg, estimates that cases of the variant are doubling roughly every week in the United States, and a bit more slowly in other countries where the variant has appeared. That’s comparable to the rate at which the BQ.1 and BQ.1.1 variants grew in September 2022, but slower than earlier Omicron waves. “XBB.1.5’s spread is still impressively fast,” Gerstung says.

What’s not clear is whether such growth will be sustained or whether the variant will drive up infections significantly, Gerstung adds. BQ.1 and BQ.1.1 looked set to drive sizeable waves, only to run out of steam in Europe and North America. If the same thing happens with XBB.1.5, the lineage could wind up silently replacing other variants in some countries without causing a big rise in cases.

Big-city variant

Jennifer Surtees, a biochemist at the University at Buffalo in New York, wonders whether researchers are overestimating XBB.1.5’s growth in the Northeastern United States. The variant has become more common in the western New York sequences her team handles, but she hasn’t yet noticed the meteoric rise in XBB.1.5 genomes that labs in New York City are recording.

Gauging XBB.1.5’s impact might not be straightforward, owing to the drop-off in testing for COVID-19, Surtees adds. “I think that we are truly flying blind right now. We have no idea how many cases are really out there.”

Tulio de Oliveira, a bioinformatician at Stellenbosch University in South Africa, thinks researchers should look at hospital cases and other measures of disease severity to best measure XBB.1.5’s impact. Factors such as a cold snap in the Northeastern United States and holiday gatherings could partly explain the variant’s apparent surge, he says. “I think that many scientists are jumping to conclusions and predictions very early and with very little data.”

Evasion expert

One thing that researchers can agree on is that XBB.1.5, like its predecessor XBB, is a master of immune evasion. It carries numerous spike mutations that blunt the potency of antibodies raised by vaccination and infection — including earlier Omicron strains. Bivalent vaccines boost levels of antibodies capable of blocking XBB infection (and probably XBB.1.5) in lab tests2,3, but not by much, notes Cao.

Throughout 2022, researchers including Cao watched Omicron lineages pick up a succession of antibody-evading mutations in the viral spike protein that allowed new lineages to overcome immunity gained from vaccines and previous waves. XBB.1.5 is vastly more transmissible than other circulating variants thanks to the addition of the F486P mutation, so there is currently little evolutionary pressure on the lineage to change further, says Cao.

But as global immunity to the subvariant builds, XBB.1.5 won’t stand still, he says. “We are going to see a lot of new mutations that we have never seen before.”