The Omicron family of SARS-CoV-2, the virus that causes COVID, has some new menacing members. At the end of the week ending October 29, data from the U.S. Centers for Disease Control and Prevention showed that two variants—BQ.1 and BQ.1.1—account for nearly 17 percent of viral samples genetically sequenced in the country. That was a huge increase over a month earlier when the variants were practically invisible in the data and suggests they will soon outcompete BA.5 and BA.4.6, the dominant strains in the United States. Meanwhile, a variant called XBB has been causing a substantial infection wave in Southeast Asia.

The three new variants are likely spreading so quickly because they sneak past some of the immune defenses acquired through previous infections and vaccinations. They also threaten to render monoclonal antibody treatments ineffective. These features warrant attention—especially as the country heads into the fall and winter—but not panic. Scientists suspect that the COVID vaccines will continue to protect against hospitalization and death. And Paxlovid, an oral antiviral pill, is also expected to remain effective. The mixed news means that the variants “have the ability to create a wave, but it’s not going to be a tsunami,” says Katelyn Jetelina, an epidemiologist at UTHealth and publisher of the “Your Local Epidemiologist” newsletter.  

Omicron first emerged near the end of last year. The initial version known as BA.1 (previously known as B.1.1.539) overtook the Delta variant and caused more than 800,000 U.S. cases per day during its January peak. But BA.1 was just the first in a long line of Omicron subvariants. BA.2 took over from BA.1 and caused a surge in the spring. BA.5 edged out BA.2 and caused a surge in the summer. And now it looks like BQ.1, BQ.1.1, XBB—or some combination—will cause a surge this fall and winter. For the record: BQ.1.1 is the same as BQ.1 but with an additional mutation. So many scientists think the race will occur between BQ.1 or BQ.1.1 and XBB. But just how that race plays out—and whether it will cause a surge—depends on three essential metrics: how quickly these variants spread; if they cause more severe disease; and if they can circumvent our immune protection or evade immune-focused treatments.

There is no question these variants are increasing at a rapid rate. BQ.1.1, for example, currently accounts for 7,000 cases per day and appears to be doubling every nine days, says Trevor Bedford, a virologist at the Fred Hutchinson Cancer Center who models COVID evolution. It is outpacing BA.5—the current leading variant in the U.S. That’s because every person sick with BQ.1.1 is infecting an average of 1.4 other people, while those sick with BA.5 are averaging an infection of less than one other person. This so-called reproduction number can be telling. When BA.1 first arose, for example, it had a whopping reproduction number of 3. And when BA.5 first arose, it had a reproduction number of 1.6—roughly akin to that for BQ.1.1 and XBB. Barring the appearance of a totally new variant, the U.S. will likely see a wave similar to BA.5’s surge earlier this summer, but nothing on the scale of the Omicron surge last winter, Bedford says. And while it is too soon to tell whether BQ.1.1 or XBB will drive a larger fraction of infections, he predicts two likely scenarios: either BQ.1.1 hits first and suppresses the circulation of XBB (which has already been detected in the U.S. but is not yet widely circulating), or they cause two simultaneous waves. Depending on what comes into play, Bedford predicts the U.S. will see 100,000 to 200,000 COVID cases per day—much higher than today’s average of fewer than 40,000 cases per day.

But how the number of cases will translate to hospitalizations and deaths is a big question. BQ.1, BQ.1.1 and XBB all carry mutations in the spike protein—the studs on the pathogen’s surface that it uses to recognize and infect cells. These mutations make it harder for the immune system to recognize the virus and kick into action early. Indeed, a few preliminary studies (neither of which have been peer-reviewed) have shown that antibodies from vaccination and earlier infections are less able to block infection from these new variants in a lab dish. That sounds scary, but our immune response includes additional levels of defense beyond antibodies, such as T cells and B cells. “These laboratory tests give us a really powerful and important data point—but they don't tell the whole story,” says Justin Lessler, an epidemiologist at the University of North Carolina Gillings School of Global Public Health. So while the likelihood of reinfections will increase with the new subvariants, it will not necessarily drive more severe disease.

To answer that question, scientists marry lab data with real-world data. Hospitalizations appear to be increasing in Germany, but scientists cannot say if that is a result of BQ.1.1 or behavioral changes since Oktoberfest just occurred. The same is true in New York, which has the highest proportion of BQ.1.1 and an uptick in hospitalizations. But again, that could be driven by behavioral changes as the weather cools and children are back in school. And scientists are hopeful that the vaccines will continue to work well against the new variants. The reason scientists chose a bivalent booster, which targets both the original strain and the currently circulating strains BA.4 and BA.5, is that it would provide a broader immune response to current and future variants. “The whole theory behind the bivalent booster is to protect against exactly this situation here, which is the rapid evolution of SARS-Cov-2,” says Sam Scarpino, a viral surveillance expert at the Rockefeller Foundation’s Pandemic Prevention Initiative.

Another tool used to combat infection is a greater cause for concern. These new variants threaten to disarm monoclonal antibody treatments, such as Evusheld, which have played an important role in protecting immunocompromised people and others at high risk of serious disease. But they work by targeting a specific shape on the virus and that shape has simply mutated. “Unfortunately, that means a lot of our tools to protect the most vulnerable in our population continue to be stripped away,” Jetelina says. Luckily, Paxlovid—which has proved effective at preventing serious cases of the disease, particularly in older populations—does not target a specific shape on the virus, and should continue to work well, Jetelina says.

All of this means that the new variants will likely exacerbate the expected fall and winter surge. That’s particularly worrisome when pediatric hospitals are overflowing with respiratory syncytial virus (RSV), influenza is ticking up and there are very few mitigation measures in place. And while the booster vaccine is expected to still do a good job of keeping people safe from severe infection, hospitalization and death, enthusiasm for it is low. As of late October, only about 20 million people in the U.S. had received the updated bivalent shot—roughly 8 percent of the eligible population. “The time for people to take action both for flu vaccines and for the bivalent booster is now,” Scarpino says. “I wouldn't wait.”

Scientists are also recommending dusting off those N95 or other high-quality masks, opening the windows at large gatherings and taking advantage of rapid tests—especially if you are going to see someone who is at high risk of severe disease. “I think everyone really needs to be laser focused this winter on protecting the vulnerable,” Jetelina says. If we can do that, she says, it will save lives and immensely reduce the pressure on our fragile health care system.