Omicron variant XBB.1.5 is the most contagious yet

A highly contagious subvariant of Omicron called XBB.1.5 is now the dominant strain spreading in the United States. Early data suggests it’s more evasive than other variants, efficiently dodging previously acquired immunity and raising concerns among public health officials about a possible winter wave.

In December alone, XBB.1.5 grew from causing fewer than 1 percent of confirmed COVID-19 cases nationwide to more than 40 percent, rapidly out-competing other variants. In northeastern states it caused more than 75 percent of all cases for the week beginning December 25, although there is no data yet to indicate whether it causes more severe disease.

“It is the most transmissible subvariant that has been detected yet,” said Maria Van Kerkhove, the technical lead for COVID-19 response at the World Health Organization, during a news conference. Scientists estimate that someone infected with XBB.1.5 can cause 60 percent more infections than a person infected with its parent strains. 

XBB.1.5 was first detected in New York and Connecticut in late October but has since been detected in at least 29 other countries. While it accounts for less than 5 percent of current cases worldwide, it seems to be doubling within eight to 15 days, making it the fastest-spreading SARS-CoV-2 variant to date. In fact, XBB.1.5 might be far more widespread, according to Kerkhove, since it’s difficult to tell as genomic sequencing efforts for monitoring the SARS-CoV-2 have declined around the world.

Where did XBB.1.5 come from?

XBB.1.5 descended from variant XBB.1, which arose from XBB—the fusion of two Omicron BA.2 variants. Its grandparental strain, XBB, and its parental strain XBB.1—responsible for a surge of COVID-19 cases in parts of Asia in October and November 2022—were able to evade immunity conferred by previous infections and the bivalent boosters that were specifically designed to block Omicron variants, according to a report published in Nature in December. In Singapore, XBB subvariants caused a large number of breakthrough infections and reinfections, although hospitalization rates remained low.

How is the new variant different?

The XBB.1.5 variant features a new mutation at the 486 position of the spike, which is the protein the virus uses to bind to the ACE2 receptor protein on cells in the human respiratory tract. Mathematical models predicted that a change in the spike protein at this position would allow a variant to escape previous antibodies. Those predictions seem to be correct.

"The mutation brings higher ACE2 binding while maintaining XBB.1's extremely high immune evasion capability," says Yunlong Cao, of Peking University in China, based on his preliminary research exploring the enhanced contagiousness of XBB.1.5, which is not yet peer reviewed.

Cao’s preliminary research also shows that some monoclonal antibody therapies, such as Evusheld and Bebtelovimab, do not block XBB.1.5, although Sotrovimab provided weak protection.

Does the bivalent booster protect against XBB.1.5?

It’s too early to know how the current bivalent booster—which targets previous Omicron strains BA.4 and BA.5, as well as the original coronavirus would protect against XBB.1.5. However, recent research on the parental strains of XBB.1.5 led by Mehul Suthar, an immunologist at Emory University School of Medicine, shows that people who got the bivalent booster, as well as those who were recently infected with an Omicron variant, had slightly higher levels of protective antibodies.

"Bivalent boosters seem to be working the way they are supposed to," says Suthar, by shifting our immunity towards Omicron variants. He speculates that the bivalent booster would provide some protection against XBB.1.5, based on its similarity to other Omicron variants. But his research also suggests that even the bivalent booster may not block XBB.1.5 breakthrough infections.

The Centers for Disease Control and Prevention estimates that bivalent boosters reduced COVID-19 hospitalizations by more than 90 percent through November, which is the latest data available. This means even if the boosters may not prevent infections, they may still save lives.

"It is difficult to say anything about pathogenicity of XBB.1.5 yet," says Kei Sato, a virologist at the University of Tokyo, since there are no data yet. However, Sato's preliminary work, not yet peer reviewed, on parent strain XBB has shown that the virus attaches more tightly to human cells than other Omicron variants, such as BA.2.75 and BA.2, which suggests it might cause more severe disease. But when hamsters were infected with XBB, the disease symptoms were no worse than those caused by BA.2.75. "We do not have any ideas explaining this discrepancy yet," says Sato.

Will XBB.1.5 drag out the pandemic?

Hospitalizations due to COVID-19 have risen by 17 percent in the last week, according to the latest CDC data, leading scientists to worry that even without causing more serious disease, a highly contagious XBB.1.5 could worsen the course of the now three-year-long pandemic. Large number of COVID-19 cases can still overwhelm hospitals, where resources are already stretched thin with the high number of RSV and flu respiratory infections.

People ages 65 and older are the most vulnerable to the complications due to COVID-19. Yet, just slightly more than a third of these Americans have received the bivalent booster, leaving them vulnerable to XBB.1.5. When it comes to the U.S. population, nearly 85 percent of those eligible have not received the bivalent shot.

"When infections are high, many people will be affected," says Marc Veldhoen, an immunologist at the Institute of Molecular Medicine in Lisbon, Portugal. "More infections hold more risk, more likelihood of symptoms, and unfortunately, high circulation means many vulnerable [people] will be infected and we will see more people in hospitals."