Three years into the pandemic, the coronavirus continues to impress virus experts with its rapid evolution.
A young version, known as XBB.1.5, has spread rapidly in the United States in recent weeks. As of Friday, the Centers for Disease Control and Prevention estimated it accounted for 72% of new cases in the Northeast and 27.6% of cases nationwide.
The new subvariant, first sampled this fall in New York state, has a potent array of mutations that appear to help it evade immune defenses and improve its ability to invade cells.
“It is the most transmissible variant that has been detected so far,” Maria Van Kerkhove, COVID-19 technical lead at the World Health Organization, said at a news conference on Wednesday.
XBB.1.5 is still rare in much of the world. But Tom Wenseleers, an evolutionary biologist at KU Leuven in Belgium, expects it to spread quickly and globally. “Most likely we will have another wave of infections,” he said.
WHO advisers are evaluating the risk posed by XBB.1.5. Jacob Lemieux, an infectious disease physician at Massachusetts General Hospital, said the rise in cases would not match the first omicron spike Americans experienced a year ago. “Is it a category 5 hurricane?” he said. “Not.”
Still, he warned that XBB.1.5 could worsen what is already shaping up to be a harsh COVID winter as people gather indoors and don’t get backup that could prevent serious illness.
Dr. Ashish Jha, the White House COVID response coordinator, said the Biden administration was monitoring the emergence of XBB.1.5 and urging people to take advantage of existing countermeasures. Preliminary studies suggest that bivalent vaccines should provide decent protection against XBB and its descendants. Paxlovid will also continue to be effective in fighting infections.
“We feel quite comfortable that our countermeasures will continue to work,” Jha said. “But we have to make sure that people are using them.”
One thing that Lemieux and other experts are confident is that XBB.1.5 is not the last chapter in the evolution of the coronavirus. In fact, they hope that a descendant of XBB.1.5 will soon get mutations that make it even better at propagating.
That offspring may already exist, infecting people without being reported yet. But sequencing efforts have slowed down so much around the world that the discovery of the next generation of XBB.1.5 may be delayed. “As sequencing becomes less and less available globally, it is difficult for us to track down every single omicron subvariant,” Van Kerkhove said.
Scientists have pieced together the evolution of XBB.1.5 (nicknamed the Kraken by some) by poring over new coronavirus sequences in online databases. The first big step came last year when two earlier forms of omicron infected the same person. As viruses replicated, their genetic material got mixed up. A new hybrid form emerged, with genetic material from both viral parents. Virus watchers called it XBB.
This mixing, called recombination, occurs quite frequently among coronaviruses. Over the course of the pandemic, scientists have found several recombinant forms of SARS-CoV-2, the cause of COVID.
Most recombinant SARS-CoV-2 viruses have declined in a matter of weeks or months, unable to compete with other lineages. XBB, on the other hand, got a winning ticket in the genetic lottery. From one of his parents, he got a set of mutations that helped him evade antibodies from previous infections and vaccinations. From the other parent, he got a separate set of mutations that made him even more elusive.
“XBB literally picked up as many possible mutations as it could get from those two parents,” said Thomas Peacock, a virus expert at Imperial College London. The new combination made XBB one of the most elusive omicron subvariants out there last summer.
Recent experiments suggest that XBB paid a heavy price for its power to evade immunity. The mutations allow it to escape antibodies by altering the shape of the protein, called a spike, that covers its surface. But some of those mutations also make it difficult for the XBB spike proteins to adhere tightly to cells, the first step required for an infection.
That loose control may have diminished XBB’s advantage against other forms of the virus. In late 2022, it was pushed alongside other omicron sub-variants. In Singapore, XBB triggered a spike in October, for example, while it remains rare in many other parts of the world.
As XBB multiplied, it continued to mutate into new forms. The first samples of XBB.1.5 were isolated in October in New York. The new subvariant gained a crucial mutation, known as F486P.
Yunlong Cao of Peking University and colleagues tested XBB.1.5 in cell dishes, comparing how it fared with earlier forms of XBB. The researchers found that the F486P mutation allowed XBB.1.5 to once again take a tight hold on cells. But the new subvariant could still evade antibodies as well as earlier forms of XBB.
Cao and his colleagues posted their results online on Thursday. The data has not yet been published in a scientific journal.
XBB.1.5 most likely evolved somewhere in the northeastern United States, where the first samples were identified and where it remains most common. Once scientists could recognize it, they could track its growth.
In Connecticut, for example, Nathan Grubaugh of Yale University and his colleagues found that, by mid-December, other subvariants of the omicron were crashing. Only the XBB.1.5 cases were growing. Grubaugh estimates that it is 20% more transmissible than BQ.1, which had been the dominant form.
“It doesn’t have those signs of a really big wave like we saw before,” he said. “It won’t come close to what it was last year.”
It is not yet clear how serious XBB.1.5 infections are compared to other forms of the coronavirus. “It’s serious,” Grubaugh said. “I just don’t necessarily know if it’s really more serious than some of the other omicron lineages in terms of the overall impact.”
XBB.1.5 has already spread to other countries and is growing rapidly in Germany, Denmark, and other parts of Europe. But its impact is likely to differ from place to place. In India, for example, you’ll find many people who got infected with their parental strains last year, so you may face stronger immunity, Peacock said.
In China, which experienced a large increase in cases at the end of 2022, its prospects are even more difficult to predict. During most of the pandemic, China almost never shared virus sequences with international databases. Cooperation has increased in recent weeks, but the databases may not yet reflect the situation in the country.
Much of XBB.1.5’s advantage in the US comes from its ability to evade existing immunity, including that against other omicron sub-variants. In China, where there is less immunity, you may not have that advantage. Peacock speculated that after other variants spread across China, it might be XBB.1.5’s turn to ramp up.
Wenseleers said the spread of XBB.1.5 outside of China made him skeptical that restrictions on Chinese travelers would keep cases down. “It’s kind of pointless,” he said. “It would be better to make sure that the elderly are well vaccinated.”
As XBB.1.5 spreads, it continues to mutate, and experts believe it may become even better at evading antibodies.
Scientists are already scanning new sequences that are uploaded to an international database called GISAID in the hope of detecting an improved version of XBB.1.5. But their job is getting harder because governments are backing down on sequencing efforts. “Throughout the world, sequencing has been extremely successful,” Peacock said.
The United States, once lagging behind other nations, has managed to maintain a fairly strong sequencing effort. Without it, Peacock said, XBB.1.5 might have stayed under the radar for much longer. If the next generation of XBB.1.5 is evolving somewhere with little sequence, it may go unnoticed for some time.
Lemieux said reducing sequencing was a mistake, given the number of infections and deaths the virus is still causing. “This is part of public health,” she said.
And Peacock said that XBB.1.5 demonstrated that the evolution of the coronavirus would not slow down any time soon. “Give it another two years, and maybe we can reassess where we think it is,” he said.