Health experts are cautiously eyeing XBB.1.5, the latest Omicron subvariant
Three years after the pandemic began, the coronavirus continues to impress virologists with its rapid evolution.
A young version called XBB.1.5 has spread rapidly in the United States in the past few weeks. On Friday, the Centers for Disease Control estimated it accounted for 72 percent of new cases in the Northeast and 27.6 percent of cases nationwide.
The new subvariant, which was first tested in upstate New York this fall, has a potent array of mutations that appear to help it evade immune defenses and improve its ability to enter cells.
“It’s the most transmissible variant discovered so far,” Maria Van Kerkhove, the World Health Organization’s Covid-19 technical lead, said at a news conference on Wednesday.
XBB.1.5 remains rare in much of the world. But Tom Wenseleers, an evolutionary biologist at KU Leuven in Belgium, expects it to spread quickly and globally. “We will most likely have another wave of infections,” he said.
WHO advisers assess 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 five hurricane?” he said. “No.”
Still, he warned that XBB.1.5 could exacerbate the already harsh Covid winter as people congregate indoors and not receive boosters that can ward off serious illnesses.
dr Ashish K. Jha, the White House Covid-19 response coordinator, said the Biden administration is monitoring the emergence of XBB.1.5 and is urging people to use existing countermeasures. Preliminary studies suggest that bivalent vaccines should provide adequate protection against XBB and its progeny. Paxlovid will also remain effective in fighting infections.
“We feel pretty confident that our countermeasures will continue to work,” said Dr. yeah “But we have to make sure people use them.”
One thing that Dr. What Lemieux and other experts are convinced of is that XBB.1.5 is not the last chapter in the development of the coronavirus. In fact, they anticipate that a descendant of XBB.1.5 may soon acquire mutations that will make it spread even better.
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This offspring can already exist and infect humans without it being noticed. But sequencing efforts around the world have dwindled so much that the discovery of the next-generation XBB.1.5 could be delayed. “As sequencing becomes less available on a global scale, it is difficult for us to track each of the Omicron subvariants,” said Dr. Van Kerkhove.
Scientists have reconstructed the evolution of XBB.1.5 (dubbed by some as Kraken) by poring over new sequences of coronaviruses in online databases. The first big step came last year when two previous forms of Omicron infected the same person. As the viruses replicated, their genetic material was shuffled together. A new hybrid form emerged with genetic material from both virus parents. Virus watchers called it XBB.
This mixing, called recombination, is fairly common in coronaviruses. During the course of the pandemic, scientists have found a number of recombinant forms of SARS-CoV-2, the causative agent of Covid-19.
Most recombinant SARS-CoV-2 viruses disappeared within a few weeks or months and have not been able to outperform other lineages. XBB, on the other hand, got a winning ticket in the genetic lottery. It received a series of mutations from a parent that helped it evade antibodies from previous infections and vaccinations. It received a separate set of mutations from the other parent, making it even more evasive.
“XBB literally picked up most of the possible mutations it could possibly pick up from either of these parents,” said Thomas Peacock, a virologist at Imperial College London. The new combo made XBB one of the most evasive Omicron subvariants last summer.
Recent experiments suggest XBB paid a heavy price for its ability to evade immunity. The mutations allow it to evade antibodies by changing the shape of the protein, called spike, that covers its surface. However, some of these mutations also make it harder for the XBB spike proteins to attach tightly to cells — the first step required for infection.
This loose grip may have reduced XBB’s advantage over other forms of the virus. In late 2022, it crowded alongside a number of other Omicron subvariants. For example, in Singapore, XBB caused a surge in October while remaining rare in many other parts of the world.
As XBB reproduced, it continued to mutate into new forms. The first samples of XBB.1.5 were isolated in New York in October. The new subvariant received a crucial mutation known as F486P.
Beijing University’s Yunlong Cao and colleagues tested XBB.1.5 in cell cultures and compared how it performed with previous forms of XBB. The researchers found that the F486P mutation allowed XBB.1.5 to re-attach itself tightly to cells. But the new subvariant was still able to evade antibodies as well as earlier forms of XBB.
dr Cao and his colleagues posted their findings online on Thursday. The data have not yet been published in a scientific journal.
XBB.1.5 most likely evolved somewhere in the Northeastern United States, where early samples were first identified and where it is most common. Once scientists could spot it, they could track its growth.
In Connecticut, for example, Nathan Grubaugh of Yale University and his colleagues found that other omicron subvariants fell in mid-December. Only XBB.1.5 cases increased. dr Grubaugh estimates that it is about 20 percent more transferable than BQ.1, which was the dominant form.
“It doesn’t have those signs of a really big wave like we’ve seen before,” he said. “It won’t be anywhere near what it was last year.”
How severe XBB.1.5 infections are compared to other forms of the coronavirus is not yet clear. “It’s serious,” said Dr. Grubaugh. “I just don’t necessarily know if it’s really more serious than some of the other Omicron lines in terms of overall effects.”
XBB.1.5 has already spread to other countries and is growing rapidly in Germany, Denmark and elsewhere in Europe. But its effects are likely to vary from place to place. In India, for example, it will encounter many people infected with its parent strains last year, so it could face stronger immunity, said Dr. Peacock.
In China, which saw a large spike in cases in late 2022, the outlook is even harder to predict. For most of the pandemic, China has almost never shared virus sequences with international databases. Cooperation has increased in recent weeks, but the databases may still not reflect the state of affairs in the country.
Much of XBB.1.5’s advantage in the United States stems from its ability to bypass existing immunities, including those directed against other Omicron subvariants. In China, where there is less immunity, it may not have that advantage. dr Peacock speculated that it could be XBB.1.5’s turn after the proliferation of other variants in China.
dr 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 ensure that older people are well vaccinated.”
As XBB.1.5 spreads, it continues to mutate, and experts believe it may get even better at evading antibodies.
Scientists are already scanning new sequences that will be uploaded to an international database called GISAID in hopes of discovering an updated version of XBB.1.5. But their job is becoming more difficult as governments pull back on sequencing efforts. “Globally, sequencing has had real success,” said Dr. Peacock.
The United States, once lagging behind other nations, has managed to sustain a fairly strong sequencing effort. Without them, according to Dr. Peacock, XBB.1.5 might have stayed under the radar for a lot longer. If the next generation of XBB.1.5 develops in a place with little sequencing, it may go undetected for some time.
dr Lemieux said it was a mistake to limit sequencing given how many infections and deaths the virus still causes. “This is part of public health,” he said.
and dr Peacock said that XBB.1.5 showed that the development of the coronavirus is not going to slow down any time soon. “Give it another two years and maybe we can reassess where we think that’s the case,” he said.
