Three years after the pandemic, the coronavirus continues to amaze virologists with its rapid evolution.
A new version, known as XBB.1.5, has spread rapidly across the United States in recent weeks. From Fridaythe Centers for Disease Control estimated that they account for 72 percent of new cases in the Northeast and 27.6 percent of cases nationwide.
The new subvariant, first obtained this fall in New York State, has a powerful set of mutations that appear to help it evade immune defenses and improve its ability to invade cells.
“It is the most contagious variant detected to date,” Maria Van Kerkove, the World Health Organization's technical lead for Covid-19, told 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're going to have another wave of infection, probably,” he said.
WHO consultants assess the risk of XBB.1.5. Jacob Lemieux, an infectious disease physician at Massachusetts General Hospital, said the increase in cases will not match the first spike in Omicron that Americans experienced a year ago. “Is it a category five hurricane?” he said. “No.”
But he warned that XBB.1.5 could worsen what is already shaping up to be a harsh Covid winter as people huddle indoors and don't get boosters that can prevent serious illness.
Dr. Ashish K. Jha, the White House coordinator for the response to Covid-19, said the Biden administration was monitoring the emergence of XBB.1.5 and urging people to take advantage of existing countermeasures. Preliminary studies show that bivalent vaccines it should provide decent protection against XBB and its progeny. Paxlovid will also remain effective in fighting infections.
“We feel very comfortable that our countermeasures will continue to work,” Dr. Ja said. “But we have to make sure people use them.”
One thing Dr. Lemieux and other experts are sure of is that XBB.1.5 is not the last chapter in the evolution of the coronavirus. In fact, they expect that a descendant of XBB.1.5 may soon acquire mutations that will make it even better at propagating.
This progeny may already exist, infecting humans without yet being notified. But sequencing efforts have fallen so far worldwide that 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 each of the Omicron sub-variants,” said Dr Van Kerkhove.
Scientists have reconstructed the evolution of XBB.1.5 (which some have dubbed the Kraken) by examining new coronavirus sequences in online databases. The first major step came last year when two earlier forms of Omicron infected the same person. As the viruses replicated, their genetic material mixed together. A new hybrid form emerged, with genetic material from both parent viruses. Virus watchers called it XBB.
This mixing, called recombination, happens quite often between coronaviruses. During the pandemic, scientists have found a number of recombinant forms of SARS-CoV-2, the cause of Covid-19.
Most recombinant SARS-CoV-2 viruses have disappeared within weeks or months, unable to compete with other lineages. XBB, on the other hand, got a winning ticket in the genetic lottery. From one parent, it acquired a set of mutations that helped it avoid antibodies from previous infections and vaccinations. From the other parent, it acquired a separate set of mutations that made it even more evasive.
“XBB literally got the most possible mutations it could possibly get from those two parents,” said Thomas Peacock, a virologist at Imperial College London. The new combination made XBB one of the most elusive Omicron subvariants around last summer.
Recent experiments show that XBB paid a heavy price for its power to evade immunity. The mutations allow it to escape antibodies by changing the shape of the protein, called a spike, that covers its surface. But some of these mutations also make it harder for the XBB spike proteins to latch onto cells—the first step required for an infection.
This loose grip may have reduced XBB's advantage over other forms of the virus. In late 2022, it moved along with a number of other Omicron sub-variants. In Singapore, XBB caused a surge in October, for example, while remaining rare in many other parts of the world.
As XBB proliferated, it continued to mutate into new forms. The first samples of XBB.1.5 were isolated in October in New York. The new subvariant acquired a critical mutation known as F486P.
Yunlong Cao of Peking University and colleagues tested XBB.1.5 in cell discs, comparing its course with previous forms of XBB. The researchers found that the F486P mutation allowed XBB.1.5 to cling tightly to cells again. But the new subvariant could still evade antibodies as well as previous forms of XBB.
Dr. Cao and his colleagues published theirs results online on Thursday. The data have not yet been published in a scientific journal.
XBB.1.5 likely evolved somewhere in the northeastern United States, where the first samples were detected for the first time and where it remains most common. Once scientists could identify it, they could track its growth.
In ConnecticutFor example, Nathan Grubaugh at Yale University and his colleagues found that by mid-December, other subvariants of Omicron were falling. Only XBB.1.5 instances were increasing. Dr. Grubaugh estimates that it is about 20 percent more contagious than BQ.1, which was the dominant form.
“It doesn't have these signs of a really big wave like we've seen before,” he said. “It's not going to be anywhere near what it was last year.”
How severe XBB.1.5 infections compare to other forms of the coronavirus is not yet clear. “It's serious,” said Dr. Grubo. “I just don't necessarily know if it's really more severe than some of the other Omicron lineages in terms of overall impact.”
XBB.1.5 has already spread to other countries and is growing rapidly in Germany, Denmark and elsewhere in Europe. But its impact is likely to vary from place to place. In India, for example, it will encounter many people infected by its parent strains last year, so it may face stronger immunity, Dr. Peacock said.
In China, which experienced a large increase in cases in late 2022, its outlook is even more difficult to predict. For 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 United States comes from its ability to evade existing immunity, including that against other Omicron subvariants. In China, where there is less immunity, it may not have this advantage. Dr. Peacock speculated that after other variants spread in China, it might be XBB.1.5's turn to go up.
Dr Wenseleers said the spread of XBB.1.5 outside of China made him doubtful that restrictions on Chinese travelers would reduce cases. “It's kind of pointless,” he said. “We'd better make sure 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 hoping to locate an upgraded version of XBB.1.5. But their job is getting harder because governments are pulling back from sequencing efforts. “Around the world, sequencing has taken a real hit,” Dr Peacock said.
The United States, once lagging behind other nations, has managed to maintain a fairly strong sequencing effort. Without it, Dr Peacock said, XBB.1.5 could have remained under the radar for much longer. If the next generation of XBB.1.5 is being developed somewhere out of sequence, it may go unnoticed for quite some time.
Dr. Lemieux said the sequencing review was a mistake given how many infections and deaths the virus continues to cause. “This is part of public health,” he said.
And Dr Peacock said XBB.1.5 showed the evolution of the coronavirus would not be slowing down anytime soon. “Give it another couple of years and maybe we can reassess where we think this is,” he said.
