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Health Experts Warily Eye XBB.1.5, the Latest Omicron Subvariant


Three years after the pandemic, the coronavirus continues to impress virologists with its rapid evolution.

A young version called XBB.1.5 has gone viral in the US over the past few weeks. since fridayThe Centers for Disease Control estimates that it accounts for 72 percent of new cases in the Northeast and 27.6 percent of cases nationwide.

The new sub-variant, first sampled this fall in New York State, has a series of potent mutations that seem to help it evade the immune system and improve its ability to invade cells.

“This is the most contagious variant that has been detected,” said Maria Van Kerkhove, Covid-19 technical team leader at the World Health Organization.

XBB.1.5 still rare in many parts of the world. But Tom Wenseleers, an evolutionary biologist at KU Leuven in Belgium, expects it to spread quickly and globally. “It is very likely that we will have another wave of infections,” he said.

Advisors at WHO are assessing the risk posed by XBB.1.5. Jacob Lemieux, an infectious disease physician at Massachusetts General Hospital, says the increase in cases won’t equal the first Omicron spike Americans experienced a year ago. “Is it a Category 5 hurricane?” he say. “No.”

However, he cautioned that XBB.1.5 could exacerbate what has already formed a harsh Covid winter, when people gather indoors and do not receive boosters that can prevent serious illness. .

Dr. Ashish K. Jha, the White House’s Covid-19 response coordinator, said the Biden administration was monitoring the arrival of XBB.1.5 and urged everyone to take advantage of existing countermeasures. Preliminary studies show that dichotomous vaccine will provide good protection against XBB and its descendants. Paxlovid will also remain effective in fighting infections.

Dr Jha said: “We feel quite comfortable that our countermeasures will continue to work. “But we have to make sure that people are using them.”

One thing that Dr. Lemieux and other experts are confident about is that XBB.1.5 is not the final chapter in the evolution of the coronavirus. In fact, they hope that the descendants of XBB.1.5 may soon receive mutations that help it propagate even better.

That descendant may already exist, infecting people without notice. But sequencing efforts have been greatly reduced worldwide, so the discovery of the next generation of XBB.1.5 could be delayed. Dr Van Kerkhove said: “As sequencing became less and less available at the global level, it was difficult for us to track each Omicron sub-variant.

Scientists reconstructed the evolution of XBB.1.5 (which some have nicknamed Kraken) by studying the novel coronavirus sequences in an online database. The first major step took place last year when two earlier forms of Omicron infected the same person. As viruses multiply, their genetic material is mixed together. A new hybrid has emerged, with genetic material from both parents of the virus. Virus watchers named it XBB.

this blend, called recombination, occurs fairly frequently between coronaviruses. During the course of the pandemic, scientists have found several recombinant forms of SARS-CoV-2, the cause of Covid-19.

Most recombinant SARS-CoV-2 viruses have weakened over several weeks or months, unable to overcome other strains. On the other hand, XBB won the winning ticket in the genetic lottery. From one parent, it has received a set of mutations that help it ward off antibodies from previous infections and vaccinations. From the other parent, it received a distinct set of mutations that made it even more evasive.

“XBB has really collected the most probable mutations it can collect from those two parents,” said Thomas Peacock, a virologist at Imperial College London. The new combination made XBB one of the most unlikely Omicron sub-variants last summer.

Recent experiments show that XBB has paid a heavy price for its power to evade immunity. The mutations allow it to escape the antibodies by changing the shape of the protein, called spikes, that cover its surface. But some of those mutations also make it harder for the XBB mutant proteins to adhere to the cell – the necessary first step to infection.

That laxity may have reduced XBB’s advantage over other viruses. At the end of 2022, it competes with several other sub-variants of Omicron. In Singapore, for example, XBB caused a spike in October, while still being rare in many other parts of the world.

As XBB multiplies, it continues to transform into new forms. The earliest samples of XBB.1.5 were isolated in October in New York. The new sub-variant gained an important mutation, called F486P.

Yunlong Cao of Peking University and his colleagues tested XBB.1.5 in cell plates, comparing how it performed compared to earlier forms of XBB. The researchers found that the F486P mutation allowed XBB.1.5 to adhere to cells once again. But the new sub-variant can still evade antibodies as well as previous forms of XBB.

Dr. Cao and his colleagues posted online results on Thursday. The data has yet to be published in a scientific journal.

XBB.1.5 most likely developed somewhere in the northeastern United States, where early samples identified for the first time and where it is still most popular. Once scientists can recognize it, they can track its development.

in Connecticut, for example, Nathan Grubaugh at Yale University and his colleagues found that by mid-December, other sub-variables of Omicron were decreasing. Only the XBB.1.5 case is in development. Dr. Grubaugh estimates that it is about 20% more transmissible than BQ.1, the predominant form.

“It doesn’t show signs of a big wave like we’ve seen before,” he said. “It won’t come close to what it was last year.”

The severity of XBB.1.5 infection compared with other forms of coronavirus remains unclear. “It’s serious,” Dr. Grubaugh said. “I just don’t necessarily know if it’s actually more severe than some of the other Omicron lineages in terms of overall impact.”

XBB.1.5 has spread to other countries and is growing rapidly in Germany, Denmark and elsewhere in Europe. But its impact can vary from place to place. In India, for example, it will encounter many people who were infected with its parent’s strain last year, so it may face stronger immunity, Dr Peacock said.

In China, which experienced a major outbreak of cases in late 2022, its outlook is even more difficult to predict. For most of the pandemic, China almost never shared viral sequences with international databases. Cooperation has increased over the past few weeks, but the database 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 resistance to other Omicron subvariants. In China, where there is less immunity, it may not have that advantage. Dr. Peacock speculates that after other variants spread across China, it may be XBB.1.5’s turn to rise.

Dr. Wenseleers said that the spread of XBB.1.5 outside of China made him skeptical that restrictions on Chinese travelers would help reduce cases. “It’s kind of nonsense,” he said. “It would be better to make sure that the elderly are fully vaccinated.”

As XBB.1.5 spreads, it continues to mutate and experts believe it may get better at evading antibodies.

The scientists scanned the newly uploaded sequences to an international database called GISAID in the hopes of discovering an upgraded version of XBB.1.5. But their job is getting harder and harder as governments are pulling back from sequencing efforts. “Worldwide, sequencing has been a real success,” said Dr. Peacock.

The United States, which once lagged behind other countries, has managed to maintain a fairly vigorous sequencing effort. Without it, Dr. Peacock said, XBB.1.5 could have been under the radar much longer. If the next generation of XBB.1.5 is in development somewhere with few sequences, it may go undetected for a while.

Dr Lemieux said that cutting the sequence was a mistake, given how many infections and deaths the virus is still causing. “This is part of public health,” he said.

And Dr. Peacock said that XBB.1.5 proved that the evolution of the coronavirus is not going to slow down any time soon. “Wait two more years, and maybe we can reassess where we think this is,” he said.

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