Happy Birthday, Omicron

On Nov. 26, 2021, the World Health Organization announced that a concerning new variant of the coronavirus, known as Omicron, had been discovered in southern Africa. It soon swept to dominance across the world, causing a record-breaking surge in cases.

Now, a year later, Omicron still has biologists scrambling to keep up with its surprising evolutionary turns. The variant is rapidly gaining mutations. But rather than a single lineage, it has exploded into hundreds, each with resistance to our immune defenses and its own alphanumeric name, like XBB, BQ.1.1 and CH.1.

“It’s hard to remember what is what,” Jesse Bloom, a virologist at the Fred Hutchinson Cancer Center in Seattle, said.

But unless some radically different variant emerges, Dr. Bloom predicted, this confusing jumble of subvariants will endure, making it more challenging for scientists to plan new vaccines and treatments.

“It’s always going to kind of be like it is now,” he said. “There’s always going to be some soup of new variants out there.”

When Omicron emerged last November, it carried more than 50 mutations that set it apart from other variants of the coronavirus. Many researchers favor the idea that it arose in a single person, perhaps with a compromised immune system, who had a chronic case of Covid that lasted months.

Last month, however, a team of scientists at the University of Minnesota suggested that an early form of the coronavirus had infected mice. In their scenario, it evolved into Omicron in the rodents and then infected humans again.

However it arose, Omicron surged to dominance in the weeks after its discovery because of its mutations. Some of them allowed the virus to slip inside cells more successfully. Others let it evade some of the antibodies from vaccines or previous infections.

Most antibodies stick to the “spike” proteins on the surface of coronaviruses, blocking them from entering our cells. But some of Omicron’s mutations changed parts of the spike protein so that some of the most potent antibodies could no longer stick to it.

As Omicron multiplied, it continued to mutate. New versions emerged, but for the first few months they replaced one another like a series of waves crashing on a beach. The first version, BA.1, was replaced by BA.2, then BA.5, both of which evaded some antibodies produced from earlier Omicron infections.

But in February, Theodora Hatziioannou, a virologist at Rockefeller University in New York, and her colleagues ran an experiment that suggested Omicron was primed for an evolutionary explosion.

Dr. Hatziioannou’s team tested Omicron against 40 different antibodies that could still block the variant. They discovered that it was remarkably easy for a few extra mutations to make it resistant to almost all of those antibodies.

Surprisingly, when the researchers added those same mutations to the spike protein from the original version of the coronavirus, there was no effect on its antibody resistance. Dr. Hatziioannou suspected that the large number of new mutations in Omicron changed its evolutionary landscape, making it much easier to evolve even more resistance.

“We were actually worried when we saw this,” she said.

In the months since, Omicron has lived up to those worries. Thanks to the huge number of Omicron infections, the virus has had more opportunity to mutate. And it has gained some of the concerning mutations that Dr. Hatziioannou and her colleagues identified in their experiments.

The new mutations are building up quickly, most likely because they are providing the viruses with a big evolutionary edge. In the first year of the pandemic, most people who were infected had no antibodies for Covid. Now, most people do. So viruses that have extra resistance to antibodies easily outcompete others lacking it.

“The evolution that’s happening is the fastest rate it has been up to this point,” Sergei Pond, a virologist at Temple University in Philadelphia, said.

A single subvariant is not gaining all of the new mutations, however. Ben Murrell, a computational biologist at the Karolinska Institute in Stockholm, and his colleagues are tracking more than 180 Omicron subvariants that have independently gained mutations causing them to grow faster than BA.5.

These subvariants are going through a process that Charles Darwin recognized some 160 years ago, called convergence. Darwin noted how birds and bats independently evolved wings that work very much the same way. Today, Omicron subvariants are independently escaping the same antibodies with mutations at the same spots on their spike proteins.

The competition taking place in the subvariant swarm may be preventing one of them from taking over, at least for now. In the United States, the once-dominant BA.5 now accounts for just 19 percent of new cases. Its descendant BQ.1 has risen to 28 percent. And B.Q.1.1., a descendant of B.Q.1, is the cause of 29 percent. Thirteen other Omicron subvariants make up the rest.

But elsewhere, other subvariants are rising to the top. Singapore, for example, has experienced a surge of XBB, a hybrid of two different subvariants of BA.2. But XBB is rare in most other parts of the world.

“Most of that has just to do with which one seeded an area first,” Thomas Peacock, a virologist at Imperial College London, said.

As each lineage gains more mutations, fewer types of antibodies work against them. Last month, Yunlong Cao, a biochemist at Peking University, and his colleagues reported that XBB and three other subvariants had become entirely resistant to the antibodies in blood samples from people who were vaccinated or had Covid infections.

That development threatens what had been one of the most important defenses against Covid: monoclonal antibodies. To create these treatments, scientists collected blood of Covid patients early in the pandemic, isolated their most potent antibodies, and made vast numbers of copies of the molecules. One formulation, called Evusheld, can prevent people with compromised immune systems from getting infected. But as resistant subvariants become more common, these treatments will no longer work.

“I can’t really be confident whether or not monoclonal antibodies will play a major role in treatment going forward,” Dr. Bloom, of the Fred Hutchinson Cancer Center, said. “It’s going to be really important to design another generation of antibody cocktails that hopefully stand up longer.”

The latest booster shots produce spike proteins from both the original version of the virus and BA.5. Studies on people who have gotten this so-called bivalent booster show that their antibodies are better at neutralizing BQ.1.1 and other new subvariants than the antibodies produced by the original Covid vaccine. Even so, the subvariants can evade many of the bivalent antibodies.

Fortunately, the new subvariants don’t seem to be more deadly than earlier forms of Omicron. Despite their growing ability to evade antibodies, Dr. Hatziioannou said that the subvariants will probably not be able to entirely escape immunity from vaccines or previous infections.

Moritz Gerstung, a computational biologist at the German Cancer Research Center in Heidelberg, said that the lessons scientists were now learning about Omicron’s convergence might allow them to predict its coming evolution. And those predictions, in turn, could allow public health officials to prepare for the next stage of Covid more effectively.

“It has made me very hopeful for the future as a paradigm,” Dr. Gerstung said. “It’s an instance of how one could basically get ahead of the game.”

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