One year after discovery, omicron is rapidly mutating

On November 26, 2021, the WHO (World Health Organization) announced that a worrying new variant of the coronavirus, known as omicron, had been discovered in southern Africa. It soon gained worldwide dominance, causing a record increase in cases.

Now, a year later, biologists are still struggling to keep track of omicron’s surprising evolutionary changes. The variant is rapidly gaining mutations. But instead of a single strain, it has exploded into hundreds, each with resistance to our immune defenses and its own alphanumeric name, such as XBB, BQ.1.1, and CH.1.

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

Unless a radically different variant emerges, Bloom predicted, this confusing mix of subvariants will linger, making it more challenging for scientists to devise new vaccines and treatments. “It will always be the way it is now,” he said. “There will always be a soup of new variants out there.”

When omicron appeared, in November 2021, it carried more than 50 mutations that differentiated it from other variants of the coronavirus. Many researchers support the idea that it originated in a single person, perhaps with a compromised immune system, who had a chronic case of Covid that lasted for 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 to omicron in rodents and then reinfected humans.

Regardless of how it came about, omicron rose to prominence in the weeks after its discovery because of its mutations. Some of them allowed the virus to enter cells more successfully. Others allowed him to escape some antibodies generated by vaccines or previous infections.

Most antibodies stick to the “spike” proteins on the surface of coronaviruses, preventing them from entering our cells. But some omicron mutations modified parts of this protein so that some more potent antibodies could no longer adhere to it.

As the omicron multiplied, it continued to mutate. New versions emerged, but in the first few months they replaced each other like a series of waves crashing onto the beach. The first version, BA.1, was replaced by BA.2, then BA.5, both of which evaded some antibodies produced by previous omicron infections.

In February, Theodora Hatziioannou, a virus expert at The Rockefeller University in New York, and her colleagues performed an experiment that suggested the omicron was ripe for an evolutionary explosion.

Hatziioannou’s team tested the omicron against 40 different antibodies that could still block the variant. They found that it was extremely easy for a few extra mutations to make her resistant to almost all of these antibodies.

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

“We were really concerned when we saw this,” she said.

In the months that followed, omicron overcame these concerns. Thanks to the large number of omicron infections, the virus had more opportunities to mutate. And it gained some of the troubling mutations that Hatziioannou and his colleagues identified in their experiments.

New mutations are developing quickly, probably because they give viruses a huge evolutionary advantage. In the first year of the pandemic, most people infected did not have antibodies to Covid. Now most people have them. Therefore, viruses that have extra antibody resistance easily outperform others that do not.

“The evolution that’s happening is the fastest rate yet,” said Sergei Pond, a virus expert at Temple University in Philadelphia.

However, a single subvariant is not gaining all new mutations. Ben Murrell, a computational biologist at the Karolinska Institute in Stockholm (Sweden), and his colleagues are tracking more than 180 omicron subvariants that have independently mutated, causing them to grow faster than BA.5.

These subvariants are undergoing a process that Charles Darwin recognized about 160 years ago called convergence. Darwin observed how birds and bats independently evolved wings that function the same way. Today, omicron subvariants are independently escaping from the same antibodies with mutations at the same points in their spike proteins.

The competition going on 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 only 19% of new cases. Its descendant BQ.1 rose to 28%. And BQ1.1, a descendant of BQ1, is the cause of 29%. Thirteen other omicron subvariants make up the rest.

As each strain gains mutations, fewer types of antibodies work against it. Last month, Yunlong Cao, a biochemist at Peking University, and his colleagues reported that XBB and three other subvariants became fully resistant to antibodies in blood samples from people vaccinated or with Covid infections.

This development threatens what has been one of the most important defenses against Covid: monoclonal antibodies. To create these treatments, scientists took blood from Covid patients early in the pandemic, isolated their most potent antibodies, and made large numbers of copies of the molecules. One formulation, called Evusheld, may prevent people with compromised immune systems from becoming infected. But as resistant subvariants become more common, these treatments stop working.

“I can’t really be sure whether or not monoclonal antibodies will play an important role in treatment going forward,” said Bloom of the Fred Hutchinson Cancer Center. “It will be very important to design another generation of antibody cocktails that will hopefully last longer.”

The last booster doses produce spike proteins of both the original version of the virus and BA.5. Studies in people given a 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, subvariants can escape many of the bivalent antibodies.

Fortunately, the new subvariants don’t appear to be any more deadly than previous omicron forms. Despite their increasing ability to evade antibodies, subvariants are unlikely to be able to fully evade immunity generated by vaccines or previous infections, Hatziioannou said.

Translated by Luiz Roberto M. Gonçalves.