As Omicron Rages, Scientists Have No Idea What Comes Next |  Science

As Omicron Rages, Scientists Have No Idea What Comes Next | Science

In the short history of the COVID-19 pandemic, 2021 was the year of new variants. Alpha, Beta, Gamma, and Delta each had a couple of months in the sun.

But this was the year of Omicron, which swept the world in late 2021 and continued to dominate, with subvariants, given more prosaic names like BA.1, BA.2 and BA.2.12.1 , which appear in rapid succession. Two closely related sub-variants called BA.4 and BA.5 are now driving infections around the world, but new candidates, including one called BA.2.75, are knocking on the door.

Omicron’s enduring dominance has led evolutionary biologists to wonder what comes next. Some think it’s a sign that the initial evolution frenzy of SARS-CoV-2 is over and, like other coronaviruses that have been with humanity much longer, is settling into a gradual evolution pattern. “I think a good guess is that BA.2 or BA.5 will generate additional offspring with more mutations and that one or more of these subvariants will spread and be the next thing,” says Jesse Bloom, an evolutionary biologist at the Research Center. Fred Hutchinson cancer.

But others believe that a new variant different enough from Omicron and all other variants to warrant the next Greek letter designation, Pi, may already be developing, perhaps in a chronically infected patient. And even if Omicron is not replaced, his domination is no cause for complacency, says Maria Van Kerkhove, technical manager for COVID-19 at the World Health Organization. “It’s bad enough the way it is,” she says. “If we can’t get people to act [without] a new Greek name, that’s a problem.

Even with Omicron, Van Kerkhove points out, the world may face continuous waves of disease as immunity wanes and new subvariants arise. She is also alarmed that the surveillance efforts that have allowed researchers to detect Omicron and other new variants early are decreasing or slowing. “Those systems are being dismantled, they are being defined, people are being fired,” she says.

The variants that ruled in 2021 did not arise from each other. Instead, they evolved in parallel from the SARS-CoV-2 viruses that circulated at the start of the pandemic. In viral family trees, researchers draw to visualize the evolutionary relationships of SARS-CoV-2 viruses, these variants appeared at the tips of long, bare branches. The pattern appears to reflect the virus lurking in a single person for a long time and evolving before it emerges and spreads again, much changed.

More and more studies seem to confirm that this occurs in immunocompromised people who cannot eliminate the virus and have long-lasting infections. On July 2, for example, Yale University genomic epidemiologist Nathan Grubaugh and his team posted a medRxiv preprint on one such patient they accidentally found. In the summer of 2021, their surveillance program at Yale New Haven Hospital continued to find a variant of SARS-CoV-2 called B.1.517 even though that lineage was supposed to have disappeared from the community long ago. It turned out that all of the samples were from the same person, an immunocompromised patient in his 60s undergoing treatment for a B-cell lymphoma. He was infected with B.1.517 in November 2020 and is still positive today.

Making waves

A number of Omicron subvariants have appeared in rapid succession around the world since the beginning of this year. Some scientists say the model will likely continue, but an entirely new variant may still arise.

Omicron sub-variant infection chart in 2022
(Graphic) C. Bickel and N. Desai /Science; (Data) Nextstrain / GISAID

Following his infection to observe how the virus changed over time, the team found that it evolved at twice the normal rate of SARS-CoV-2. (Some of the viruses circulating in the patient today could be qualified as new variants if they were found in the community, says Grubaugh.) This supports the hypothesis that chronic infections could drive the “unpredictable emergence” of new variants, the researchers write. their prepress.

Other viruses that chronically infect patients also change faster within a host than when they spread from one person to another, says Aris Katzourakis, an evolutionary biologist at Oxford University. This is partly a numbers game: there are millions of viruses replicating in an individual, but only a handful are transmitted during transmission. So much potential evolution is lost in a chain of infections, while a chronic infection offers endless opportunities for evolution.

But since Omicron emerged in November 2021, no new variants have appeared out of thin air. Instead, Omicron has accumulated small changes, making it more effective in evading immune responses and, along with waning immunity, leading to successive waves. “I think it’s probably getting harder and harder for these new things to emerge and take over because all the different Omicron lineages are stiff competition,” says Grubaugh, given how transmissible and immunizing they are already.

If so, the US decision to update COVID-19 vaccines by adding an Omicron component is the right move, Bloom says; even as Omicron continues to change, a vaccine based on it is likely to provide more protection than one based on previous variants.

But it is still possible that a completely new variant unrelated to Omicron will emerge. Or one of the earlier variants, such as Alpha or Delta, could return after causing a chronic infection and going through a period of accelerated evolution, says Tom Peacock, a virologist at Imperial College London: “This is what we would call second generation variants. Given these possibilities, “The study of chronic infections is now more important than ever,” says Ravindra Gupta, a microbiologist at the University of Cambridge. “They could tell us the kind of mutational direction the virus will take in the population.”

BA.2.75, which was recently revived, has already interested some scientists. Dubbed Centaurus, it evolved from Omicron but appears to have rapidly amassed a whole host of major changes in its genome, more like an entirely new variant than a new sub-variant of Omicron. “It looks exactly like Alpha, or Gamma or Beta,” says Peacock.

BA.2.75 appears to be spreading to India, where it was first identified, and has been found in many other countries. It is unclear whether it is really overtaking other sub-variants, Van Kerkhove says, “The data is super-limited right now.” “I definitely think it’s worth keeping an eye on,” says Emma Hodcroft, a virologist at the University of Bern.

Keeping an eye on anything is becoming more and more difficult, as surveillance is decreasing. Switzerland, for example, now sequences about 500 samples per week, down from 2,000 at its peak, says Hodcroft; the United States went from more than 60,000 per week in January to around 10,000. “Some governments are eager to cut back on the money they put into sequencing,” says Hodcroft. Defending spending is a “hard sell,” she says, “especially if there is a sense that the countries around you will continue to sequence even if you stop.”

Even if a variant emerges in a location with good surveillance, it may be more difficult than in the past to predict how large a threat is, because the differences between past waves of COVID-19, vaccines and immunization programs have created a global chessboard. of immunity. This means that a new variant might be fine in one place but run into a wall of immunity elsewhere. “The situation has become even less predictable,” says Katzourakis.

Since Omicron appears to be milder than previous variants, surveillance efforts should aim to identify variants that cause severe disease in hospitalized patients, Gupta says. “I think that’s where we should focus our efforts, because if we keep focusing on new variants genomically, we might get a little tired, and then lose the ball when things happen.”

Many virologists acknowledge that the evolution of SARS-CoV-2 took them by surprise again and again. “It was really partly a failure of the imagination,” says Grubaugh. But whatever scenario researchers may envision, Bloom acknowledges that the virus will run its own course: “I think in the end we just have to wait and see what happens.”

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