While Omicron rages, scientists do not know what will happen next

(ORDO NEWS) — In the short history of the COVID-19 pandemic, 2021 has been a year of new options. Alpha, Beta, Gamma and Delta spent several months on the Sun.

But it was the year of Omicron that swept the globe at the end of 2021 and continues to dominate, with more prosaic-named sub-variants like BA.1, BA.2 and BA.2.12.1 appearing quickly.

Two closely related subvariants called BA.4 and BA.5 are currently causing infections worldwide, but new candidates, including one called BA.2.75, are knocking on the door.

Omicron’s continued dominance has evolutionary biologists wondering what’s next. Some believe that this is a sign that the initial frenzied development of SARS-CoV-2 is over, and, like other coronaviruses that have lived with humanity for much longer, it is moving into a stage of gradual evolution.

“I think it’s safe to assume that BA.2 or BA.5 will give rise to additional offspring with more mutations, and that one or more of these subvariants will spread and become next,” says Jesse Bloom, an evolutionary biologist at the Fred Hutchinson Cancer Research Center. .

But others believe that a new variant, different enough from Omicron and all other variants to merit the next Greek letter designation Pi, is already developing, possibly in a chronically infected patient.

And even if Omicron is not replaced, its dominance is not a reason for complacency, says Maria Van Kerkhove, technical lead for the COVID-19 project at the World Health Organization. “It’s bad enough as it is,” she says. “If we can’t get people to act [without] a new Greek name, that’s already a problem.”

Van Kerkhove points out that even with Omicron in place, the world could face relentless waves of disease as immunity wanes and new sub-variants emerge.

She is also concerned that surveillance efforts, which allowed researchers to detect Omicron and other new variants early, are being scaled back or phased out. “These systems are being dismantled, their funding is cut off, people are being fired,” she says.

The options that will rule in 2021 did not spring from one another. Instead, they evolved in parallel from the SARS-CoV-2 viruses circulating at the beginning of the pandemic.

On viral lineages that researchers draw to visualize the evolutionary relationships of SARS-CoV-2 viruses, these variants appeared at the tips of long, bare branches. This picture seems to reflect that the virus hides in one person for a long time and evolves before appearing and spreading again, having changed significantly.

More and more research confirms that it occurs in immunocompromised people who cannot clear the body of the virus and have long-term infections. For example, on July 2, Yale University genomic epidemiologist Nathan Grubo and his team published a preprint on the medRxiv website about one such patient that they accidentally discovered.

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, despite the fact that this lineage should have disappeared from society long ago.

As it turned out, all samples were obtained from the same person – a patient with a weakened immune system at the age of 60, who was undergoing treatment for B-cell lymphoma. He was infected with B.1.517 in November 2020 and has remained positive so far.

By following his infection and watching how the virus changed over time, the team found that it evolved twice as fast as SARS-CoV-2 normally does. (According to Grubo, some of the viruses circulating in the patient’s body today could be qualified as new variants if they were found in society.)

This supports the hypothesis that chronic infections may contribute to the “unpredictable emergence” of new variants, the researchers write in their preprint.

Other viruses that chronically infect patients also change faster within one host than when spreading from one person to another, says Aris Katsourakis, an evolutionary biologist at the University of Oxford.

This is partly a numbers game: Millions of viruses replicate in the human body, but only a few of them are transmitted by transmission. Thus, many potential evolutionary opportunities are lost in the chain of infections, while chronic infection provides endless opportunities for evolution.

But since the introduction of the Omicron in November 2021, no new variant has popped up out of nowhere. Instead, the omicron accumulated small changes that allowed it to better avoid immune responses and – along with a weakened immune system – led to more waves.

“I think it’s probably harder and harder for new species to emerge and take over because all the different Omicron lineages are tough competition,” says Grubo, given how much they’re already transmissible and immunocompromised.

If so, then the US decision to update COVID-19 vaccines with an Omicron component is the right move, Bloom says; even if Omicron continues to change, a vaccine based on it is likely to provide more protection than a vaccine based on earlier options.

But there is still the possibility of an entirely new variant unrelated to the omicron. Or one of the previous variants, like Alpha or Delta, could come back, causing a chronic infection and going through a period of accelerated evolution, says Tom Peacock, a virologist at Imperial College London: “These are what we call second-generation variants.”

Given these opportunities, “the study of chronic infections is now more important than ever,” says Ravindra Gupta, a microbiologist at the University of Cambridge. “They can tell us which way the virus will mutate in the population.”

The BA.2.75 virus, which was discovered recently, is already causing concern among some scientists. Nicknamed Centaurus, it evolved from Omicron, but seems to have quickly accumulated a number of important changes in its genome, more like a completely new variant than a new sub-variant of Omicron. “It looks exactly like Alpha or Gamma or Beta,” Peacock says.

BA.2.75 appears to be distributed in India, where it was first identified, and has been found in many other countries. Whether it actually outperforms the other sub-options remains to be seen, Van Kerkhove says: “Data is very limited right now.” “I definitely think it’s something to keep a close eye on,” says Emma Hodcroft, a virologist at the University of Bern.

However, keeping track of everything is becoming increasingly difficult, because the scope of surveillance is reduced. Switzerland, for example, now takes about 500 samples per week, down from the 2,000 samples at its peak, says Hodcroft; The United States, from more than 60,000 samples per week, dropped to about 10,000 in January.

“Some governments are looking to reduce the funds they allocate for sequencing,” says Hodcroft. Defending the costs is “not an easy task,” she says, “especially if it feels like the countries around you will continue sequencing even if you stop.”

Even if a variant appears in a country with good surveillance, predicting how much of a threat it poses may be harder than in the past, as differences in past COVID-19 waves, vaccines, and immunization schedules have created a global immunity chessboard.

This means that a new variant may perform well in one place, but hit a wall of immunity in another. “The situation has become even less predictable,” says Katzourakis.

Given that Omicron appears to be milder than previous options, surveillance efforts should focus on identifying options that cause severe disease in hospitalized patients, Gupta says.

“I think that’s where we should be focusing our efforts, because if we keep focusing on new variants of the genome, we can get a little tired, and then kind of miss the moment when something happens.”

Many virologists admit that the evolution of SARS-CoV-2 has taken them by surprise time and time again. “Part of it was a failure of the imagination,” says Grubo. But whatever scenario the researchers envision, Bloom acknowledges that the virus will take its course: “I think ultimately we’ll just have to wait and see what happens.”


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