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Where did the coronavirus omicron variant come from? Scientists suggest it evolved in one person.

Charles Darwin could have learned a thing or two about evolution from the SARS-CoV-2 virus. As it has passed back and forth across the world over the past two years, the pandemic-causing virus has changed, sometimes bit by bit; in the case of the omicron variant, seemingly in many ways at one time.

Scientists say these changes can be explained by how the coronavirus works, and how infecting people can drive mutations.Unlike some viruses, the SARS-CoV-2 virus that causes COVID-19 has a self-correcting mechanism – like spell-check – fixing some of the random mistakes it makes as it copies itself. The coronavirus typically only changes about 2 of the 30,000 letters in its genome a month as it transmits from person to person. But when someone with a weakened immune system tries to control the virus, it can shape-shift to avoid its own destruction.

Studies have shown that people in treatment for cancer, immunosuppressed after an organ transplant or weakened by HIV can remain infected with COVID-19 for months, while the coronavirus accumulates changes that make it harder to wipe out. No “patient zero” has been found for omicron or any other variant, but scientists think they likely evolved within a single immunocompromised person.

“It’s reasonable speculation, but we don’t know for sure,” said Jesse Bloom, who studies viral evolution at the Fred Hutchinson Cancer Research Center in Seattle. An early glimpse of omicron’s threat:

High transmission likely, but vaccines provide hopeOmicron has 50 spelling changes from the original version of the virus, including 30 on the spike proteins that sit on the surface of the virus and are the target of vaccines and some treatments.

Those changes didn’t evolve one at a time as the virus passed from one person to another, surveillance data suggests, but seem to have arrived together – lending support to the idea that they co-evolved within a single person.

Experts say it’s too soon to know whether all those changes will make the variant less subject to protection from vaccines and previous infections, or whether it will be able to evade monoclonal antibody treatments. Winning the arms raceFor one variant to take over, it has to beat out others, either by transmitting more effectively or by being able to make more copies of itself once it reaches a new host.

“If it transmits well but doesn’t replicate well in its new host, it’s not as likely to win out in the end, because it’s got a dead-end path,” said Dr. Bruce Walker, an immunology professor at Harvard Medical School and the Massachusetts Institute of Technology.

Mutations that offer a survival advantage “can get into more people and create more viruses to infect more of the species,” he said. In a normal person, whose immune system clears the virus in about a week, there’s not much time for mutations to accumulate, said Walker, also director of the Ragon Institute of MGH, MIT, and Harvard, an interdisciplinary immune research center.

But in an immunocompromised person, the virus might linger for months, studies show. Testing on one 45-year-old American with an immune condition that caused blood clots, showed his body was infected with COVID-19 for more than five months. A 58-year-old German man who’d just had a kidney transplant was hospitalized for six months in 2020 with a lingering case. And 60-year-old American with lymphoma, a type of blood cancer, struggled with COVID-19 for more than five months before eventually seeking hospice care.This gives the virus plenty of time to accumulate random changes that work to its advantage. “Even within a person, you can select for increased transmissibility from one cell to another and you can select for better replication,” Walker said.

Understanding omicron: How the latest coronavirus variant, now in the US, is mutating and spreadingSurprisingly, a person who is infected for that long might not even know it, said Karin Moelling, a virologist affiliated with the University of Zurich and the Max Planck Institute for Molecular Genetics in Berlin.

In a study she published in April, she traced the case of a woman who tested positive for the novel coronavirus for 105 days – but had no symptoms. Moelling thinks people who are immunocompromised don’t mount a response to the virus, so they have no symptoms – even though they might be able to pass a highly mutated form of the virus to someone else. Everyone who has an immunocompromising condition should be routinely tested for the virus, to make sure they’re not breeding variants, she said. Vaccines may not be as effective for people who can’t mount a full immune response, and variants like omicron may make monoclonal antibodies less protective in this population, she said.

So far, though, many immunocompromised people around the world haven’t even been vaccinated. In a November study of nearly 7,000 people with HIV, researchers from Massachusetts General Hospital found that about 72% of those in the U.S. had been vaccinated, compared to just 18% in South Africa and none in Haiti.

Why evolution matters  Omicron represents the virus evolving to evade the human immune system – first probably in a single individual and now in more people, said Dr. Jonathan Abraham, a Harvard Medical School immunologist who has been studying the evolution of the SARS-CoV-2 virus.

Multiple previous exposures to parts of the virus provide the best protection against COVID-19, Abraham said. Full vaccination plus boosting when immunity wanes is probably best at safely teaching the immune system to recognize and remember the virus, he said.

Even if someone with three exposures catches COVID-19, they’re unlikely to become seriously ill, he and others said.”It’s not going to totally disregard prior exposure,” Dr. Roger Shapiro, an associate professor of Immunology and infectious diseases at the Harvard T.H. Chan School of Public Health, said last week in a call with reporters. “Other aspects of the immune system should keep us out of the hospital, even though it looks like it’s blowing right through that prior exposure.”But the omicron variant could pose serious problems for people with fewer than three solid exposures, Abraham said, or for those whose immune systems are too weak, because of illness or medication, to mount a full response.

Endless mutations? Is the new COVID-19 normal a new, worrisome variant every few months?Abraham led a study published Thursday looking at different combinations of mutations that cropped up in immunocompromised people or had been been seen in rare instances in the general population. Based on the location of those mutations compared to mutations in omicron, he worries the new variant will be able to evade monoclonal antibodies – which have been used to prevent serious disease in people at highest risk.

He’s also concerned that people who only had one shot, who received ineffective vaccines (from countries outside the U.S. or Europe) or who recovered from COVID-19 but haven’t been vaccinated, might have incomplete immunity. Exposure to incomplete immunity could allow the virus to learn how to escape protection”Are vaccines driving the virus to become more dangerous? No,” Abraham said. But there are cases where “suboptimal” protection could drive the SARS-CoV-2 virus to evolve away from preventions, treatments and natural immunity from infection.In this context, “the virus will learn how to do a better job of escaping human immunity. It will probably learn how to over time defeat that first generation of vaccines,” he said.

Although not much is known about omicron yet, it’s clear that it can infect people who have been vaccinated or previously infected. This suggests the virus is adapting to this partial immunity – making it even more important for people to get protected by vaccines, he said.”You want to avoid bad immunity and get the best immunity possible,” he said. “We can’t think we’re done with the virus, because the virus is not done with us yet.”

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