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The emergence of a new Covid-19 variant with a startlingly large constellation of mutations has countries around the world sounding alarms. While the concerns are understandable, experts in immunology say people need to remember a critical fact: Two years and 8 billion vaccine doses into the pandemic, many immune systems are no longer blank slates when it comes to SARS-CoV-2.

The new SARS-2 variant, known as Omicron, may more easily sidestep some of the immunity of some vaccinated and previously infected people. But there’s good reason to think people who already have some immune protections may avoid the worst of what Covid infections can do to immunologically naïve people.

“Dealing with naïve people is never the same as if you have some memory. It’s never like [being back at] square one,” Ali Ellebedy, an associate professor of pathology and immunology at Washington University School of Medicine in St. Louis, told STAT. “The virus is going to not find it as easy compared to the situation in January 2020 or December 2019. It’s just completely different now.”

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He cautioned, however, that that is more true in some parts of the world — in other words, affluent countries — than it is in others. “I think the folks who will suffer most are the completely unimmunized or immunized with very weak vaccines, like most of the developing world.”

The new variant may well erode some of the protection induced by vaccines, or by prior Covid infection. If Omicron takes off, there may be larger numbers of breakthrough infections among the vaccinated and more reinfections among the previously infected. But a smaller portion of those infections may develop into cases of serious or severe disease.

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“One would think that even if now at the get-go you don’t have a neutralizing antibody response, there might still be a safety net there. And that safety net may be relatively stable when we talk about infection,” said Florian Krammer, a professor of vaccinology at the Icahn School of Medicine at Mount Sinai Hospital in New York.

There are real worries that some of the mutations in the spike protein of Omicron variant viruses will undermine the efficacy of the neutralizing antibodies generated after vaccination. While the correlates of protection for SARS-2 — the types and amounts of immune system weapons needed to be protected against it — aren’t yet fully defined, neutralizing antibodies clearly play an important role in protection. And their waning seems to presage a rise in the risk of breakthrough infection.

Kristian Andersen, an immunologist at the Scripps Research Institute, is among those worried about how big a dent Omicron may put into SARS-2 acquired immunity.

“I think we’ll see very significant degradation of immune protection, whether that be by infection-induced immunity and possibly also via vaccine-derived immunity, especially as it comes to the ability to protect against infection and transmission,” Andersen said.

He acknowledged other immune system weapons — T-cells and other types of antibodies — will recognize and respond to the virus. “But the concern is that we don’t really know the role of T cells. For example, exactly how much are they or are they not protecting against disease, infection, transmission, all these different things? Because it really does seem like our level of neutralizing antibodies correlates really well with the ability to protect,” he said.

Anna Durbin, director of the Center for Immunization Research at Johns Hopkins Bloomberg School of Public Health, said T cells — which have been trained by vaccine or infection to look for and attack a particular pathogen, in this case SARS-2 — may not be enough to prevent infection with the Omicron variant, but should help shut down the disease it triggers, if infection occurs.

“You will have some protection if you were vaccinated,” Durbin said. “Our immune systems have seen parts of that spike protein before.”

Barney Graham, former deputy director of the Vaccine Research Center at the National Institutes of Health, said he too would expect people with some pre-existing immunity to SARS-2 will have T cells and antibodies that cross-react with the new variant; they will kick into gear if the person contracts the virus.

“It will help people make a more rapid immune response [though] maybe not as quickly as a fully matched vaccinated person,” said Graham, who retired at the end of August. “We’re not a blank slate anymore. We have a lot of complex, nuanced immunity that may not be perfectly matched, but it is going to overall give us an advantage that we didn’t have two years ago.”

It will take time to see what the impact of Omicron’s mutations are, said John Moore, an immunologist at Weill Cornell University. And it will also take time to see whether the new variant will spread broadly. Some variants of concern have not, including the Beta variant — first reported by South Africa last December — which had mutations that were shown to erode the effectiveness of some of the Covid vaccines. That variant, though, never took off.

Will Omicron be another Beta, or a super Delta? It will take a while for the answer to come into focus, Moore said. But either way, many people do have an immunological foundation for SARS-2 at this point.

“The likelihood is that any compromise won’t be complete. I mean, there can be some compromise to the immune … response, but it won’t be complete,” he said.

Graham noted there are other ways in which the world is in better position to fight Omicron than it would have been two years ago.

“The thing we have now is we know how to make [Covid] vaccines, we know how to make drugs, we know how to make monoclonal antibodies,” he said. “And if we have to, we can make new vaccines and antibodies for this new virus.”

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