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After Omicron we could well take a break. We can only get it

By month 25 of the Covid-19 pandemic we should probably all have learned not to try to predict what the SARS-CoV-2 virus will do next. It has so consistently defied predictions.

But the tsunami, which is the Omicron wave, tempts us all, in large part because of an inevitable fact: When it crashes, the immunological landscape in this country - and in large parts of the world - will be profoundly changed. Far more people will have some immunity to Covid-19 than was the case before the wave began. Many want what is effective hybrid immunity, from vaccination and infection.

As a result, some experts believe we could get a bit of a break from the Covid roller coaster after Omicron. It could be a respite, if you will, after the punishing months of the Delta and Omicron waves with their millions of cases that began early last summer.

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There are plenty of caveats, and most experts who spoke to STAT were not ready to predict that a postponement, if it comes, would be a real end to the pandemic - the point where SARS-2 turns out to be endemic . But they generally agreed that the accumulation of population immunity could slow things down, at least for a while.

"I think we want a relative break," said Michael Osterholm, director of the University of Minnesota's Center for Infectious Disease Research and Policy. However, he warned that the reduction in Omicron's grip is weeks away in most parts of the country. Even in places where the number of cases has begun to decline, there are still many infected people transmitting the virus. More will be infected before the wave ends.

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"Few people will be naive - completely naive, no protection against either vaccination or natural infection - when the Omicron wave is over," said Cecile Viboud, an infectious disease epidemiologist and model builder at the National Institutes of Health's Fogarty International Center.

It should reduce the spread of SARS-2 and take some of the heat out of the outbreak, said Scott Hensley, a vaccine researcher at the University of Pennsylvania's Institute of Immunology.

Hensley is one of those people who believes that Omicron is the latest wave of the pandemic. If he is right, after this there will be so much immunity in many sections of the population that transmission rates will fall and SARS-2 will turn into something more like the flu-like diseases that make people sick in the winter months, but which is far less disruptive than the pandemic has been.

If the transmission slows down, hopefully so will the virus' accumulation of mutations.

"None of us think the virus will go away, but the virus will have fewer opportunities to change because there will be fewer hosts in which it can replicate," Hensley said. "And in an immune population, the severity of the disease will be less due to immunity."

It is clear now that protection given by either vaccination or previous infection may diminish over time. It is also clear that SARS-2 viruses can mutate to at least partially avoid the immune protection we achieve; it has been a hallmark of Omicron. Both declining and immunosuppression can lead to breakthrough infections among the vaccinated or recurrent infections among those who have previously contracted the disease.

But our accumulating immunity to SARS-2 - and changes in the inherent nature of the virus - have resulted in lower levels of severe disease in the Omicron wave. We do not yet know how long the important type of immunity lasts - the type that prevents people from developing life-threatening disease when they get the SARS-2 virus.

"We really do not know much at the moment about the level of immunity that repeated infection can give one. How many times must one be infected to build up sufficient immunity to be reasonably reliably protected from serious illness?" asked Paul Bieniasz, head of the laboratory for retrovirology at Rockefeller University.

Likewise, we do not know how much extent SARS-2 needs to be changed to avoid our immunity, or how broadly cross-protective the immunity tools we have acquired will be if and when that happens, he said.

But Hensley sees a promise in the fact that current Covid vaccines, which target a very different strain of the virus, can still protect against serious disease in the Omicron wave.

“The fact that most individuals who are vaccinated are protected against [severe disease from] "Omicron leaves me with hope that we will move into this kind of final chapter where the virus remains endemic, but we need to worry much less about serious illness," Hensley said.

And people who get Omicron will have even broader immune responses, said Deepta Bhattacharya, an immunologist at the University of Arizona. Although its constellation of mutations is unique, it consists of individual changes seen in other variants. "It should really give us some more antigenic territory and hopefully some more time," he said.

Bhattacharya believes that there is a possibility that we will get a respite after Omicron. But he, like most of the people STAT spoke to for this story, raised a big warning - the possibility that another out of the blue variant, with new Houdini-like tricks to circumvent our accumulated immunity, could come storming against us .

Bhattacharya had thought the sustained Delta wave would be hard to top. Then came Omicron, which evolved from another part of the evolutionary tree of SARS-2 viruses. He and others find this capacity of the virus disturbing - its apparent ability to go back to its past to produce variants that are not offspring of newer viruses, but amplified echoes of those that circulated in the past.

Omicron is "not a derivative of Delta, and so that's what makes it a little unpredictable in terms of what's going to come next," he said.

Adam Kucharski, associate professor of epidemiology of infectious diseases at the London School of Hygiene and Tropical Medicine, agreed. In a recent Twitter thread, Kucharski warned that the unusual way in which SARS-2 variants have evolved makes the future path of the virus difficult to predict. The most beneficial feature of Omicron - its penchant for replicating in the upper respiratory tract, not deep in the lungs, where it could trigger pneumonia - may not be a facet of which version of SARS-2 comes next, he warned.

"I think people have the idea that Omicron is the endgame. Everything that comes up [next] is going to emerge from Omicron, and then we are in this low level, maybe a little seasonal endemic state, ”Kucharski said. "But given what we've seen before, I think we need to be aware that there's some uncertainty around that."

John Moore, a virologist at Weill Cornell Medical College, said a drop in transmission after Omicron "is certainly a plausible scenario", suggesting it may take until late February or early March for it most of the country to get there. But just as possible, he suggested, is that another variant will emerge, with the transferability of Omicron, but without its reluctance to replicate in the deep lungs.

"This is where it's all so wildly difficult. There are scenarios. You do not know what the future will bring. All these people who say 'This is what's going to happen.' Well, that's what they're thinking power happen if they are honest, ”he said.

However, Hensley believes that any new variant will have a difficult task after Omicron has been swept through. "It's hard to imagine… another variant that is able to sustain itself in a population that has just experienced this huge wave of Omicron."

For his part, Bieniasz feels more optimistic than he was earlier in the Omicron wave, but he's not looking for a respite. He wants something more sustainable.

"I'm not that interested in breathing. These waves, I want to decrease the amplitude rather than the frequency, "he said.

In other words, much less Covid.

Correction: An earlier version of this article incorrectly described John Moore's thesis. He's a virologist.

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