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

But the tsunami that is the Omicron wave is tempting us all the same, in large part because of an inescapable fact: By the time it crashes, the immunological landscape in this country — and in much of the world — is going to be profoundly altered. Far more people will have some immunity to Covid-19 than was the case before the wave began. Many will have what is effectively hybrid immunity, from vaccination and infection.


As a result, some experts think we may 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 at the beginning of last summer.

Caveats abound, and most experts who spoke to STAT weren’t ready to predict that a reprieve, if it comes, will be an actual end to the pandemic — the point where SARS-2 pivots to becomes endemic. But they generally agreed that the accumulation of population immunity could slow things down, at least for a while.

“I think we will have a relative lull,” said Michael Osterholm, director of the University of Minnesota’s Center for Infectious Disease Research and Policy. He warned, though, that that lessening of Omicron’s grip is weeks away in most parts of the country. Even in places where case counts have started to decline, there are still a lot of infected people transmitting the virus. More will be infected before the wave ends.


“Few people will be naïve — completely naïve, no protection from either vaccination or natural infection — when the Omicron wave is over,” said Cecile Viboud, an infectious diseases epidemiologist and modeler at the National Institutes of Health’s Fogarty International Center.

That should lessen the spread of SARS-2 and take some of the heat out of the outbreak, said Scott Hensley, a vaccines researcher at the University of Pennsylvania’s Institute for Immunology.

Hensley is one of the people who believes Omicron is the final wave of the pandemic. If he’s correct, after this there will be so much immunity in many populations that transmission rates will drop and SARS-2 will transition into something more akin to the influenza-like illnesses that sicken people during the winter months, but are far less disruptive than the pandemic has been.

If transmission slows, hopefully so too will the virus’s accumulation of mutations.

“None of us think the virus is going to go away, but the virus will have less opportunity to change because there will be fewer hosts that it can replicate in,” said Hensley. “And in an immune population, due to immunity, disease severity will be less.”

It’s clear now that protection conferred by either vaccination or prior infection can wane over time. It’s also clear that SARS-2 viruses can mutate to at least partially evade the immune protections we acquire; that’s been a hallmark of Omicron. Both waning and immune evasion can lead to breakthrough infections among the vaccinated or repeat infections among those who have contracted the disease in the past.

But our accumulating immunity against SARS-2 — and changes in the intrinsic nature of the virus — have resulted in lower levels of severe disease in the Omicron wave. We don’t yet know how long that important type of immunity lasts — the type that keeps people from developing life-threatening illness when they contract the SARS-2 virus.

“We really at this point don’t know a lot about the levels of immunity that repeated infection might give one. How many times do you have to be infected to build up sufficient immunity to be sort of fairly reliably protected against severe disease?” asked Paul Bieniasz, head of the laboratory of retrovirology at Rockefeller University.

Likewise, we don’t know how much scope SARS-2 has to change to evade our immunity, or how broadly cross-protective the immunity tools we’ve acquired will be, if and when that happens, he said.

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

“The fact that most individuals that are vaccinated are protected against [severe disease from] Omicron leaves me hopeful that we’ll move into this sort of final chapter where the virus remains endemic, but we have to worry a lot less about severe disease,” Hensley said.

And people who contract Omicron will have even broader immune responses, said Deepta Bhattacharya, an immunologist at the University of Arizona. Though its constellation of mutations is unique, it is made up of individual changes that have been seen in other variants. “That really should buy us some more antigenic territory and hopefully some more time,” he said.

Bhattacharya believes there’s a possibility we’ll get a breather after Omicron. But he, like most of the people STAT spoke to for this story, raised a big caveat — the possibility that another out-of-the-blue variant, with new Houdini-like tricks for evading our amassed immunity, could come hurtling toward us.

Bhattacharya had thought the sustained Delta wave would be hard to top. Then came Omicron, evolving from another part of the evolutionary tree of SARS-2 viruses. He and others find this capacity of the virus unsettling — its seeming ability to reach back into its past to produce variants that aren’t offshoots of recent viruses but amplified echoes of ones that circulated earlier.

Omicron is “not a derivative of Delta and so that’s what makes it a little bit unpredictable as to what’s going to come next,” he said.

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

“I think people have this idea that Omicron’s the endgame. Anything that emerges [next] is going to emerge from Omicron, and then we’re into this low level, perhaps slightly seasonal endemic state,” Kucharski said. “But, given what we’ve seen previously, I think we have to be aware that there’s some uncertainty around that.”

John Moore, a virologist at Weill Cornell Medical College, said a post-Omicron decrease in transmission “is certainly a plausible scenario,” suggesting it might take until late February or early March for most of the country to get there. But equally possible, he suggested, is that another variant will emerge, with the transmissibility of Omicron but without its reticence to replicate in the deep lungs.

“This is where it’s all so freaking difficult. There are scenarios. You don’t know what the future’s going to hold. All these people who say ‘This is what’s going to happen.’ Well, this is what they think might happen, if they’re being honest,” he said.

Hensley, though, thinks any new variant will have a tough task after Omicron has swept through. “It’s hard to imagine … another variant being able to sustain itself in a population that just experienced this huge wave of Omicron.”

For his part, Bieniasz is feeling more optimistic than he was earlier in the Omicron wave, but he’s not looking for a respite. He wants something more sustained.

“I’m not so interested in breathers. These waves, I want to diminish the amplitude rather than the frequency,” he said.

In other words, a lot less Covid.

Correction: An earlier version of this article incorrectly described John Moore’s speciality. He is a virologist.

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