What Happens After Omicron? Four Key Questions About Where The Pandemic Goes Next.

“I think in many ways, we are just as flabbergasted as the rest of society about how Omicron has seemingly come from nowhere,” one scientist said.

The Omicron variant’s worldwide surge has upended early hopes for returns to normalcy and points to a more uncertain future for the pandemic, some experts say. The advent of the variant has shaken many scientists who were once confident that they had a handle on SARS-CoV-2.

“I think in many ways, we are just as flabbergasted as the rest of society about how Omicron has seemingly come from nowhere and seemingly spread so quickly,” said infectious disease expert Jacob Lemieux of Massachusetts General Hospital.

First identified in November, just two months ago, Omicron has led to global case reports of around 3 million new cases a day worldwide, nearly a fifth of them in the US. In the last week, cities such as New York, Boston, and Washington, DC have reported signs that COVID cases have started to decline, echoing earlier drops seen overseas in the United Kingdom and in South Africa.

The CDC’s assembly of forecasts for COVID cases project the US peak coming nationwide in the next two weeks, heading up to 800,000 new cases a day before a sharp decline. Those same forecasts predict COVID-19 deaths approaching 3,000 a day in the US in February — nearly doubling the current, already awful rates — as the variant cuts its deadly swath through the country.

Observed and forecast COVID cases for US / CDC

“We are going to have a tremendous number of deaths among the unvaccinated,” said immunologist John Wherry of the University of Pennsylvania School of Medicine. “And we’re going to have — even if we manage to eke our way through this — the scar tissue in the health system, which is going to last for a long time and is not going to be something that recovers when infection rates go down.”

Shaken scientists, meanwhile, are reassessing their understanding of the SARS-CoV-2 virus in the aftermath.

In three months, the Omicron variant has dramatically redefined how bad a COVID surge can be, even when vaccines are readily available. The new reality raises hard questions about what will happen after Omicron recedes.

Here’s everything we know about what might happen next.

Will there be a lull?

In South Africa and the United Kingdom, a steep decline in Omicron cases has raised hopes that the winter surge will be followed by a spring lull. With increased population immunity from vaccination and the tornado of infections that has swept the US, as well as the rollout of hundreds of millions of antiviral pills promised by the Biden administration for this year, it’s possible the next chapter of the pandemic will be that of a virus in retreat, one defanged but not defeated.

Our post omicron world: 1. Omicron goes down 2. It fails to produce herd immunity, durable protection 3. We’ll have 6 mo to vaccinate the world & prevent a new variant from emerging this summer 4. It may not resemble omicron 5. Vaccinating world in next 6 months = our best path

Twitter: @PeterHotez

Scott Hensley, a vaccine expert at the University of Pennsylvania, told Stat that he expects those factors will make Omicron the last wave of the pandemic. Coronavirus infections continue in this case, but they rarely lead to deaths or hospitalization. We return to a world without masks, shuttered offices, or canceled public events.

But many other scientists are less optimistic. They argue that there are no guarantees that US case numbers will fall to where they were before the Omicron surge began, for example.

Lots of soothsayers predicting Omicron peaking soon in the US. That would be most welcome, yet begs the question, what comes next? Shangri-La? S. Africa (graph ⬇️) took a month to peak & now, 3 weeks post peak, incidence is still is 25X above the pre-Omicron baseline. 1/

Twitter: @DocJeffD

“I don’t know, unfortunately, that we can rely on what’s happened in other countries and expect that’s going to happen here, because it hasn’t in the past,” said immunologist Deepta Bhattacharya of the University of Arizona. The US experience with past surges has been a sharp peak and then a gradual decline that instead never really settles down to particularly low case numbers.

The aftermath of Omicron may be a patchwork of different experiences, both around the globe and across the country. “We’re starting to get a sense of what happens now after Omicron,” Lemieux of Massachusetts General Hospital said, speaking Tuesday at a briefing for reporters. “And we’re seeing not a single consistent behavior.”

In some places after an Omicron surge, there is a resurgence of the Delta variant. In others, Omicron has been replaced by a sister “stealth” lineage of the Omicron variant called “B.A.2,” seen rising in Denmark and India. That means the post-Omicron pandemic may look different everywhere.

“I don’t think we’re out of the woods yet. I do think things will get better,” Lemieux said. “But we’re going to have to keep a really close eye on the evolution of this virus because that has continued to be a major factor in the pandemic to date, and I don’t expect that to change.”

Is Omicron really that different from the other variants?

It’s possible that we may eventually see Omicron as just another variant that caused one of many surges in a long-running pandemic. So far, the World Health Organization has tallied five “variants of concern,” with Omicron only the latest. Each one has told scientists a little more about the SARS-CoV-2 virus.

But among scientists, there is wide agreement that Omicron has been a landmark variant. They say its arrival is a turning point in the pandemic, though no one knows what it’s pointed us toward.

“Oh, I think it’s a very significant, very, very significant event,” Wherry said. He said many members of the scientific community were surprised that a variant like this could emerge.

Clearly observable factors, such as Omicron’s large number of mutations, higher transmission rate, and ease in piercing through vaccine immunity, are all forcing a recalibration in thinking about the virus.

“Omicron has been both surprising and concerning from a scientific perspective,” said immunologist Shane Crotty of the La Jolla Institute for Immunology. It was surprising that the variant picked up so many mutations, more than 50 overall, and transmitted itself so well. It shook preconceptions of how much room the virus had to evolve. “That’s concerning both for immunity and efficacy of vaccines, but also the future of the pandemic.”

“It shows that this virus is more flexible than most of us had expected,” he said. “That’s worrisome.”

Omicron sports 32 mutations on the spike protein that the virus uses to latch onto cells. That’s about three times more than in past variants. The fact that the virus could change so much and remain infectious forces scientists to consider a wider field of possibilities for future mutations of the virus.

“The bet was that the virus couldn't have very many mutations without the spike protein just becoming a mess,” Crotty said, “but somehow it managed to do that and still be pretty functional, which means looking into the future, the virus might be able to do a lot of that repeatedly.”

Do Omicron’s milder effects mean future variants will be less severe?

Statistically, Omicron does appear less likely to lead to death than the previously dominant Delta variant. A recent Case Western Reserve preliminary study of 84.5 million patient records, still not peer-reviewed, found the risk of hospitalization or death from Omicron was less than half of Delta, for example.

“Anecdotally, this surge feels very different on the wards,” said pediatric infectious disease expert Andrea Ciaranello of Massachusetts General Hospital at the Tuesday briefing. Doctors are seeing many more cases, but far fewer pregnant women are being sent to an ICU or need to be urgently intubated or induced at her hospital. “I think we may be benefiting from our very high vaccination rate here.”

However, the risks are still real, Ciaranello added. Scientists are still trying to untangle whether Omicron truly causes milder disease, or whether it just seems milder because more vaccinated people are getting sick and they are largely protected from the worst outcomes.

“Being mild, that’s the biggest misconception right now,” Crotty said. “Definitely in vaccinated people, Omicron has almost universally been mild, and that’s fantastic.” But all that means is that the Omicron variant is still about as deadly as the original, wild-type virus, though it is less deadly than Delta, he said. “The original strain obviously caused huge problems.”

Moreover, he called the notion that viruses inevitably evolve to become less deadly to their hosts “a fairy tale” that might make it easier to sleep at night, but offers no insight into the future of the coronavirus.

Rotaviruses, which kill hundreds of thousands of children worldwide from diarrheal disease every year, have evolved to become more virulent, for example. A Viking Age sample of a smallpox virus reported in 2020 suggests that the virus, which famously killed 30% of the people it infected in the 20th century, was once a milder disease.

While in the big picture killing your host might be a bad idea for any virus that wants to spread, the double-barreled nature of a COVID case complicates such thinking about SARS-CoV-2, Bhattacharya said. The virus first infects the nose, throat, and mouth, transmitting new infections to new hosts from there, and only invades the lungs days later, a stage of the disease that doesn’t matter to the spread of the virus. Thus lung infection is not all that important to its evolution. But infecting the lungs is what kills people. “If the truth is that it is intrinsically more mild, that’s happenstance,” Bhattacharya said. This means whether the next widespread variant is more or less dangerous than Omicron is just a matter of chance.

The threat of a more deadly and more transmissible variant arising is more than just theoretical. Some of the mutations (related to the fusion of an invading virus to a cell) that made Delta more dangerous aren’t carried by Omicron yet, but they have been spotted on a few versions of the variant in a few places, Crotty said.

“It’s not some distant hypothetical thing,” he added. “It is a concern right now. People are watching around the globe for this intently.”

On the plus side, the ability of coronavirus vaccines to stand up against severe disease is encouraging after Omicron, he said, and a testimony to the immune system. “It’s like you showed the immune system one kind of coffee mug, a round thing with a handle, and from that it was able to recognize every kind of mug that you can imagine. It’s remarkable.”

Will humanity have heightened immunity after Omicron?

Probably. The huge number of infections caused by Omicron will likely leave behind some kind of strengthened immunity against the coronavirus in its wake. Around 60% of the world’s population has now received at least one vaccination as well, which changes the landscape faced by the virus.

“We do have a degree of population immunity now that means, if you have immunity, the chances of you ending up in the hospital or having real life-threatening consequences are dramatically lower,” said Wherry, the Penn immunologist. “And that’s a game changer.”

Just how much immunity an Omicron infection adds to anyone’s armory is uncertain, however, and might vary from person to person, depending on the impression an infection left on their immune system. “I’m sure that there’ll be a new variant at some point. The question is whether Omicron might buy us a little more time before the next serious variant of concern,” Bhattacharya said.

On the other hand, just as Omicron’s mutations added up to a big jump away from past variants, the next serious variant might be a big jump in a different direction. That seems more possible now because Omicron showed there is extra maneuvering room for the virus to mutate significantly and still infect.

The coronavirus infects everything from lions to deer, and billions of people remain unvaccinated, providing plenty of hosts for new viral evolution.

“I and other people who are thinking about this are a little reluctant to say, ‘Yeah, [Omicron immunity] will buy us more time,’ because Omicron kind of came out of left field,” Bhattacharya said.

This means the really big remaining need after Omicron is to vaccinate the globe, Ciaranello said. “We saw the last couple variants emerge from largely unvaccinated populations.” She said we may have gotten lucky with Omicron, which is sending fewer people to the ICU in her hospital right now. “We may not get so lucky next time. And we really need to continue to push the vaccine makers and the government to get vaccines to the globe.”

In the long run, the combination of global vaccination and whatever immunity comes from infections should at some point result in a final wave of the pandemic. For other coronaviruses, ones that cause common colds, new variants of concern typically arise every three to five years. Hopefully at some point, SARS-CoV-2 evolves into that groove, causing colds but not disrupting life.

“Whether that’s 18 months from now, or 18 years from now, I’m not sure,” Wherry said. “But that’s likely where we’re gonna end up.”

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