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Three unknowns will define this pandemic winter

Winter has a way of bringing out the worst of the coronavirus. Last year the season saw a record wave that almost 250,000 Americans dead and hospitals across the country overwhelmed. This year we are much better prepared, with effective vaccines – and soon powerful antivirals – that fight the coronavirus, but the number of cases seems to be rising again, raising fears of another big wave.

How bad will it get? We are no longer in the most dangerous phase of the pandemic, but we have not reached the end either. Thus, the trajectory of COVID-19 in the coming months will depend on three key unknowns: how our immunity holds up, how the virus changes, and how we behave. These unknowns may also turn out differently, state to state, city to city, but together they will determine what happens this winter.

How much immunity do we even have?

Here are the basic numbers: The US is fully vaccinated 59 percent of the country and registered enough cases to represent 14 percent of the population. (Although, given the limited testing, these case numbers almost certainly underestimate real infections.) What we don’t know is how to put these two numbers together, says Elizabeth Halloran, an epidemiologist at the Fred Hutchinson Cancer Research Center. What percentage of Americans have immunity to the coronavirus – through vaccines or infection or both?

This is the key number that will determine the strength of our immunity wall this winter, but it’s impossible to determine with the data we have. This uncertainty matters because even a small percentage difference in overall immunity translates into a large number of susceptible people. For example, an additional 5 percent of Americans without immunity are 16.5 million people, and an additional 16.5 million infections could mean hundreds of thousands more hospitalizations. Because unvaccinated people tend to cluster geographically and because many hospital intensive care units are running close to capacity even in non-pandemic times, it doesn’t take many sick patients to overwhelm a local health care system.

What’s happening in Europe, says Ali Ellebedy, an immunologist at Washington University in St. Louis, is also a “red sign.” Several countries in Western Europe, which have been vaccinated more strongly than the US, are already seeing peaks towards the winter. The number of cases in Germany, which has vaccinated nearly 70 percent of the population, has risen sharply, has overwhelmed hospitals and the incentive has been renewed restrictions for unvaccinated. The US has slightly more immunity to previous infections than Germany because it has had bigger COVID waves, but it still has a lot of susceptible people.

The strength of immunity also varies from person to person. In particular, immunity to a previous infection can be quite variable. Vaccine-induced immunity tends to be more consistent, but older people and immunocompromised people react weaker. And everyone’s immunity to infections clearly declines over time, which means that breakthrough infections are becoming more common. Boosters, which will soon be available to all adults, could counteract the decline this winter, although we don’t yet know how durable that protection will be in the long run. If the sum of all this immunity is on the high side, this winter could be relatively mild; if not, we can expect another tax wave.

Will new variants emerge?

At the start of the pandemic, scientists thought this coronavirus mutates quite slowly. Then, in late 2020, a more portable Alpha variant came along. And then a even more transferable Delta variant emerged. In a year, the virus has more than doubled its contagiousness. The evolution of this coronavirus may be slowing down now, but that doesn’t mean it has stopped: we can expect the coronavirus to keep changing.

Alpha and Delta were evolutionary winners because they are so contagious, and the virus could potentially find ways to increase its transmissibility even more. But as more people become vaccinated or infected, our collective immunity increasingly gives an edge over variants that can escape the immune system instead. Delta already has some of this capability. In the future, says Sarah Cobey, an evolutionary biologist at the University of Chicago, “I think most fitness improvements will come from immune escape.”

The beta and gamma variants also compromised immune protection, but they could not compete with the current Delta variant. There may be other variants that can. Whether this will all happen in time to make a difference this winter is impossible to know, but it will eventually. This is simply how evolution works. Other coronaviruses that cause the common cold change every year too– just like the flu. The viruses always cause reinfections, but each reinfection also refreshes the immune system’s memory.

A new variant could change the pandemic trajectory again this winter, but the pandemic clock is unlikely to be set back to March 2020. We may end up with a variant that causes more breakthrough infections or reinfections, but our immune system isn’t going to be completely fooled.

How will people spread the virus?

The coronavirus isn’t jumping on planes, driving across state lines, or going to holiday parties. We do. COVID-19 spreads when we spread it, and predicting what people will do has been one of the biggest challenges in modeling the pandemic. “We’re constantly surprised when things are messier and weirder,” said Jon Zelner, an epidemiologist at the University of Michigan.

For example, the Delta wave in the Deep South in the summer ebbed away in late summer and early fall, although many COVID restrictions did not recur. You might have expected at the time that the number of cases would increase as schools full of unmasked and unvaccinated children reopened. So what happened? One possible explanation is that people became more cautious about masks and social distancing when they saw cases emerging around them. More people in the South are vaccinated, although the rates still lagging behind those in the highly vaccinated northeast. Are spikes “self-limiting because people adjust their behavior in response to recent spikes?” says Cobey. “That’s just a very open question.” The weather can also drive behavior; as temperatures cooled in the south, people may have spent more time outdoors.

Another possible factor in ending the summer wave is that the virus may have just infected everyone who could find it at the time, but that’s not the same as saying it infected everyone in those states. The coronavirus does not spread evenly across a region, like ink through water. Instead, it must travel along networks of connection between people. COVID-19 can go through an entire household or workplace, but it can’t jump to the next one unless people get in the way. By sheer coincidence, in a given wave, the coronavirus can find some pockets of susceptible people, but not others. “There’s a kind of randomness in it,” Zelner says. This winter, we should expect a local flare-up whenever the virus finds a barrel of susceptibility. But it is difficult to predict exactly when and where that will happen. The country’s current COVID hotspots are Michigan, Minnesota and New Mexico, three states with no apparent connection between them.

By winter’s end, the US will emerge with more immunity than it does now — either from infection or, much rather, by vaccinating more people. “For me, this winter is the last stand,” says Zelner. However these three unknowns turn out this winter, COVID will eventually begin to fade as a disruptive force in our lives as it becomes endemic. We’re not quite there yet, but our second pandemic winter will bring us one step closer.