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Winter has a way of bringing out the worst of the coronavirus. Last year, the season saw a record surge that left nearly 250,000 Americans dead and hospitals overwhelmed around the country. This year, we are much better prepared, with effective vaccines—and, soon, powerful antivirals—that defang the coronavirus, but cases seem to be on the rise again, prompting fears of another big surge.

How bad will it get? We are no longer in the most dangerous phase of the pandemic, but we also have not reached the end. So COVID-19’s trajectory over the next few months will depend on three key unknowns: how our immunity holds up, how the virus changes, and how we behave. These unknowns may also play out differently state to state, town to town, but together they will determine what ends up happening this winter.

How Much Immunity Do We Even Have?

Here are the basic numbers: The U.S. has fully vaccinated 59 percent of the country and recorded enough cases to account for 14 percent of the population. (Though, given limited testing, those case numbers almost certainly underestimate true 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 against the coronavirus—from 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 pin down with the data we have. This uncertainty matters because even a small percentage difference in overall immunity translates to a large number of susceptible people. For example, an additional 5 percent of Americans without immunity is 16.5 million people, and 16.5 million additional infections could mean hundreds of thousands more hospitalizations. Because unvaccinated people tend to cluster geographically and because many hospital intensive-care units run close to capacity even in non-pandemic times, it doesn’t take very 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 are more highly vaccinated than the U.S., are already seeing spikes heading into winter. Cases in Germany, which has vaccinated nearly 70 percent of its population, have increased sharply, overwhelming hospitals and spurring renewed restrictions on the unvaccinated. The U.S. does have a bit more immunity from previous infections than Germany because it’s had bigger past COVID waves, but it still has plenty of susceptible people.

The strength of immunity also varies from person to person. Immunity from past infection, in particular, can be quite variable. Vaccine-induced immunity tends to be more consistent, but older people and immunocompromised people mount weaker responses. And immunity against infection also clearly wanes over time in everyone, meaning breakthrough infections are becoming more common. Boosters, which are poised to be available to all adults soon, can counteract the waning this winter, though we don’t yet know how durable that protection will be in the long term. If the sum of all this immunity is on the higher side, this winter might be relatively gentle; if not, we could be in store for yet another taxing surge.

Will New Variants Emerge?

At the beginning of the pandemic, scientists thought that this coronavirus mutated fairly slowly. Then, in late 2020, a more transmissible Alpha variant came along. And then an even more transmissible Delta variant emerged. In a year, the virus more than doubled its contagiousness. The evolution of this coronavirus may now be slowing, but that doesn’t mean it’s stopped: We should expect the coronavirus to keep changing.

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

The Beta and Gamma variants also eroded immune protection, but they weren’t able to compete with the current Delta variant. There may yet be new variants that can. Whether any of this will happen in time to make a difference this winter is impossible to know, but it will happen eventually. This is just how evolution works. Other coronaviruses that cause the common cold also change every year—as does the flu. The viruses are always causing reinfections, but each reinfection also refreshes the immune system’s memory.

A new variant could change the pandemic trajectory again this winter, but it’s not likely to reset the pandemic clock back to March 2020. We might end up with a variant that causes more breakthrough infections or reinfections, but our immune systems won’t be totally fooled.

How Will People Spread the Virus?

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

The Delta wave in the Deep South over the summer, for example, ebbed in the late summer and early fall even though many COVID restrictions didn’t come back. If anything, you might have expected cases to rise at that moment, because schools full of unmasked and unvaccinated children were reopening. So what happened? One possible explanation is that people became more careful with masking and social distancing as they saw cases rising around them. More people in the South did get vaccinated, though the rates still lag behind those in the highly vaccinated Northeast. Are surges “self-limiting because people are modifying their behavior in response to recent surges?” Cobey says. “That’s just a really open question.” Weather may also drive behavior; as temperatures cooled down in the South, people might have spent more time outdoors.

Another possible factor in ending the summer surge is that the virus may have simply infected everyone it could find at the time—but that is not the same as saying it has infected everyone in those states. The coronavirus doesn’t spread evenly across a region, like ink through water. Instead, it has to travel along networks of connection between people. COVID-19 can run through an entire household or workplace, but it can’t jump to the next one unless people are moving in between them. By sheer chance, the coronavirus may find some pockets of susceptible people but not others in any given wave. “There’s a kind of randomness to it,” Zelner says. This winter, we should expect a local flare-up every time the virus finds a pocket of susceptibility. But it’s hard to predict exactly when and where that will happen. The country’s current COVID hot spots are Michigan, Minnesota, and New Mexico, three states with no obvious connection among them.

By winter’s end, the U.S. will emerge with more immunity than it has now—either through infection or, much preferable, through vaccinating more people. “To me, this winter is the last stand,” Zelner says. However these three unknowns play 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.

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