Will Omicron Leave Most of Us Immune?

Even before Omicron hit the United States in full force, most of our bodies had already wised up to SARS-CoV-2’s insidious spike—through infection, injection, or both. By the end of October 2021, some 86.2 percent of American immune systems may have glimpsed the virus’s most infamous protein, according to one estimate; now, as Omicron adds roughly 800,000 known cases to the national roster each day, the cohort of spike-zero Americans, the truly immunologically naive, is shrinking fast. Virginia Pitzer, an epidemiologist at Yale’s School of Public Health and one of the scientists who arrived at the 86.2 percent estimate, has a guess for what fraction of the U.S. population will have had some experience with the spike protein when the Omicron wave subsides: 90 to 95 percent.

The close of Omicron’s crush, then, should bring the country one step closer to hitting a COVID equilibrium in which SARS-CoV-2’s still around, but disrupting our lives far less. In the most optimistic view of our future, this surge could be seen as a turning point in the country’s population-level protection. Omicron’s reach could be so comprehensive that, as some have forecasted, this wave ends up being the pandemic’s last.

Read: The worst of the Omicron wave could still be coming

But there is reason to believe that this ultra-sunny forecast won’t come to pass. “This wave will not be the last,” Shane Crotty, of the La Jolla Institute of Immunology, told me. “There are not many things that I am willing to be pretty confident about. But that’s one of them.” A new antibody-dodging variant, for one, could still show up to clobber us. And nearly everyone having some form of spike in their past isn’t as protective as it might sound. In a few months’ time, American immune systems will be better acquainted with SARS-CoV-2’s spike than they’ve ever been. But 90 to 95 percent of people exposed doesn’t translate to 90 to 95 percent protected from ever getting infected or sick again; more immune doesn’t have to mean immune enough. By the time the country exits this wave, each of our bodies will be in radically different immunological spots—some stronger, some weaker, some fresher, some staler. Chart that out by demography and geography, and the defensive matrix only gets more complex: Certain communities will have built up higher anti-COVID walls than others, which will remain relatively vulnerable. The malleability of the virus and the United States’ patchwork approach to combatting it has always meant that COVID would spread unevenly. Now the sums of those decisions will be reflected by our immunity. They’ll dictate how our next tussle with the virus unfolds—and who may have to bear the brunt of it.

Collective immunity is the key to ending a pandemic. But its building blocks start with each individual. By now we know that immunity against the coronavirus isn’t binary—and while no one can yet say exactly how much more protection Person A (triple vaxxed, recently infected) might have than Person B (twice infected, once vaxxed) or Person C (once infected, never vaxxed), we have figured out some of the broad trends that can toggle susceptibility up or down. Allowing for shades of gray, a person’s current immune status hinges on “the number of exposures [to the spike protein], and time since last exposure,” John Wherry, an immunologist at the University of Pennsylvania, told me. Infections and vaccinations add protection; time erodes it away.

Part of this boils down to relatively basic arithmetic. Each exposure to SARS-CoV-2’s spike protein, whether through injection or infection, can be expected to build iteratively on the quantity, quality, and durability of the body’s defenses The more intensely and more frequently the body is bothered, the more resources it will invest to fend off that same threat. While a duo of vaccines, for instance, isn’t enough to reliably guard against less severe Omicron cases, a trio of shots seems to do the trick for most. It also pays to pace encounters judiciously. Crowd the second and third too close together, for instance, and the latter’s effect may be blunted; a several-months-long wait, meanwhile, can supercharge the body’s response by allowing immune cells sufficient time to mull what they’ve learned.

The contents of an exposure can matter too, though immunologists still debate the protective merits of tossing a dangerous, bona fide virus into the mix. Infections can blitz a smorgasbord of proteins from a currently circulating variant into the airway, tickling out immune defenses that in-the-arm, spike-centric vaccines don’t reliably rouse—but they can also, you know, cause COVID, and leave wildly inconsistent levels of protection behind. “It’s really not worth the risk,” Taia Wang, an immunologist at Stanford, told me. Those who already have both types of spike exposures in their history, though, seem to reap some of the relative benefits of each—the two stimuli synergize, and patch each other’s gaps. Post-vaccination Omicron infections, in particular, could awaken immune cells that didn’t respond to the original-recipe spike, broadening the range of defenders available for future fights.

Read: Should I just get Omicron over with?

Neither virus-induced immunity nor vaccine-induced immunity against infection seems to last terribly long, however. (Protection against severe disease, at least, has been quite a bit more stubborn, and some experts hold out hope that additional doses or infections might eventually get our defenses against milder cases to hold as well.) For now, people who have logged only a solo encounter with SARS-CoV-2’s spike, or are many months away from their last viral brush, can reasonably assume that they’re vulnerable to infection again. The fewer past brushes with spike, the speedier that relapse will be, too. Responses might be especially ephemeral in certain people, including older or immunocompromised individuals, whose immune systems aren’t easily tickled by vaccines.

But it’s not always obvious why people respond differently to the same viruses or shots. Even within a demographic group, “some people generate really robust responses, and others just never do,” Wang told me. Projections based on a vaccine dosing schedule, or someone’s infection history, aren’t a surefire bet. All of this underlies, then, the massive disconnect between previously exposed and currently protected, Joshua Salomon, a health-policy researcher at Stanford who’s collaborating with Pitzer to model Omicron’s immunological impact, told me. Salomon, Pitzer, and their colleagues estimate that although a significant majority of Americans had rendezvoused with the spike protein by October’s end, fewer than half were still reasonably well guarded against a future infection. (Most retained resilience against severe disease.) People who enter the “well defended” group can also exit it, and join the susceptibles again.

Two years, 530 million vaccine doses, and 68 million documented SARS-CoV-2 infections deep into the pandemic, the range of vulnerability in our population has never been larger or more unwieldy. Some high-risk people, never vaccinated or infected, have essentially no protection to speak of; many young, healthy individuals have been triply vaccinated, and are fresh off an Omicron breakthrough. “That’s a huge, huge range,” Wang told me, with a chasm of immunological possibility in between. And none of this accounts for the very real risk that another wonky and wily variant, distinct from Omicron and everything else we’ve seen before, could still upend every rosy immunological assumption we lay down, and send us into yet another devastating surge.

And when new variants show up, they will once again reveal the cracks and crevices where protection is lacking. In the same way that single individuals with different exposure histories can’t be expected to achieve the same levels of immune protection, neither can communities with different pandemic histories. Fresh, good-quality immunity simply won’t distribute evenly—we’re likely to see islands, separated by immense seas. Many of these differences will tie straight back to “how inequitably we distributed vaccines,” Elaine Hernandez, a health demographer at Indiana University at Bloomington, told me. Through first, second, and now third doses, we’ve managed to concentrate immune protection among the privileged. Shots remain proportionally sparse in poor communities, rural communities, low-resource communities; unvaccinated people also “tend to concentrate geographically,” Anne Sosin, a health-equity researcher at Dartmouth, told me, seeding fertile ground for the virus to fix in a population and spread. To date, there are still plenty of “pockets that may have not yet had exposure to vaccination or the virus,” Bertha Hidalgo, an epidemiologist at the University of Alabama at Birmingham, told me.

Read: It’s a terrible idea to deny medical care to unvaccinated people

After flitting through urban centers, Omicron will find these isolated enclaves. It will pummel them. It will cause debilitating disease and death, but generate perhaps only a flimsy veneer of protection that, unbuttressed by vaccines, might not successfully ward off future waves. By one estimate, a third to half of all Americans may end up infected by Omicron by mid-February. The variant will not encounter all of those people on equal immunological footing, nor will it create such footing. “Some people will be left with immune houses of straw, others of wood, others of brick,” Sosin said. The virus is not an equalizer; it never has been.

Appending vaccinations on top of recent Omicron infections in less protected places could help even the playing field—but there may not be incentive to, as Omicron cases eventually fall away. In many parts of the country where vaccinations have struggled to gain traction, “there is a predominant belief that infection means you are now immune, especially if you were quite sick,” Hidalgo told me. If uptake of shots continues to be sluggish, the gaps in protection that existed before Omicron only stand to widen. This is the texture that national curves and figures obscure: knots of vulnerability that many Americans can easily ignore, but that the virus all too easily exploits.

Read: Our relationship with COVID vaccines is just getting started

Omicron’s cross-country sweep won’t amount to nothing. Immunity will be raised, on average, and “we can still expect it to add friction” to any future path the virus takes, Sarah Cobey, an infectious-disease modeler at the University of Chicago, told me. This may well be the last COVID surge that plays out in such a staggering fashion. We may, for a time, get a touch of reprieve. Even if a new antibody-dodging variant screeches onto the scene, there are “limitations to how this virus can evolve,” Marion Pepper, an immunologist at the University of Washington, told me. By this point, perhaps many immune systems will have seen enough to anticipate what hijinks the virus lobs at us next.

But future surges of infection will still carry their own problems. They may be more complicated to track, because they are more local; more asynchronous, because outbreaks will start and end at different times; more patchwork, because of the “communities I worry we’ve left behind,” Sosin told me. As immunity ebbs and flows, our fates will continue to splinter, at the level of both individual and population alike. And yet, our geographies are not so divided that the pathogen won’t pass between them. When the threat is this infectious, it’s not our immunological differences that define us, but the common ground we offer the virus when we allow it to spread.