Your Vaccinated Immune System Is Ready for Breakthroughs

Getting COVID-19 when you’re vaccinated isn’t the same as getting COVID-19 when you’re unvaccinated.

Art of immune cells flexing
Adam Maida / The Atlantic

A new dichotomy has begun dogging the pandemic discourse. With the rise of the über-transmissible Delta variant, experts are saying you’re either going to get vaccinated, or going to get the coronavirus.

For some people—a decent number of us, actually—it’s going to be both.

Coronavirus infections are happening among vaccinated people. They’re going to keep happening as long as the virus is with us, and we’re nowhere close to beating it. When a virus has so thoroughly infiltrated the human population, post-vaccination infections become an arithmetic inevitability. As much as we’d like to think otherwise, being vaccinated does not mean being done with SARS-CoV-2.

Post-vaccination infections, or breakthroughs, might occasionally turn symptomatic, but they aren’t shameful or aberrant. They also aren’t proof that the shots are failing. These cases are, on average, gentler and less symptomatic; faster-resolving, with less virus lingering—and, it appears, less likely to pass the pathogen on. The immunity offered by vaccines works in iterations and gradations, not absolutes. It does not make a person completely impervious to infection. It also does not evaporate when a few microbes breach a body’s barriers. A breakthrough, despite what it might seem, does not cause our defenses to crumble or even break; it does not erase the protection that’s already been built. Rather than setting up fragile and penetrable shields, vaccines reinforce the defenses we already have, so that we can encounter the virus safely and potentially build further upon that protection.

To understand the anatomy of a breakthrough case, it’s helpful to think of the human body as a castle. Deepta Bhattacharya, an immunologist at the University of Arizona, compares immunization to reinforcing such a stronghold against assault.

Without vaccination, the castle’s defenders have no idea an attack is coming. They might have stationed a few aggressive guard dogs outside, but these mutts aren’t terribly discerning: They’re the system’s innate defenders, fast-acting and brutal, but short-lived and woefully imprecise. They’ll sink their teeth into anything they don’t recognize, and are easily duped by stealthier invaders. If only quarrelsome canines stand between the virus and the castle’s treasures, that’s a pretty flimsy first line of defense. But it’s essentially the situation that many uninoculated people are in. Other fighters, who operate with more precision and punch—the body’s adaptive cells—will eventually be roused. Without prior warning, though, they’ll come out in full force only after a weeks-long delay, by which time the virus may have run roughshod over everything it can. At that point, the fight may, quite literally, be at a fever pitch, fueling worsening symptoms.

Vaccination completely rewrites the beginning, middle, and end of this story. COVID-19 shots act as confidential informants, who pass around intel on the pathogen within the castle walls. With that info, defensive cells can patrol the building’s borders, keeping an eye out for a now-familiar foe. When the virus attempts to force its way in, it will hit “backup layer after backup layer” of defense, Bhattacharya told me.

Prepped by a vaccine, immune reinforcements will be marshaled to the fore much faster—within days of an invasion, sometimes much less. Adaptive cells called B cells, which produce antibodies, and T cells, which kill virus-infected cells, will have had time to study the pathogen’s features, and sharpen their weapons against it. While the guard dogs are pouncing, archers trained to recognize the virus will be shooting it down; the few microbes that make their way deeper inside will be gutted by sword-wielding assassins lurking in the shadows. “Each stage it has to get past takes a bigger chunk out” of the virus, Bhattacharya said. Even if a couple particles eke past every hurdle, their ranks are fewer, weaker, and less damaging.

In the best-case scenario, the virus might even be instantly sniped at by immune cells and antibodies, still amped up from the vaccine’s recent visit, preventing any infection from being established at all. But expecting this of our shots every time isn’t reasonable (and, in fact, wasn’t the goal set for any COVID-19 vaccine). Some people’s immune cells might have slow reflexes and keep their weapons holstered for too long; that will be especially true among the elderly and immunocompromised—their fighters will still rally, just to a lesser extent.

Changes on the virus side could tip the scales as well. Like invaders in disguise, wily variants might evade detection by certain antibodies. Even readily recognizable versions of the coronavirus can overwhelm the immune system’s early cavalcade if they raid the premises in high-enough numbers—via, for instance, an intense and prolonged exposure event.

With so many factors at play, it’s not hard to see how a few viral particles might still hit their mark. But a body under siege isn’t going to throw its hands up in defeat. “People tend to think of this as yes or no—if I got vaccinated, I should not get any symptoms; I should be completely protected,” Laura Su, an immunologist at the University of Pennsylvania, told me. “But there’s way more nuance than that.” Even as the virus is raising a ruckus, immune cells and molecules will be attempting to hold their ground, regain their edge, and knock the pathogen back down. Those late-arriving efforts might not halt an infection entirely, but they will still curb the pathogen’s opportunities to move throughout the body, cause symptoms, and spread to someone else. The inhospitality of the vaccinated body to SARS-CoV-2 is what’s given many researchers hope that long COVID, too, will be rarer among the immunized, though that connection is still being explored.

Breakthroughs, especially symptomatic ones, are still uncommon, as a proportion of immunized people. But by sheer number, “the more people get vaccinated, the more you will see these breakthrough infections,” Juliet Morrison, a virologist at UC Riverside, told me. (Don’t forget that a small fraction of millions of people is still a lot of people—and in communities where a majority of people are vaccinated, most of the positive tests could be for shot recipients.) Reports of these cases shouldn’t be alarming, especially when we drill down on what’s happening qualitatively. A castle raid is worse if its inhabitants are slaughtered and all its jewels stolen; with vaccines in place, those cases are rare—many of them are getting replaced with lighter thefts, wherein the virus has time only to land a couple of punches before it’s booted out the door. Sure, vaccines would be “better” if they erected impenetrable force fields around every fortress. They don’t, though. Nothing does. And our shots shouldn’t be faulted for failing to live up to an impossible standard—one that obscures what they are able to accomplish. A breached stronghold is not necessarily a defeated stronghold; any castle that arms itself in advance will be in a better position than it was before.

There’s a potential silver lining to breakthroughs as well. By definition, these infections occur in immune systems that already recognize the virus and can learn from it again. Each subsequent encounter with SARS-CoV-2 might effectively remind the body that the pathogen’s threat still looms, coaxing cells into reinvigorating their defenses and sharpening their coronavirus-detecting skills, and prolonging the duration of protection. Some of that familiarity might ebb with certain variants. But in broad strokes, a post-inoculation infection can be “like a booster for the vaccine,” Su, of the University of Pennsylvania, told me. It’s not unlike keeping veteran fighters on retainer: After the dust has settled, the battle’s survivors will be on a sharper lookout for the next assault. That’s certainly no reason to seek out infection. But should such a mishap occur, there’s a good chance that “continuously training immune cells can be a really good thing,” Nicole Baumgarth, an immunologist at UC Davis, told me. (Vaccination, by the way, might mobilize stronger protection than natural infection, and it’s less dangerous to boot.)

We can’t control how SARS-CoV-2 evolves. But how disease manifests depends on both host and pathogen; vaccination hands a lot of the control over that narrative back to us. Understanding breakthroughs requires some intimacy with immunology, but also familiarity with the realities of a virus that will be with us long-term, one that we will probably all encounter at some point. The choice isn’t about getting vaccinated or getting infected. It’s about bolstering our defenses so that we are ready to fight an infection from the best position possible—with our defensive wits about us, and well-armored bodies in tow.