The question of what “infection” means is just one of the riddles posed by the late-stage pandemic.

Date:   8/23/2021 1:48:07 AM ( 3 y ago)

Have You Already Had a Breakthrough COVID Infection?
The question of what “infection” means is just one of the riddles posed by the late-stage pandemic.

By Dhruv Khullar
August 22, 2021
People walking on a street in Provincetown.
More than a thousand cases have been linked to an outbreak this summer in Provincetown, Massachusetts; still, there have been just seven hospitalizations and no deaths.
** Photograph by Barry Chin / Boston Globe / Getty

For most of the year, Provincetown, Massachusetts, on the northern tip of Cape Cod, has around three thousand residents. In summertime, however, it becomes a vacation destination and gay mecca. Thousands of visitors typically descend for festivals, concerts, parades, comedy shows, and parties organized around themed weeks. Almost all of this has been suspended during the pandemic; in June, Provincetown didn’t record a single coronavirus case. Then, in early July, thousands of gay men arrived for Circuit Party week. The crowds thrummed with a sense of post-pandemic exuberance. The weather was rainy, and people squeezed into indoor venues “to the point you could hardly move,” one reveller, from Ohio, told the Washington Post. Another, speaking with NPR, recalled that it would “get so incredibly hot in these clubs that you would just be wet with sweat, so you’d have to step outside for a moment just to get a breath of fresh air.”

Not long afterward, dozens of attendees developed symptoms of COVID-19. Investigators from the Centers for Disease Control and Prevention quickly identified four hundred and sixty-nine new cases among Massachusetts residents. Almost all of the infections were due to the highly contagious Delta variant, and nearly three-quarters occurred in vaccinated people. By mid-July, the test-positivity rate in Provincetown had soared to over fifteen per cent. Perhaps the most concerning finding about the outbreak was that, judging by their nasal swabs, vaccinated and unvaccinated people were harboring similar levels of the virus. To some, this discovery suggested that immunized individuals might spread Delta more readily than previously thought; it prompted the C.D.C. to recommend that all Americans, regardless of vaccination status, resume wearing masks in public, indoor spaces when in locales with “substantial” or “high” COVID transmission. (According to the agency’s definition, those designations apply to more than ninety per cent of counties in the U.S.)
Read The New Yorker’s complete news coverage and analysis of the coronavirus pandemic.

Many people heard about these findings late last month, when they appeared on slide seventeen of an internal document from the C.D.C., which was widely published in newspapers. The deck contained a few other concerning messages—that some thirty-five thousand vaccinated people experience symptomatic coronavirus infections each week; that the proportion of vaccinated individuals hospitalized with COVID-19 has increased; that the Delta variant likely inflicts more severe disease than its predecessors. A single phrase in the deck was quoted in headlines: “The war has changed.”

Even before Americans learned of the Provincetown outbreak, nearly two-thirds said that they were worried about the rise of Delta. Vaccinated people were much more likely to express concern—a sign that fear of breakthrough infection was starting to puncture the promise of post-pandemic life. Since then, American optimism has cratered, with a forty-nine-point drop in the number of survey respondents who say that our situation is getting better. We’re now more pessimistic about COVID-19 than at any point since January, when we were in the midst of the nation’s deadliest weeks.

But to what degree has the war really changed? How much do we actually know about breakthrough infections and their possible dangers? Understanding the risks is not easy. The lockdown mind-set, despite its obvious drawbacks, was cognitively simple; life in the liminal state asks us to carry a heavier mental load. This is especially true because the term “breakthrough infection” is vague. A breakthrough infection could be an illness that knocks you flat, a tickle in your nose, or nothing. Regular reports of breakthroughs suggest that we should be scared. But what exactly should we be scared of?

In one sense, defining a breakthrough infection is straightforward: you have one if you test positive two or more weeks after completing all recommended doses of a COVID vaccine. But, in another sense, the meaning of the term is unclear. A highly sensitive P.C.R. test has detected some of the virus’s genetic code inside your nose. So what?

“Your body doesn’t produce infinite amounts of antibodies,” Angela Rasmussen, a virologist at the Vaccine and Infectious Disease Organization who studies the push and pull between hosts and pathogens, told me. “Your lymph nodes are not, like, the horn of plenty.” It’s possible to be exposed to more virus than the antibodies in your nose can handle. Still, Rasmussen said, “When you’ve been immunized and get an ‘infection’ ”—she raised her hands in scare quotes—“or, I should say, when you test positive by P.C.R.—that doesn’t mean there’s a robust viral infection raging in your body. Even if some cells do get infected, other parts of the immune system spring into action and stop it from spreading.” She went on, “Is that an infection? That’s a philosophical question. Technically, some cells got infected and the virus started to replicate. But the immune system prevented you from getting sick and shedding copious amounts of virus that can go on to infect someone else.”

Rasmussen thinks that, when it comes to asymptomatic or mildly symptomatic cases, the term “breakthrough infection” is somewhat misleading. “It doesn’t describe how vaccines work very well,” she said. In such cases, the vaccines have actually succeeded, and there’s no meaningful sense in which the virus has broken through. Instead of using the breakthrough metaphor, Rasmussen suggests imagining an encounter between two armies. “The immune system has multiple specialized units that can be deployed strategically and dynamically,” she said. “The virus has some tricks up its sleeve, but, compared to the human immune system, it doesn’t have as much at its disposal. It’s like ‘Lord of the Rings’ or ‘Troy’: one army usually kicks the other’s ass. If you’re vaccinated, your immune system is ready, it’s better equipped, and it usually kicks the virus’s ass.”

But not always. In some cases, the virus gains a foothold, multiplies, and challenges even a primed immune system, inflicting real disease—a true breakthrough. Michel Nussenzweig, a molecular immunologist at Rockefeller University, told me that three main factors influence the course of events. First, there are your antibody levels; second, there’s your antibodies’ affinity for a particular variant; and, third, there’s the amount of virus to which you’ve been exposed. Whether a small viral incursion escalates into a major battle depends on how those factors combine.

Antibody levels rise and fall: right after infection or vaccination, B cells in our blood produce huge numbers of them, but, as the months pass, antibody levels decline. The key question is how these declines affect the course of a coronavirus infection. Declines might make it easier for the virus to establish a foothold in your body, but not necessarily translate into a substantial weakening of your immunity. Nussenzweig pointed me to a recent study done in Australia. The researchers found that, when a vaccinated person’s antibody levels fall to around twenty per cent of the typical post-infection level, protection against symptomatic infection drops to fifty per cent. Protection against severe disease, however, doesn’t fall to fifty per cent until antibodies wane to just three per cent of post-infection levels.

From The New Yorker

 

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