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Scientists want to know if vaccinated people can still become COVID-19 long-haulers

Shots can block hospitalizations, but we don’t know if they prevent chronic symptoms

Illustration by Alex Castro / The Verge

Data from multiple COVID-19 vaccines makes it clear that the shots protect against the most severe outcomes of the disease: hospitalization and death. But it’s still unclear how well the vaccines will reduce the risk of chronic, long-term symptoms, which a small but significant number of COVID-19 patients experience.

“It’s an incredibly important question that we just don’t know the answer to,” says Timothy Henrich, a virologist and viral immunologist at the University of California, San Francisco who is studying the long-term effects of the disease.

The various COVID-19 vaccines tested so far, including those made by Johnson and Johnson, Moderna, Pfizer and BioNTech, and Novavax, are all remarkably consistent in their near-perfect protection against hospitalization and death. These vaccines will be able to relieve pressure on health care systems and slow the overwhelming tally of COVID-19 deaths.

But the vaccines aren’t perfect shields against getting sick with COVID-19. While they turned what may have been some severe cases of the disease into mild ones — a huge victory for public health — a handful of people in the clinical trials still got sick. In addition, it’s still not clear if the vaccines can block infection with the virus entirely or if they’re mainly able to make people asymptomatic.

Scientists don’t know if a muted case of the disease in someone who has been vaccinated would be enough to trigger persistent symptoms. “I think it’s likely that they could,” says Priya Duggal, an epidemiologist at Johns Hopkins, who’s also studying long-term symptoms of COVID-19. Many people who experience chronic symptoms didn’t get seriously sick during their initial infection. “They’re not necessarily hospitalized patients. A number are either asymptomatic or mildly symptomatic in the early phase,” Duggal says.

Researchers still don’t have a good understanding of long-haulers overall. Their symptoms are diverse: some people may have altered taste or smell, while others could have consistent fevers and be short of breath for months. It’s also unclear what causes those symptoms to stick around after the acute phase of the infection.

“There may be several different mechanisms that are going to be causing this to happen,” Henrich says.

One theory is that long-haulers’ immune systems didn’t manage to wipe out the virus completely during their initial infection. Even though the person is no longer infectious, they may still have bits of virus or viral fragments lingering in their body, causing damage. If that is the case, it’s possible that vaccination would prevent that from happening, says Aaron Ring, an immunologist at the Yale School of Medicine. “This is all hypothetical, but a vaccine, which can boost a very effective immune response, could promote more complete viral clearance,” he says. “In theory, if that was the mechanism, it could help prevent some of those symptoms.”

If that isn’t the mechanism, a vaccine might have less of a direct route to preventing those symptoms. Infection might provoke the immune system to attack the body, or the virus that does slip through could damage organs in a way that takes a long time to heal. If someone is vaccinated and still ends up with a mild case of disease, the virus could, in theory, still do that. “Would a vaccine interfere with that, or would a vaccine not interfere with that — that’s not known,” Duggal says.

Duggal and Heinrich are hoping to find answers on the relationship between vaccination and long-haulers through their research on COVID-19 patients. Duggal is running a survey of 25,000 people who’ve had the disease, and it includes a question asking if they’ve been vaccinated or are participating in a vaccine trial.

Heinrich and his team are following people with persistent symptoms over time. “We’re looking for people who have been vaccinated and also become infected,” he says.

Duggal isn’t sure vaccines will reduce the risk for persistent symptoms entirely. “I think there is going to be a small percentage of people that could get infected even post-vaccination that could become long-haulers,” she says.

To be clear, it’s not likely that vaccination, by converting severe cases of COVID-19 to mild cases, will create more long-haulers, says Jessica Dine, a pulmonary specialist at the University of Pennsylvania Perelman School of Medicine. “That’s not what we typically observe with other vaccines,” she says. “With the flu shot, you can still get the flu, even though you’ll get a milder case. But we don’t see an increase in stuff like post-viral inflammation.”

Dine’s best guess is that we’ll see fewer people with long-term symptoms as more people get vaccinated. Right now, the percentage of people who get COVID-19 and end up with long-term symptoms is fairly high — some estimates put it around 10 percent, with others going higher. Duggal also hopes vaccination could cut that number down. “If people are vaccinated, can we drop that number to one to five percent? Can we get it lower? I’m hoping that’s what it is,” she says. “I just don’t know, but I’m hoping it’ll be fewer people.”

In the meantime, the researchers stress that there’s a clear way vaccines will reduce the number of long-haulers: by driving down the number of infections in the population overall. “As more people get vaccinated, there’s less virus circulating,” Duggal says. That means fewer people getting sick, which leads to fewer people experiencing long-term symptoms.

“If we’re going to ever try to reach this mountain of herd immunity, people have to get vaccinated,” she says. “If we can do that, we’re also protecting ourselves.”