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Getting COVID-19 today is much less scary and more common than it was three years ago. By now, many people have had it not just once, but two, three, or even more times. Most of the time, repeat infections aren’t as severe as they were the first time, leading to a sense of complacency about getting COVID-19 over and over.

But reinfections aren’t harmless. As cases continue to rise and more variants arrive on the scene, infectious-disease experts are warning that repeat infections could have cumulative, lasting effects.

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“There is some early evidence starting to show that if you had COVID-19, there can be all sorts of problems after getting infected” and reinfected, says Dr. Robert Murphy, professor of medicine and executive director of the Havey Institute for Global Health at Northwestern’s Feinberg School of Medicine. “We are just at the beginning of learning about them.”

A higher risk of Long COVID

Dr. Ziyad Al-Aly, assistant professor of medicine at Washington University School of Medicine in St. Louis and director of the clinical epidemiology center at the VA St. Louis Health Care System, studies Long COVID: a condition marked by health effects that linger after infection. “Reinfection remains consequential,” he says.

In a paper published in Nature Medicine in 2022, he found that people who had gotten COVID-19 at least twice experienced higher rates of short- and long-term health effects, including heart, lung, and brain issues, compared to those who were only infected once.

But why? Dr. Davey Smith, a virologist and head of infectious diseases at University of California San Diego, says that certain characteristics—such as older age—may make people more vulnerable to complications after repeat bouts. “The older you get, the worse you do with viruses in general, but specifically with SARS-CoV-2,” he says. “Every time you get COVID-19 again and again, you increase the likelihood of having a worse infection just based on age.”

Underlying health conditions that people may not necessarily be aware of—like prediabetes or increased inflammation—could also put them at higher risk after each infection. “For somebody who is already on the edge of developing diabetes and then gets COVID-19, that could damage the pancreas and the endocrine system enough to change things,” Smith says. Similarly, having high rates of inflammation before COVID-19 could raise the risk of heart events such as stroke or a heart attack after an infection.

Regardless of a person’s health status, each COVID-19 infection can raise the risk of developing blood clots, which can travel to the brain or lungs. That’s why Smith believes anyone who is eligible for antiviral drugs such as Paxlovid should take them, since controlling the virus as quickly as possible can reduce any potential long-term or lingering effects an infection can have on the body.

COVID-19 may alter the immune response

At this point, many people view COVID-19 as relatively benign. But even if you’ve already recovered from a mild case, there’s no guarantee that next time will go as smoothly. “Just because you did okay with it last year doesn’t mean you’ll do okay with it this year,” Smith says.

“There is a mischaracterization in the public understanding that you can get an acute infection with fever, cough, malaise, and fatigue, get over it after a few days or a week or so, then bounce back, and it’s gone,” says Al-Aly. “The data are showing that [some] people still display increased risk of problems even two years after an infection.”

That’s what he found in his study. People who had multiple infections were three times more likely to be hospitalized for their infection up to six months later than those who only got COVID-19 once, and were also more likely to have problems with clotting, gastrointestinal disorders, kidney, and mental-health symptoms. The risks appeared to increase the more infections people experienced.

Understanding why SARS-CoV-2 has a uniquely lasting effect on the body remains a challenge. Historically, when the immune system meets a new pathogen like a virus, it generates novel defenses and remembers the intruder, so it has a head start if the virus returns. That’s certainly the case with SARS-CoV-2—which is why vaccines work, and why getting reinfected generally leads to milder symptoms.

But there is also growing evidence that in some people, getting COVID-19 the first time may compromise the immune response in a way that makes the body less likely to respond effectively the next time it sees the virus. That could leave certain organs and body systems, such as the brain, weaker for months after infection—and subsequent ones. “It’s the balance of these two opposing forces—the immune system learning from the past and knowing how to deal with a virus and do a better job the second and third time around, and the idea that a first encounter with a virus might alter the immune system in some way that it becomes less efficient—that could explain why some people get Long COVID,” says Al-Aly.

Data also continue to show that even vaccinated people can get Long COVID—although the risk may be lower—since the protection provided by vaccines wanes over time, just as it does from infections. Vaccines are therefore a strong but not absolute barrier to the virus.

Preventing reinfections

“Each time you get hit, it does impact your body, so let’s try not to get it too many times,” says Smith. That’s easier said than done, since after three years, people are tired of taking precautions such as wearing masks and avoiding crowded public spaces. “We’ve lost the public-health battle; there is no appetite for public masking or stringent public health measures,” says Al-Aly.

That means other strategies need to become available, including universal vaccines that can protect against multiple variants and nasal spray vaccines that stand guard at the nose, which is where SARS-CoV-2 generally enters. Researchers are currently testing these next generation shots, so while “the good news is that these technologies do exist, they need to be accelerated and brought to market as soon as possible to protect the public,” says Al-Aly.

In the meantime, Smith says it’s important for people to understand that they still need to do everything they can to avoid getting COVID-19. That means staying up to date with vaccinations and taking some basic precautions, such as wearing high-quality masks indoors when cases are high, especially in crowded places and on public transportation.

“I wish we lived in a world where getting repeat infections doesn’t matter,” says Al-Aly, “but the reality is that‘s not the case.”

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