The study, which is based on the health records of more than 5.6 million people treated in the VA Health System, found that, compared to those with just one Covid-19 infection, those with two or more documented infections had more than twice the risk of dying and three times the risk of being hospitalized within six months of their last infection. They also had higher risks for lung and heart problems, fatigue, digestive and kidney disorders, diabetes and neurologic problems.
BA.5 carries key mutations that help it escape antibodies generated by both vaccines and prior infection, leaving many people vulnerable to reinfection.
“If you asked me about reinfection maybe a year and a half ago, I would tell you that maybe I have a patient here or there, but it’s really, really rare,” Al-Aly said. That’s not true anymore, though.
“So we asked a simple question that if you got Covid before and now you’re on your second infection, does this really add risk? And the simple answer is that it does.”
Tallying the risks of reinfections
Al-Aly and his team compared the health records of more than 250,000 people who had tested positive for Covid-19 one time with records from 38,000 others who had two or more Covid-19 infections documented in their medical records. More than 5.3 million people with no record of a Covid-19 infection were used as the control group.
Among those with reinfections, 36,000 people had two Covid-19 infections, roughly 2,200 had caught Covid-19 three times, and 246 had been infected four times.
Common new diagnoses after reinfections included chest pain, abnormal heart rhythms, heart attacks, inflammation of the heart muscle or the sac around the heart, heart failure and blood clots. Common lung issues included shortness of breath, low blood oxygen, lung disease, and accumulation of fluid around the lungs, Al-Aly said.
The study found that the risk of a new health problem was highest around the time of a Covid-19 reinfection, but it also persisted for at least six months. The increased risk was present whether or not someone had been vaccinated, and it was graded – meaning it increased with each subsequent infection.
Al-Aly said that’s not what people really think will happen when they get Covid a second or third time.
“There is this idea that if you had Covid before, your immune system is trained to recognize it and is more equipped to fight it, and if you’re getting it again, maybe it does not affect you that much, but that’s not really true, “he said.
Al-Aly said that does not mean there aren’t people who have had Covid and done just fine; there are lots of them. Rather, what his study shows is that each infection brings new risk, and that risk adds up over time, he said.
Even if a person has half the risk of developing lasting health problems during a second infection than they did during their first infection, he said, they still wind up with 50% more risk of problems than someone who did not get Covid-19 a second time.
The study has some important caveats. Al-Aly says it was more common to see reinfections among people who had existing risks because of their age or underlying health. That shows that reinfection may not be random, and it could be that the health risks linked to reinfections aren’t, either.
“It is possible that sicker individuals or people with immune dysfunction are at higher risk of reinfection and adverse health outcomes after reinfection,” Al-Aly said.
He was not interested in trying to isolate the pure effects of reinfection but wanted to understand how repeated infections are affecting the people who get them.
“The most relevant question to people’s lives is, if you get reinfected, does it add to your risk of acute complications and long covid, and the answer is a clear yes and yes,” he said.
The study is observational, which means it can not determine cause and effect.
Al-Aly says the researchers saw these increased risks even after they weighted the data to account for the effects of age, sex, medication use and the person’s underlying health before they got Covid-19.
Covid-19 continues to surprise
Experts who were not involved in the research say it is compelling.
“There is this idea that I think a lot of people have that ‘if I survived my first infection, that I’m really going to be just fine the second time. There really shouldn’t be any problem,'” said Dr. Daniel Griffin, an instructor in clinical medicine at Columbia University.
“The popular wisdom, right, is that reinfections are mild, nothing to worry about, nothing to see here,” Griffin said of the study on the podcast “This Week in Virology.” But that’s not really being born out, he said.
This is not how it’s supposed to work. Even when viruses shape-shift – as influenza does – our immune system generally retains its memory of how to recognize and fight off some part of them. They may still make us ill, but the idea is that our prior immunity is there to mount some kind of defense and keep us from serious harm.
With coronaviruses, and especially SARS-CoV-2 coronaviruses, the hits just keep on coming.
“A year later, you can get reinfected with the same coronavirus the second time. It is not clear that that second infection can be more mild, because coronaviruses intrinsically have the ability to interfere with long-lasting lifetime immunity,” Griffin told CNN.
Griffin says he’s seen Covid-19 reinfections go both ways. Sometimes, the second or third is milder for his patients, but sometimes it’s not.
How does that compare with other respiratory infections?
Early in the pandemic, people would get Covid, and three months would go by when they were pretty well protected, he said. But now, those reinfections are happening more frequently, no doubt because of the rapid changes to the virus. He says he’s seen some people infected four times in the past two years.
“We don’t really see much of that with the flu,” Griffin said.
As for what people should be doing now with regard to this risk, Dr. Michael Osterholm, who directs the Center for Infectious Disease Research and Policy at the University of Minnesota, says Americans are really done with the pandemic. That does not mean that the pandemic is done with us, though.
Osterholm said he has three close friends who recently went to a restaurant for the first time since the pandemic started. All of them tested positive within 72 hours of that restaurant visit.
If you’re at higher risk of serious illness or you just want to avoid getting sick, it’s a good time to be wearing an N95 mask in public places, he says.
“People do not want to hear it, but that’s the reality. We’re seeing this resurgence, and we’re seeing increasing numbers of vaccine failures. Clearly, that’s a major concern,” he said.
CNN Health’s Deidre McPhillips contributed to this report.