July 7, 2022 — People who are reinfected with the virus that causes COVID-19 face more health risks with each round of reinfection, a large national database study finds.
The researchers saw worse health effects during active infection, but some symptoms lasted up to 6 months, suggesting a direct link between reinfection and long-lasting COVID.
“Reinfection adds or contributes to additional health risks. It’s not entirely good, and people should try to avoid reinfection,” says lead study author Ziyad Al-Aly, MD.
The risks remained whether or not people were fully vaccinated. In some cases, people may have been infected earlier with the Delta strain and now be exposed to Omicron or its subvariant, BA.5, which may be better at evading vaccine protection, he says.
“It is also possible that the first infection may have weakened some organ systems and made people more vulnerable to health risks when they get a second or third infection,” adds Al-Aly, a clinical epidemiologist at the University of Washington and chief of research and development at the VA Health Care System St. “There are many variables at play, but it is clear that reinfections contribute additional risks and should be avoided.”
Al-Aly and his colleagues compared 257,427 people with a first infection with the virus that causes COVID-19 with a group of 38,926 people who had a second or later infection, and then with 5.4 million people who were never infected. . Information for the study came from veterans in a Department of Veterans Affairs health care database.
The results were published online June 17 as a preprint study, meaning it has not yet been peer-reviewed, a key step to help evaluate and validate clinical research. The study is under review by the journal Nature’s Portfolio.
Experts weigh in
Three COVID-19 experts who were not involved in the research raised several caveats, including how a study of veterans may or may not apply to the general population.
“It’s the first study to characterize the risks of reinfection,” says Eric Topol, MD.
He points out that a second infection, compared to a first, was associated with twice the rate of people dying from any cause, as well as twice the risk of heart or lung problems.
Additional risks also increased with each infection, says Topol, executive vice president of Scripps Research and editor-in-chief for Medscape, WebMD’s sister site for health care professionals.
“Obviously these findings are concerning as reinfection was quite rare before the Omicron wave hit, at 1% or less through the Delta variant wave. But now reinfections have become much more common,” he says.
Higher risks, especially for some
The study was “well done,” says Ali Mokdad, PhD, when asked for comment. Al-Aly and colleagues “have access to good data and have done some studies.”
He says additional risks are more likely in the elderly, the immunized and people with other medical conditions.
“It makes sense, and let me explain why,” says Mokdad. “When you have someone who was infected with COVID-19 the first time and was affected by it, maybe someone who was older or who had a chronic condition, the next hit will cause even more damage.”
“That’s why you would expect some people to be more likely to have a second, more difficult infection,” says Mokdad, an assistant professor of epidemiology and professor of health measurement sciences at the University of Washington in Seattle.
“The best thing for you and the general public — healthy or not, chronic condition or not — is not to get infected,” he says. “Go get your shots and boosters and wear a mask when you’re in a crowded place and you can’t keep a safe distance.”
Are Veterans’ Risk Factors Different?
“When you look at that study, the big caveat is that veterans are not like the general population,” says Amesh Adalja, MD, a senior researcher at the Johns Hopkins Center for Health Security at the Bloomberg School of Public Health in Baltimore.
“I don’t think you can generalize [the study] for everyone, but really for people who have risk factors for serious illness,” he says, because veterans tend to be older and have more health conditions.
He says many people who get reinfected are testing positive at home. As a result, their cases are not included in the search. In contrast, the veterans in the study were “people who for whatever reason wanted to take an official test.”
Since the virus has mutated away from vaccines, vaccines can still protect against severe illness, hospitalization and death, but they are less able to protect against infection, Adalja says. “This is also the case with previous immunity. If you were someone infected with BA.1 or Delta, for example, your ability to avoid the new variants, BA.4 and BA.5, may not be very high .”
The study shows why “it’s important to stay up to date with your vaccines,” he says, “and why we need to get better vaccines that target the variants that are currently circulating.”
Despite these caveats, Adalja says, the researchers used “a robust database” and a large study population, which “gives us all confidence in the strength of the finding.”
Looking at the long-term effects
It was not known whether reinfection contributes to the increased risk of long-term COVID, so researcher Al-Aly and colleagues followed the veterans for 6 months. They compared people who had one, two, three or more infections with the uninfected group.
Among those with reinfection, about 13% had two infections, 0.76% had three infections, and 0.08%, or 246, people had four or more infections.
Compared to veterans with a first coronavirus infection, those who got a reinfection had more than twice the risk of dying from any cause.
Although “the mechanisms underpinning the increased risks of death and adverse health outcomes in reinfection are not entirely clear,” say the authors, “the findings highlight the consequences of reinfection and emphasize the importance of preventing SARS-CoV-2 reinfection.” the virus that causes COVID-19.
Asked about the next step in their research, Al-Aly said: “BA.5 seems to be the main challenge ahead and we are focused on trying to better understand it.”