July 7, 2022 – People who become reinfected with the virus that causes COVID-19 face more health risks with each round of reinfection, a large national database survey shows.
Researchers saw worse health effects during active infection, but some symptoms lasted as long as 6 months, suggesting a direct link between reinfection and long-term COVID.
“Re-infection adds or contributes additional health risks. It’s not completely benign and people should try to avoid being re-infected,” said lead study author Ziyad Al-Aly, MD.
The risks persisted whether or not people were fully vaccinated. In some cases, people may have been previously infected with the Delta strain and are now exposed to Omicron or its subvariant, BA.5, which may be better at evading vaccine protection, he says.
“It’s also possible that the first infection 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 Washington University and chief of research and development at the University of Washington. VA St. Louis Health Care System. “There are many variables at play, but it is clear that reinfections carry 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. The information for the study was sourced from veterans in a Department of Veterans Affairs health care database.
The results were published online on June 17 as a pre-print study, meaning it has not yet been peer-reviewed, an important step to help evaluate and validate clinical research. The study is reviewed by the journal Nature portfolio†
Experts weigh in
Three COVID-19 experts not involved in the study made a number of 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, compared with a first, a second infection was associated with twice as many people dying from any cause, and twice the risk of heart or lung problems.
The additional risks also increased with each infection, says Topol, executive vice president of Scripps Research and editor-in-chief of Medscape, WebMD’s sister site for healthcare professionals.
“Clearly, these findings are concerning, because reinfection was quite rare before the Omicron wave hit, at 1% or less through the Delta variant wave. But now, reinfections are much more common,” he says.
Higher risks, especially for some
The study was “well done,” said Ali Mokdad, PhD, when asked to comment. Al-Aly and colleagues “have access to good data and have done several studies.”
He says the additional risks are more likely in the elderly, immunocompromised people, and those with other medical conditions.
“It makes sense, and let me explain why,” Mokdad says. “If you have someone who got COVID-19 the first time and was affected by it, maybe someone who was older or had a chronic condition, the next blow would also do more damage.”
“That’s why you would expect that some people are more likely to have a second infection,” said Mokdad, an adjunct professor of epidemiology and professor of health sciences at the University of Washington in Seattle.
“The best thing for you and for the general public — healthy or not, chronic condition or not — is not to get infected,” he says. “Go get your vaccines and your boosters and wear a mask if you’re in a place that’s crowded and you can’t keep a safe distance.”
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 scientist 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 with risk factors for serious illness,” he says, because veterans tend to be older and have more health problems.
He says many people who get re-infected test positive at home. As a result, their cases fail the investigation. In contrast, the veterans in the study were “people who, for whatever reason, wanted to get a formal test.”
Because the virus has mutated from the vaccines, the injections can still protect against severe illness, hospitalization and death, but they are less able to protect against infection, Adalja says. “That’s also the case with previous immunity. For example, if you were someone who was infected with BA.1 or Delta, your ability to fend off the new variants, BA.4 and BA.5, may not be very high.”
The study shows why “it’s important to stay on top of your vaccines,” he says, “and why we need better vaccines targeting variants 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 long-term effects
Whether reinfection contributes to an increased risk of long-term COVID was unknown, so researcher Al-Aly and colleagues followed the veterans for 6 months. They compared people with one, two, three or more infections to the uninfected group.
Of 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 re-infection had more than double the risk of dying from any cause.
While “the mechanisms underlying the increased risk of death and adverse health outcomes with reinfection are not fully understood,” the authors say, “the findings highlight the consequences of reinfection and emphasize the importance of preventing SARS-CoV reinfection.” -2,” the virus that causes COVID-19.
Asked about the next step in their research, Al-Aly said, “BA.5 seems to be the most important challenge ahead, and we’re focused on trying to understand it better.”