July 7, 2022 — People who are reinfected with the virus that causes COVID-19 face more health risks with each cycle of reinfection, a large national database study finds.
The researchers observed worse health outcomes during active infection, but some symptoms persisted for up to 6 months, suggesting a direct link between re-infection and persistent COVID.
“Reinfection adds or contributes to additional health risks. It’s not entirely benign, and people should try to avoid reinfection,” said lead study author Ziyad Al-Ali, MD.
The risks remain whether people have been fully vaccinated or not. In some cases, people may have been previously infected with the Delta strain and now be exposed to Omicron or its BA.5 subvariant, 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 got a second or third infection,” adds Al-Ali, a clinical epidemiologist at the University of Washington and head of research and development. at VA St. Louis Health Care System. “There are many variables, but it is clear that re-infections contribute additional risks and should be avoided.”
Al-Ali 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 have never been infected. Information for the study came from veterans in a Department of Veterans Affairs health database.
The results were published online June 17 as a pre-print study, meaning it has not yet been peer-reviewed, a key step to help evaluate and validate clinical research.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 Natural portfolio.
Experts weigh in
Three experts on COVID-19 who were not involved in the study raised several caveats, including how a study of veterans may or may not apply to the general population.
“This is the first study to characterize the risks of re-infection,” says Dr. Eric Topol.
He points out that a second infection, compared to a first, is associated with twice the rate of people dying from any cause, and twice the risk of heart or lung problems.
The additional risks become greater with each infection, says Topol, executive vice president of Scripps Research and editor-in-chief of Medscape, WebMD’s sister site for health professionals.
“Obviously these findings are troubling, as re-infection was quite rare before the Omicron wave hit, at 1% or less during the Delta Variant wave. But now re-infections have become much more common,” he says.
Higher risks, especially for some
The study was “well done,” said Dr. Ali Mokdad, when asked for comment. Al-Ali and his colleagues “have access to good data and have done several studies.”
He says additional risks are more likely among the elderly, the immunocompromised and people with other medical conditions.
“It makes sense, and let me explain why,” Mokdad says. “When you have someone who got COVID-19 for the first time and was affected by it, maybe someone who was older or had a chronic illness, the next exposure would also cause more damage.”
“That’s why you would expect some people to have a more severe second infection,” said Mokdad, assistant professor of epidemiology and professor of health indicators at the University of Washington in Seattle.
“The best thing for you and the general public—healthy or not, chronic 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 can’t keep a safe distance.”
Are risk factors different for veterans?
“When you look at this study, the big caveat is that veterans are not like the general population,” said Amesh Adalya, 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 who have risk factors for severe disease,” he says, because veterans tend to be older and have more health problems.
He says many people who get re-infected have a positive test at home. As a result, their cases do not fall under 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 vaccines can still protect against severe illness, hospitalization and death, but they are less able to protect against infection, Adalya says. “This is also the case with previous immunity. If you were someone infected with BA.1 or Delta, for example, your ability to fend off the new variants, BA.4 and BA.5, might not be very high.”
The study shows why “it’s important to keep up with your vaccines,” he says, “and why we need to get better vaccines that target variants that are currently circulating.”
Despite these caveats, Adalya 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
It was not known whether re-infection contributed to an increased risk of prolonged COVID, so researcher Al-Ali 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 re-infection, 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 re-infected had more than twice the risk of dying from any cause.
Although “the mechanisms underlying the increased risks of death and adverse health outcomes in reinfection are not entirely clear,” the authors say, “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-Ali said: “BA.5 seems to be the main challenge ahead and we are focused on trying to understand it better.”