A study published Thursday in Nature Medicine found that Covid-19 patients with reinfections are more likely to be diagnosed with long Covid and experience health complications, including death, heart problems, blood-clotting disorders, and more.

Study details and key findings

To determine whether Covid-19 reinfection increases the health risks associated with an initial infection, researchers analyzed data from over 5 million patients in the US Department of Veterans Affairs' (VA) electronic health care database.

The researchers found that 443,588 patients had experienced one Covid-19 infection, and 40,947 patients were infected at least twice. Of those in the second group, 37,997 (92.8%) patients had two infections, 2,572 (6.3%) patients had three infections, and 378 (0.9%) had four or more infections. On average, participants had around 191 days between their first and second infection and 158 days between their second and third infection.

Compared with individuals who were only infected once, participants who were reinfected experienced a two-fold increase in the risk of death, long Covid, and fatigue, and a three-fold increase in the risk of hospitalization, heart problems, and blood clotting.

The study found an increased risk of complications across all patients, regardless of vaccination status. The risks of complications, including pulmonary, cardiovascular, hematological, diabetes, gastrointestinal, kidney, mental health, musculoskeletal, and neurological disorders, were most prevalent during an active infection—but they lingered six months after infection.

According to Ziyad Al-Aly, study author and chief of research and development at the VA St. Louis Health Care System, the research shows that reinfections can result in health complications just like an initial infection.

"Getting it a second time is almost like you're trying your chance again with Russian roulette," Al-Aly said. "You may have dodged a bullet the first time, but each time you get the infection you are trying your luck again."

Commentary

According to William Schaffner, an infectious-diseases specialist at Vanderbilt University Medical Center who was not involved in the study, the study's findings align with recent research on the long-term effects of flu infections that demonstrates how the virus can stimulate an immune response that can "smolder" after an initial infection.

"All these respiratory viruses seem to have long-term effects we have not appreciated in the past," Schaffner said.

Still, Monica Gandhi, an infectious-diseases specialist at the University of California, San Francisco, noted that it is important to remember that research using EMRs "does not reliably predict a causal relationship."

However, Gandhi also pointed to other research suggesting that reinfections tend to get less severe over time, and that infection, reinfection, vaccination, and boosting increase and diversify the parts of the immune system that can help people become "better able to respond to the newest subvariants as we continue to live with covid-19."

According to Al-Aly, the research aimed to answer questions VA patients asked during the spring 2022 omicron surge. During that time, Al-Aly—and many of his colleagues—noticed that patients seemed to believe that an infection lowered their risk of complications from a reinfection.

"They had been infected before and vaccinated, and they were talking as if they were invincible," Al-Aly said. They decided to investigate whether Covid-19 reinfections can lead to an increased risk of complications.

"The short answer is: Absolutely. It absolutely does," Al-Aly said.

In the coming months, with flu, respiratory syncytial virus, and Covid-19 circulating, Al-Aly encouraged people to take steps to lower their risk of infection.

"I'm not advocating for lockdown or any draconian measures, but I feel if you are boarding a plane, for example, to see your family for Thanksgiving, well, wear that mask as it will protect you and those around you," he said. (Cha, Washington Post, 11/10; Bowe et al., Nature Medicine, 11/10)