For people who have endured one bout of covid-19, a question looms: How protected are they from bad outcomes if they’re infected again? Not as much as some might think, according to a study from the Department of Veterans Affairs of nearly 41,000 people who suffered reinfection.
Ziyad Al-Aly, one of the study's authors and chief of research and development at the VA St. Louis Health Care System, said a second, third or further infections can lead to health complications just as the first can.
"Getting it a second time is almost like you're trying your chance again with Russian roulette," Al-Aly, who is also a clinical epidemiologist at Washington University, said. "You may have dodged a bullet the first time, but each time you get the infection you are trying your luck again."
The paper, published Thursday in the journal Nature Medicine, involves an analysis of electronic medical records in the VA's national health-care database. It found that patients with reinfections tended to have more complications in various organ systems both during their initial illness and longer term, and they were more likely to be diagnosed with long covid than people who did not get another infection. The findings applied regardless of people's vaccination status or whether they were boosted.
The study included a review of the medical records of 5.8 million patients, 443,588 of whom had been infected once, and 40,947 who had been infected two or more times. The median time between the first and second infection was 191 days. Compared with people who experienced only one infection, those who were reinfected had a twofold increased risk of death, threefold increased risk of hospitalization, twofold increased risk of long covid, threefold increase in risk of heart problems and blood clotting disorders, and twofold increased risk of fatigue.
But the research is just a small part of the story on reinfection and SARS-CoV-2.
When the pandemic began, everyone's immune system started in a similar place of never having encountered the virus. Nearly three years later, some people have been infected and reinfected with different variants and vaccinated and boosted with different products creating great diversity in our immune systems across the world - meaning there are no simple answers to how previous infection will affect someone's response to reinfection. More than 80 percent of Americans are estimated to have been infected with the coronavirus at least once.
Monica Gandhi, an infectious-diseases specialist at the University of California at San Francisco, said it is important to keep in mind that research using electronic medical records "does not reliably predict a causal relationship."
Gandhi pointed to other studies, including one that took a look at 26 studies of reinfections that show they become less severe over time. Another study from Qatar examined patients with different vaccination histories in more comprehensive ways and found that reinfections tend not to progress to severe, critical or fatal outcomes. Those studies have not yet been peer-reviewed.
Gandhi also said there's research showing that infection, reinfection, vaccination and boosting broaden and diversify components of the immune system that may make people "better able to respond to the newest subvariants as we continue to live with covid-19."
William Schaffner, an infectious-diseases specialist at Vanderbilt University Medical Center who was not involved in the study, said the findings are consistent with recent work about the long-term consequences of flu that shows how the virus stimulates an immune response that can "smolder" after the initial illness.
"All these respiratory viruses seem to have long-term effects we have not appreciated in the past," Schaffner said.
Al-Aly said his research began as a way to answer questions asked by patients he saw at the VA in spring 2022 as the omicron variant surged.
"They had been infected before and vaccinated, and they were talking as if they were invincible," Al-Aly said. So he and his colleagues began looking into the question of whether reinfection matters.
"The short answer is: Absolutely. It absolutely does," Al-Aly said.
As we enter a winter when flu, respiratory syncytial virus and coronavirus are circulating, Al-Aly suggested people reconsider what they can do to minimize 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.