“This study’s findings were unanticipated,” says Stanley Perlman, a microbiologist at the University of Iowa’s Roy J. and Lucille A. Carver College of Medicine, in Iowa City, who was not involved in the study. “We would have expected repeat disease to be milder because of immunity from the first infection. Perlman emphasizes that Al-Ali’s results still need to be validated in other populations, and that more research on reinfections is needed, especially among vaccinated people exposed to newer variants. Most hospitalizations and deaths from COVID are occurring among the elderly and in unvaccinated or immunocompromised people, Perlman says. But for people outside those groups, “I think most subsequent infections are milder than the initial ones,” he speculates, but he cautions that there could be unexpected immunological effects occurring that scientists do not understand.
Yet recent data reinforce Al-Ali’s evidence that repeat infections can be severe, while providing new insights into what heightens risks for vulnerable people. A preprint study posted in January (which has not yet been peer-reviewed), for instance, reported that the severity of a person’s initial bout with COVID predicts how severe the disease might be should it strike again. The investigators in this case reviewed electronic health records from a more diverse population of 1.5 million COVID patients treated at U.S. hospitals between March 1, 2020 and July 1, 2022. Nearly 6 percent of these individuals had been infected more than once, and in most cases, the reinfections occurred when the original Omicron variant was spreading (November 2021 to mid-March 2022).
Among those hospitalized with severe COVID the first time around, nearly half were hospitalized again when reinfected. Conversely, roughly 90 percent of people with mild initial infections avoided hospitalization when sickened again with COVID later. Notably, the investigators found that reinfections were also associated with elevated risks of long COVID—lingering symptoms such as fatigue, shortness of breath and brain fog that persist months or years after an initial infection. But the basis for that trend is unclear. There could be biological factors at play, or maybe “doctors are simply documenting a backlog of long COVID with the new diagnostic code, which became available in late 2021,” says Emily Hadley, a data scientist at RTI International, a nonprofit research institute in Durham, N.C., and the study’s first author.
