A study published Wednesday in the New England Journal of Medicine suggests that the amount of protection an individual's natural immunity offers against reinfection depends on which variant the individual is exposed to.

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Study details and key findings

For the study, researchers in Qatar performed a test-negative case-control study using data from Qatar's national SARS-CoV-2 databases to determine "the proportional reduction in susceptibility to infection" among individuals who had recovered from previous coronavirus infections and those who had not been infected.

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Researchers only included cases with a cycle threshold (Ct) of 30 or less, to ensure that only "epidemiologically relevant reinfections were considered." With a median age of 31 to 35 years, the study's population was young, but still representative of Qatar's total population.

In the analysis, case patients were defined as individuals with positive PCR results, and controls were defined as individuals with negative PCR results. Both groups were matched according to sex, 10-year age group, nationality, and calendar time of PCR testing to account for known differences in the risk of being infected with the coronavirus in Qatar.

Among cases and controls, the median interval between previous infection and PCR testing was 279 days for analysis of the alpha variant, 285 days for analysis of the beta variant, 254 days for analysis of the delta variant, and 314 days for analysis of the omicron variant.

Researchers estimated that the effectiveness of previous infection in preventing reinfection was 90.2% against subsequent exposure to the alpha variant, 85.7% against the beta variant, 92% against the delta variant, and 56% against the omicron variant.

The researchers separately adjusted for vaccination status, excluding vaccinated patients from the analysis, and found roughly similar rates of protection.

In addition, none of the reinfections resulted in death, and researchers estimated that the effectiveness of natural infection against "severe, critical, or fatal" coronavirus infection overall was 69.4% against the alpha variant, 88% against beta, 100% against delta, and 87.8% against omicron. 

While the researchers acknowledged that the study was limited by its young population, they concluded that "protection of previous infection against hospitalization or death caused by reinfection appeared to be robust, regardless of variant," and even through protection against reinfection with the omicron variant was "lower," they noted that it was "still considerable."

Natural immunity is still not the preferred choice in combatting future infection

Because Covid-19 emerged just two years ago, there's still little real-world evidence on the durability of natural immunity to reinfection—and natural immunity may fade relatively quickly.

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According to Eli Rosenberg, deputy director for science at the New York State Department of Health, "the totality of the evidence suggests … that both vaccination and having survived Covid each prove protection against subsequent infection and hospitalization." However, "only one of those is the safe choice that we would recommend," he added. "And that's vaccination."

"The bottom line message is that from symptomatic Covid infection you do generate some immunity," said E. John Wherry, an immunologist at the University of Pennsylvania. "But it's still much safer to get your immunity from vaccination than from infection."

Vaccination following prior infection from Covid-19 has long been recommended because both natural and vaccine-induced immunity eventually wane. In addition, much still isn't known about natural immunity, particularly from an infection from a long time ago, said Ali Ellebedy, an immunologist at Washington University in St. Louis.

"There are so many variables you cannot control that you just cannot use [prior natural infection] as a way to say, 'Oh, I'm infected then I am protected,'" Ellebedy said. (Altarawneh et al., New England Journal of Medicine, 2/9; Walker, MedPage Today, 2/9)