Patients who previously had Covid-19 appeared to have a lower risk of contracting Covid-19 from the delta variant than those who received Pfizer-BioNTech's Covid-19 vaccine alone, according to a preprint study from Israel published in medRxiv. However, the authors and other health experts caution the study comes with some significant limitations.

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Study details

For the retrospective, observational study, researchers analyzed data from Maccabi Healthcare Services' database in Israel. The study population consisted of three groups: individuals fully vaccinated with Pfizer-BioNTech in January or February; unvaccinated people, who had previously been infected with Covid-19 in January or February; and previously infected people who had also been at least partially vaccinated, including some who received just one dose of the vaccine at least seven days before the study period.

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Overall, the study population included almost 674,000 fully vaccinated people who had not been previously infected. Meanwhile, among those who had previously had Covid-19, around 63,000 were unvaccinated and 42,000 had received one dose of a Covid-19 vaccine.

The participants were monitored for symptoms, infections, and hospitalizations from June to August, around the time the delta variant surged in Israel.

Key findings

After adjusting for age, sex, socioeconomic status, and comorbidities, the researchers found that those who were fully vaccinated with the Pfizer-BioNTech Covid-19 vaccine had a 13.06-fold increased risk of developing Covid-19 from the delta variant than those who had previously had Covid-19.

In addition, the researchers found that people in the study fully vaccinated with the Pfizer-BioNTech vaccine were also at a 27-fold increased risk of developing symptomatic Covid-19 compared to those who previously had Covid-19 developing symptomatic reinfection, the study found.

However, the researchers said the evidence suggested that natural immunity appeared to wane over time. Specifically, according to the researchers, when compared to those who were infected prior to February 2021, those who were fully vaccinated had a 5.96-fold increased risk of developing a breakthrough infection and 7.13-fold increased risk for symptomatic disease.

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The study also found that those who previously had Covid-19 saw more protection against reinfection from a single dose of Pfizer's Covid-19 vaccine compared to those who had had a prior infection and remained unvaccinated.

The researchers also noted that there were no Covid-related deaths in the study.

Authors, experts preach caution in interpreting results

However, the researchers cautioned about extrapolating their results. They said since the delta variant was the most common cause of infection among participants in the study, the study results cannot be translated to other variants of the virus. They also said the findings may have underestimated asymptomatic cases, and that the findings can only be limited to the Pfizer-BioNTech vaccine.

In addition, while the study's researchers say this is the largest real-world comparison of Covid-19 immunity derived from natural infection versus vaccination, Charlotte Thålin, a physician and immunology researcher at Danderyd Hospital and the Karolinska Institute, cautioned that many of the numbers used in the study were still "small."

For example, she pointed out that the higher rate of hospitalization found within an analysis of 32,000 study participants was based on just eight hospitalizations within the vaccinated group and one hospitalization among the previously infected group. Similarly, the researchers calculated the 13-fold increased risk of infection based on just 238 infections among about 16,000 vaccinated people—accounting for less than 1.5% of that group—versus 19 reinfections among roughly 16,000 study participants who had been previously infected.

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In addition, Robert Schooley, from the University of California, San Diego, reiterated the authors' caution that the findings should be interpreted carefully because they likely underestimate the number of people with asymptomatic Covid-19.

In the study, Covid-19 infection was detected via a PCR test, and those with asymptomatic Covid-19 are typically less likely to get tested. Therefore, the study results could have been skewed toward patients with symptomatic Covid-19, Schooley said.

"The more symptomatic your infection is, the more likely you are to mount a brisk immune response," he said.

Moreover, experts pointed out that no one in the study passed away, which they said clearly demonstrates that the vaccine offers strong protection against serious infection.

Experts also cautioned that the study shouldn't encourage people to intentionally get Covid-19.

While the study shows the benefits of natural immunity, it "doesn't take into account what this virus does to the body to get to that point," Marion Pepper, an immunologist at the University of Washington, Seattle, said.

"Unvaccinated people who get infected are where we see the deaths occurring," Schooley said. "Putting yourself at risk of dying to have 'natural' immunity is not a great tradeoff."

Alessandro Sette, from the La Jolla Institute for Immunology, added that the study findings "should not be interpreted as saying, 'if you have already been infected, don't get vaccinated.'"

"People who have been infected still get a benefit—for themselves and for society—by getting vaccinated, and one shot of a vaccine is sufficient to achieve that," Sette said. (D'Ambrosio, MedPage Today, 8/28; Wadman, Science Magazine, 8/26)