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A prior infection from COVID-19 was more protective than vaccine-induced immunity in reducing the risk of infection and symptomatic illness from the Delta variant, according to a retrospective observational study from Israel.

Those who received both doses of the Pfizer/BioNTech vaccine in January or February of this year had a 13.06-fold increased risk (95% CI 8.08-21.11) of SARS-CoV-2 infection with the Delta variant compared to those who had COVID-19 during the same time period, reported Sivan Gazit, MD, MA, of Maccabi Healthcare Services in Tel Aviv, and colleagues.

Vaccine-induced immunity was also associated with a 27-fold increased risk for symptomatic infection (95% CI 12.7-57.5) compared with symptomatic reinfection (P<0.001), the researchers wrote in a paper published on the preprint server , which has not undergone peer-review.

Among people with prior infection, a single dose of the vaccine conferred more protection against reinfection compared with no vaccination at all (OR 0.53, 95% CI 0.3-0.92).

But experts cautioned that these results shouldn't encourage people to go out and get infected. Robert Schooley, MD, of the University of California San Diego, told MedPage Today that waiting around to get infected with the hopes of gaining natural immunity puts people at risk of infection without a baseline level of protection.

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

Schooley also noted that these findings are limited due to a potential underestimate of asymptomatic infections. COVID-19 infections in this study were detected upon health visits via PCR testing. Because people with asymptomatic infection are typically less likely to get a test, this study may have been skewed more towards symptomatic patients.

"The more symptomatic your infection is, the more likely you are to mount a brisk immune response," Schooley pointed out.

This was the largest real-world study to compare immunity to SARS-CoV-2 derived from natural infection versus vaccination, the researchers said.

The retrospective study used a large healthcare database in Israel and included patients ages 16 and older in three groups: SARS-CoV-2-naive individuals who were fully vaccinated; previously infected people who were unvaccinated; and previously infected people who received a single dose of the vaccine. Vaccination or infections occurred in January or February. Patients were followed from June to August -- the same time as the surge of cases from the Delta variant in Israel.

The researchers adjusted for covariates including age, sex, socioeconomic status, and comorbidities, including cardiovascular disease, hypertension, diabetes, kidney disease, obstructive pulmonary disease, immunocompromised conditions, and cancer.

Nearly 674,000 fully vaccinated people were included in the study. In the groups with previous infection, about 63,000 were unvaccinated, and 42,000 had received one dose.

Natural immunity appeared more protective against hospitalization, with eight hospitalizations in the vaccine immunity cohort, and one in the natural immunity cohort.

In a separate analysis that compared vaccine and natural immunity regardless of the time of infection, fully vaccinated patients had a higher risk of infection (OR 5.96, 95% CI 4.85-7.33) and symptomatic disease (OR 7.13, 95% CI 5.51-9.21).

There were no COVID-related deaths reported in any of the cohorts.

Because the Delta variant was the most common source of infection during the study period, these results cannot be translated to immunity against other strains, Gazit's group said. Additionally, they recognized that this study may have underestimated asymptomatic cases, and that the findings do not apply to those who received a vaccine other than Pfizer's.

Alessandro Sette, DSc, of the La Jolla Institute for Immunology in California, who was not involved in this study, emphasized that these 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 vaccine is sufficient to achieve that," Sette said. (CDC recommends a two-dose series for the mRNA vaccines or the single-shot Johnson & Johnson vaccine regardless of prior infection status.)

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