• Sivan Gazit, Roei Shlezinger, Galit Perez, Roni Lotan, Asaf Peretz, Amir Ben-Tov, Esma Herzel, Hillel Alapi, Dani Cohen, Khitam Muhsen, Gabriel Chodick, and Tal Patalon.
• Kahn Sagol Maccabi (KSM) Research & Innovation Center and Maccabitech Institute for Research and Innovation, Maccabi Healthcare Services, Tel Aviv, Israel (S.G., T.P.).
• Ann. Intern. Med. 2022 May 1; 175 (5): 674-681.

BackgroundThere is insufficient evidence regarding the magnitude and durability of protection conferred by a combined effect of naturally acquired immunity after SARS-CoV-2 infection and vaccine-induced immunity.ObjectiveTo compare the incidence rate of SARS-CoV-2 reinfection in previously infected persons to that of previously infected persons who subsequently received a single dose of BNT162b2 messenger RNA vaccine.DesignA retrospective cohort study emulating a randomized controlled target trial through a series of nested trials.SettingNationally centralized database of Maccabi Healthcare Services, Israel.ParticipantsPersons with documented SARS-CoV-2 infection who did not receive subsequent SARS-CoV-2 vaccination were compared with persons with documented SARS-CoV-2 infection who received a single dose of the BNT162b2 vaccine at least 3 months after infection.InterventionForty-one randomized controlled trials were emulated, in which 107 413 Maccabi Healthcare Services' members aged 16 years and older were eligible for at least 1 trial.MeasurementsSARS-CoV-2-related outcomes of infection, symptomatic disease, hospitalization, and death, between 2 March and 13 December 2021.ResultsA statistically significant decreased risk (hazard ratio, 0.18 [95% CI, 0.15 to 0.20]) for reinfection was found among persons who were previously infected and then vaccinated versus those who were previously infected but remained unvaccinated. In addition, there was a decreased risk for symptomatic disease (hazard ratio, 0.24 [CI, 0.20 to 0.29]) among previously infected and vaccinated persons compared with those who were not vaccinated after infection. No COVID-19-related mortality cases were found.LimitationHybrid protection against non-Delta variants could not be inferred.ConclusionPersons previously infected with SARS-CoV-2 gained additional protection against reinfection and COVID-19 from a subsequent single dose of the BNT162b2 vaccine. Nonetheless, even without a subsequent vaccination, reinfection appeared relatively rare.Primary Funding SourceNone.

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