The Incidence of SARS-CoV-2 Reinfection in Persons With Naturally Acquired Immunity With and Without Subsequent Receipt of a Dose of BNT162b2 Vaccine

Background: There is insufficient evidence regarding the magnitude and durability of protection conferred by a com-bined effect of naturally acquired immunity after SARS-CoV-2 infection and vaccine-induced immunity. Objective: To compare the incidence rate of SARS-CoV-2 reinfection in previously infected persons to that of previ-ously infected persons who subsequently received a single dose of BNT162b2 messenger RNA vaccine. Design: A retrospective cohort study emulating a random-ized controlled target trial through a series of nested trials. Setting: Nationally centralized database of Maccabi Healthcare Services, Israel. Participants: Persons 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. Intervention: Forty-one randomized controlled trials were emu-lated, in which 107413 Maccabi Healthcare Services' members aged 16 years and older were eligible for at least 1 trial. Measurements: SARS-CoV-2-related outcomes of infection, symptomatic disease, hospitalization, and death, between 2 March and 13 December 2021. Results: A 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 com -pared with those who were not vaccinated after infection. No COVID-19-related mortality cases were found. Limitation: Hybrid protection against non-Delta variants could not be inferred. Conclusion: Persons 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, reinfec-tion appeared relatively rare. Primary Funding Source: None. Ann Intern Med. 2022;175:674-681. doi:10.7326/M21-4130 Annals.org For author, article, and disclosure information, see end of text. This article was published at Annals.org on 15 February 2022.