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Effect of prior SARS-CoV-2 infection on vaccine protection remains poorly understood. Here, we investigated whether persons vaccinated after a prior infection have better protection against future infection than those vaccinated without prior infection. Effect of prior infection was assessed in Qatar population, where the Alpha (B.1.1.7) and Beta (B.1.351) variants dominate incidence, using two national retrospective, matched-cohort studies, one for the BNT162b2 (Pfizer-BioNTech) vaccine, and one for the mRNA-1273 (Moderna) vaccine. Incidence rates of infection among BNT162b2-vaccinated persons, with and without prior infection, were estimated, respectively, at 1.66 (95% CI: 1.26-2.18) and 11.02 (95% CI: 9.90-12.26) per 10,000 person-weeks. The incidence rate ratio was 0.15 (95% CI: 0.11-0.20). Analogous incidence rates among mRNA-1273-vaccinated persons were estimated at 1.55 (95% CI: 0.86-2.80) and 1.83 (95% CI: 1.07-3.16) per 10,000 person-weeks. The incidence rate ratio was 0.85 (95% CI: 0.34-2.05). Prior infection enhanced protection of those BNT162b2-vaccinated, but not those mRNA-1273-vaccinated. These findings may have implications for dosing, interval between doses, and potential need for booster vaccination.

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