Duration of immune protection of SARS-CoV-2 natural infection against reinfection

Background: The future of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic hinges on virus evolution and duration of immune protection of natural infection against reinfection. We investigated the duration of protection afforded by natural infection, the effect of viral immune evasion on duration of protection and protection against severe reinfection, in Qatar, between 28 February 2020 and 5 June 2022. Methods: Three national, matched, retrospective cohort studies were conducted to compare the incidence of SARS-CoV-2 infection and coronavirus disease 2019 (COVID-19) severity among unvaccinated persons with a documented SARS-CoV-2 primary infection, to incidence among those infection-naive and unvaccinated. Associations were estimated using Cox proportional hazard regression models. Results: Effectiveness of pre-Omicron primary infection against pre-Omicron reinfection was 85.5% [95% confidence interval (CI): 84.8-86.2%]. Effectiveness peaked at 90.5% (95% CI: 88.4-92.3%) in the 7th month after the primary infection, but waned to similar to 70% by the 16th month. Extrapolating this waning trend using a Gompertz curve suggested an effectiveness of 50% in the 22nd month and < 10% by the 32nd month. Effectiveness of pre-Omicron primary infection against Omicron reinfection was 38.1% (95% CI: 36.3-39.8%) and declined with time since primary infection. A Gompertz curve suggested an effectiveness of < 10% by the 15th month. Effectiveness of primary infection against severe, critical or fatal COVID-19 reinfection was 97.3% (95% CI: 94.9-98.6%), irrespective of the variant of primary infection or reinfection, and with no evidence for waning. Similar results were found in sub-group analyses for those >= 50 years of age. Conclusions: Protection of natural infection against reinfection wanes and may diminish within a few years. Viral immune evasion accelerates this waning. Protection against severe reinfection remains very strong, with no evidence for waning, irrespective of variant, for over 14 months after primary infection.