Protection of COVID-19 Vaccination Against Hospitalization During the Era of Omicron BA.4 and BA.5 Predominance: A Nationwide Case-Control Study Based on the French National Health Data System

Background Knowing the duration of effectiveness of coronavirus disease 2019 (COVID-19) booster doses is essential to providing decision-makers with scientific arguments about the frequency of subsequent injections. We estimated the level of protection against COVID-19-related hospitalizations (Omicron BA.4-BA.5) over time after vaccination, accounting for breakthrough infections.Methods In this nationwide case-control study, all cases of hospitalizations for COVID-19 identified in the comprehensive French National Health Data System between June 1, 2022, and October 15, 2022, were matched with up to 10 controls by year of birth, sex, department, and an individual COVID-19 hospitalization risk score. Conditional logistic regressions were used to estimate the level of protection against COVID-19-related hospitalizations conferred by primary and booster vaccination, accounting for history of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.Results A total of 38 839 cases were matched to 377 653 controls; 19.2% and 9.9% were unvaccinated, respectively, while 68.2% and 77.7% had received >= 1 booster dose. Protection provided by primary vaccination reached 45% (95% CI, 42%-47%). The incremental effectiveness of booster doses ranged from 69% (95% CI, 67%-71%; <= 2 months) to 22% (95% CI, 19%-25%; >= 6 months). Specifically, the second booster provided an additional protection compared with the first ranging from 61% (95% CI, 59%-64%; <= 2 months) to 7% (95% CI, 2%-13%; >= 4 months). Previous SARS-CoV-2 infection conferred a strong, long-lasting protection (51% >= 20 months). There was no incremental effectiveness of a second booster among individuals infected since the first booster.Conclusions In the era of Omicron BA.4 and BA.5 predominance, primary vaccination still conferred protection against COVID-19 hospitalization, while booster doses provided an additional time-limited protection. The second booster had no additional protection in case of infection since the first booster.