Effectiveness of a second BNT162b2 booster vaccine against hospitalization and death from COVID-19 in adults aged over 60 years.

The rapid emergence of the B.1.1.529 (Omicron) variant of SARS-CoV-2 led to a global resurgence of coronavirus disease 2019 (COVID-19). Israeli authorities approved a fourth COVID-19 vaccine dose (second booster) for individuals aged 60 years and over who had received a first booster dose 4 or more months earlier. Evidence for the effectiveness of a second booster dose in reducing hospitalizations and mortality due to COVID-19 is warranted. This retrospective cohort study included all members of Clalit Health Services who were aged 60-100 years and who were eligible for the second booster on 3 January 2022. Hospitalizations and mortality due to COVID-19 in participants who received the second booster were compared with those for participants who received one booster dose. Cox proportional hazards regression models with time-dependent covariates were used to estimate the association between the second booster and hospitalization and death due to COVID-19 while adjusting for demographic factors and coexisting illnesses. A total of 563,465 participants met the eligibility criteria. Of those, 328,597 (58%) received a second booster dose during the 40 day study period. Hospitalization due to COVID-19 occurred in 270 of the second-booster recipients and in 550 participants who received one booster dose (adjusted hazard ratio, 0.36; 95% confidence interval (CI): 0.31-0.43). Death due to COVID-19 occurred in 92 second-booster recipients and in 232 participants who received one booster dose (adjusted hazard ratio, 0.22; 95% CI: 0.17-0.28). This study demonstrates a substantial reduction in hospitalizations and deaths due to COVID-19 conferred by a second booster in Israeli adults aged 60 years and over.