Effectiveness of COVID-19 Vaccination in Preventing All-Cause Mortality among Adults during the Third Wave of the Epidemic in Hungary: Nationwide Retrospective Cohort Study

Our investigation aimed to describe the all-cause mortality rates by COVID-19 vaccination groups in Hungary for an epidemic period (1 April 2021–20 June 2021) and a nonepidemic period (21 June 2021–15 August 2021), and to determine the vaccines’ effectiveness in preventing all-cause mortality utilizing nonepidemic effectiveness measures to adjust for the healthy vaccinee effect (HVE). Sociodemographic status, comorbidity, primary care structural characteristics, and HVE-adjusted survival difference between fully vaccinated and unvaccinated cohorts in the epidemic period had been computed by Cox regression models, separately for each vaccine (six vaccines were available in Hungary). Hazard ratio (HR) reduction in epidemic period corrected with nonepidemic period’s HR with 95% confidence interval for each vaccine was used to describe the vaccine effectiveness (VE). The whole adult population (N = 6,404,702) of the country was followed in this study (4,026,849 fully vaccinated). Each vaccine could reduce the HVE-corrected all-cause mortality in the epidemic period (VE(Oxford/AstraZeneca) = 0.592 [0.518–0.655], VE(Janssen) = 0.754 [0.628–0.838], VE(Moderna) = 0.573 [0.526–0.615], VE(Pfizer-BioNTech) = 0.487 [0.461–0.513], VE(Sinopharm) = 0.530 [0.496–0.561], and VE(Sputnik) (V) = 0.557 [0.493–0.614]). The HVE-corrected general mortality for COVID-19 vaccine cohorts demonstrated the real-life effectiveness of vaccines applied in Hungary, and the usefulness of this indicator to convince vaccine hesitants.