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

Abstract

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 (VEOxford/AstraZeneca = 0.592 [0.518–0.655], VEJanssen = 0.754 [0.628–0.838], VEModerna = 0.573 [0.526–0.615], VEPfizer-BioNTech = 0.487 [0.461–0.513], VESinopharm = 0.530 [0.496–0.561], and VESputnik 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.

A safety study evaluating non-COVID-19 mortality risk following COVID-19 vaccination

“…A recent study in Hungary demonstrated the effectiveness of COVID-19 vaccination in reducing all-cause mortality after adjusting for measured confounders and potential healthy vaccinee effect when compared to unvaccinated individuals. [37] A VSD study found that the mortality rates were lower in the days immediately following vaccination in a cohort of adults and children between January 1, 2005 and December 31, 2008, indicating a healthy vaccinee effect. [38] Another VSD study included individuals aged 9 to 26 years with deaths between January 1, 2005 and December 31, 2011.…”

Effect of Age, Sex, and COVID-19 Vaccination History on All-Cause Mortality: Unexpected Outcomes in a Complex Biological and Social System

“…They argue for performing RCTs of mRNA and adeno-vectored vaccines head-to-head comparing long-term effects on overall mortality [151]. The study of Ben et al [155] confirms the results of the much larger Hungarian study which contained over 6 million participants after exclusion of partly vaccinated individuals [156].…”

“…Hence, while this view is interesting it is mixing time-dependent changes. However, note that outcomes >21 days ago are generally worse than their <21 days counterpart -although highly age dependent, seemingly an outcome of vaccine waning which is especially rapid in the mRNA vaccines [40]. However, the principle of using shape profiles has been demonstrated.…”

“…Firstly, a Hungarian study with comprehensive risk adjustment showed that the magnitude and post vaccination trajectory of all-cause survival after COVID-19 vaccination varied markedly between COVID vaccine manufacturers [156].…”

“…Taking survival at 21 days during the epidemic period (April to June 2021), which is the break point in the ONS vaccination data for England [43], all vaccines deliver protection, however all-cause survival is highest for Janssen (viral vector) followed equally by Sputnik and AstraZeneca (both viral vector). Next is Sinopharm (inactivated whole virus) and then lowest protection equally by Moderna and Pfizer (both mRNA) [156] However, 80-day survival during the epidemic period) was highest for Janssen (viral vector), Sputnik (viral vector) and AstraZeneca (viral vector). Moderna (mRNA) had a worse all-cause mortality outcome than the unvaccinated, while Pfizer (mRNA) was equal to the unvaccinated, while Sinopharm (inactivated whole virus) was slightly better than the unvaccinated [156].…”