Time-Dependent Changes in Death Reports and the Sex Ratio in the Safety Surveillance of SARS-CoV-2 Vaccination in Japan, the United States, and European Countries

Abstract

The national safety surveillance of vaccines is a fundamental measure to ensure vaccination safety and maintain transparency and public trust. Our previous study revealed an early increase in death reports after the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination in Japanese surveillance despite our hypothesis that no time-dependent variations in the number of death reports would be seen if the vaccination is not related to serious adverse events. This study is an extensive investigation to determine whether the number of death reports varied consistently over time after vaccination in the older population in Japan, the US, and European countries. We collected the death reports after BNT162b2 mRNA vaccination in individuals aged 65 years or older using the open databases in Japan, the US (Vaccine Adverse Event Reporting System, VAERS), and European countries (EudraVigilance). We observed an early increase of death reports on Day 2 after the vaccination in all three databases. The female-to-male ratio was also assessed and showed a certain degree of time-dependence ( R 2 of linear regression 0.54, p =0.01) in Japan but not in the US and European countries. The findings suggest the existence of unknown predictors of the adverse events of the SARS-CoV-2 vaccination, especially for the older Japanese population. The continuous and careful monitoring safety aspects of the vaccines are warranted.

Analysis of the Association Between BNT162b2 mRNA COVID-19 Vaccination and Deaths Within 10 Days After Vaccination Using the Sex Ratio in Japan

“…The accumulation of these outcomes may have resulted in a lower sex ratio during the risk period for all-cause deaths. As Yamashita et al indicated in 2022, the reasons for the low sex ratios are believed to be that women's body weight in Japan is generally lower than that in the USA and European countries [4] and that women's immune responses to vaccines are stronger than those of men [7]. No significant differences were observed between the sex ratios by period across any of the outcomes.…”

“…The author believes that the SCRI may have the same advantage. Yamashita et al stated in their paper, "we evaluated if the death reports would show the uneven distribution after vaccination" [4]. To the author's knowledge, the SCRI and the method of comparing sex ratios have not been discussed in terms of incidentality or even distribution.…”

“…In contrast, Yamashita et al reported in 2022 time-dependent changes in the sex ratio of deaths after the BNT162b2 mRNA vaccination, a COVID-19 vaccination, in Japan. Specifically, there was a significant difference in the sex ratio between the period within 10 days after vaccination and that after 11 days in the reported deaths after vaccination among individuals aged ≥65 years [4]. This indicates that the vaccination may influence the occurrence of death within the initial 10 days after vaccination.…”

“…This indicates that the vaccination may influence the occurrence of death within the initial 10 days after vaccination. This 10-day period was chosen due to the higher frequency of reported deaths during this timeframe [4].…”

Importance of Examining Incidentality in Vaccine Safety Assessment

“…In addition to the SCRI, another method to examine incidentality is to compare sex ratios by period [11,14]. In this method, the sex ratios during the risk period are compared with those during the control period.…”