Senior Researcher Section of Clinical Epidemiology, Department of Data Science, Center for Clinical Sciences, National Center for Global Health and Medicine, Tokyo, Japan Shinjuku-ku, Japan
Background: A total of 1,962 deaths had been reported as suspected to be related to mRNA COVID-19 vaccines until December 18, 2022. However, a causal relationship between the COVID-19 vaccines and death has not been confirmed. Studies that assessed the mortality following the vaccination are limited in Japan. Therefore, evaluating the risk of death after the mRNA COVID-19 vaccination is necessary.
Objectives: To assess the risk of mortality after the mRNA COVID-19 vaccine (BNT162b2 or mRNA-1273) in Japan.
Methods: We performed a nested-case control study among adults ≥18 years using data between January 1, 2019 and April 13, 2022 from one municipality in the Vaccine Effectiveness, Networking, and Universal Safety Study. We defined February 17, 2021, the date on which the COVID-19 vaccination program started in Japan, as the cohort entry date (CED). We included individuals: 1) aged ≥18 years on February 1, 2021 and 2) confirmed any medical histories before the CED. We excluded individuals: 1) died, moved from the municipality, or were not resident before the CED; 2) with COVID-19 before the CED. We followed up from the CED to the date that met the following criteria, whichever came fast: died, moved, developed COVID-19, or end of the study period. The cases were identified by death records. The controls were matched with a 1:5 ratio by age (five-year groups) and sex using risk-set sampling. The death date and matched date was defined as the index date. The exposures were defined by the vaccination of the mRNA COVID-19 vaccines (BNT162b2 or mRNA-1273). We set exposures as each first, second, and third dose within 0–21 days and 0–42 days before the index date. We used a conditional logistic regression model to estimate the odds ratios (OR) and 95% confidence interval (95% CI). We included Charlson comorbidities in the model as covariates.
Results: Among 475,323 individuals between January 1, 2019 and April 13, 2022 in the municipality, 134,328 were included in the study. During the follow-up period, we identified 4,247 (3.5%) cases in 148,746 person-year; and 4,246 cases (median age [IQR], 85 [79, 90]; 48.1% were women) and 21,230 controls (median age [IQR], 85 [79, 90]; 48.1% were women) were matched by the risk-set sampling. The adjusted ORs (95% CI) of mortality for the first, second, and third doses within 0–21 days before the index date were 0.30 (0.23–0.38), 0.36 (0.29–0.46), and 0.36 (0.28–0.45), respectively. The ORs of the first, second, and third doses within 0–42 days were 0.50 (0.42–0.60), 0.44 (0.37–0.53), and 0.30 (0.25–0.36), respectively.
Conclusions: The results did not show an increase in the mortality risk after mRNA COVID-19 vaccines (first, second, or third doses) among individuals ≥18 years in Japan.
