SARS-CoV-2 vaccine and increased myocarditis mortality risk: A population based comparative study in Japan

ABSTRACT Objective To investigate the association between SARS-CoV-2 vaccination and myocarditis death Design Population based comparative mortality study Setting Japan Participants Vaccinated population was 99 834 543 individuals aged 12 years and older who have been received SARS-CoV-2 vaccine once or twice by 14 February 2022. Reference population was defined persons aged 10 years and older from 2017 to 2019. Main outcome measures The primary outcome was myocarditis death, defined as the case with “myocarditis” for primary cause of death and with onset 28 days or less after vaccination disclosed on 11 November 2022. Myocarditis mortality rate ratio (MMRR) of the SARS-CoV-2 vaccinated to the reference population by 10-year age group and standardised mortality ratio (SMR) were calculated. Mortality odds ratios (MORs) by 10-year age group were also calculated for supplementary analysis. Healthy vaccine effect-adjusted MMRRs (adMMRRs) or adjusted SMR (adSMR) were calculated by dividing MMRRs or SMR by 0.24 respectively. Results Number of myocarditis death which met the inclusion criteria were 32 cases. MMRR (95% confidence interval) was 4.03 (0.77 to 13.60) in 20s, 7.80 (2.85 to 18.56) in 30s, respectively. SMR of myocarditis was 1.69 (1.18 to 2.42) for overall vaccinated population, 1.35 (0.84 to 2.55) for those 60 years or older. Estimated adMMRRs and adSMR were about 4 times higher than the MMRRs and SMR. Pooled MOR for myocarditis were 148.49 (89.18 to 247.25). Conclusion SARS-CoV-2 vaccination was associated with higher risk of myocarditis death, not only in young adults but also in all age groups including the elderly. Considering healthy vaccinee effect, the risk may be 4 times or higher than the apparent risk of myocarditis death. Underreporting should also be considered. Based on this study, risk of myocarditis following SARS-CoV-2 vaccination may be more serious than that reported previously. SUMMARY BOXES ALREADY KNOWN ON THIS TOPIC There are many epidemiological studies showing increased myocarditis incidence after SARS-CoV-2 vaccination. There are also some case reports of fulminant myocarditis after receiving SARS-CoV-2 vaccine. However, no epidemiological studies focusing the association between vaccination and myocarditis death. WHAT THIS STUDY ADDS Myocarditis mortality rate ratios (MMRRs) and their 95% confidence intervals (95% CIs) after receiving SARS-CoV-2 vaccine compared with that in the reference population (previous 3 years) were higher not only in young adults (highest in the 30s with MMRR of 7.80) but also in the elderly. Standardised mortality ratio (SMR) for myocarditis was 1.35 (0.84 to 2.55) for those 60 years or older and 1.69 (1.18 to 2.42) in overall age. The risk of myocarditis mortality in the SARS-CoV-2 vaccinated population may be 4 times or higher than the apparent MMRRs considering healthy vaccinee effect. Unreported post-vaccination deaths should also be considered as suggested by the extremely high myocarditis mortality odds ratio (148.49; 89.18 to 247.25).