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Myocarditis after BNT162b2 mRNA Vaccine against Covid-19 in Israel

Our take —

This observational study assessed myocarditis rates among Israelis 16 years and older between December 2020 to May 2021 by SARS-CoV-2 vaccination status in Israel by age and sex. Myocarditis cases were clinically adjudicated and incidences per 100,000 persons after first and second Pfizer-BioNTech mRNA vaccine doses were compared with unvaccinated individuals during the same time period and with myocarditis incidence observed before the COVID-19 pandemic. Vaccine-associated myocarditis cases were rare in all age and sex groups and over 90% of cases were mild and resolved quickly. Myocarditis was more likely after the second dose of the vaccine in all individuals, compared to both control groups. Adolescent males (aged 16-19 years) were at the highest risk of myocarditis after their second dose of the vaccine (15.07 cases per 100,000) compared to other age and sex groups. This study was not able to compare the incidence of vaccine-associated myocarditis with negative outcomes of SARS-CoV-2 infection (myocarditis, hospitalization, multisystem inflammatory syndrome, death, etc.).

Study design

Retrospective Cohort

Study population and setting

This observational study assessed myocarditis rates among individuals 16 years and older in Israel following the initiation of a national vaccination campaign (Pfizer-BioNTech vaccine) on December 20, 2020 through May 31, 2021. Myocarditis cases were initially identified via passive and active surveillance through the Israeli Ministry of Health. All cases were subject to adjudication from cardiologists and rheumatologists, and cases categorized as definitive or probable myocarditis were included in the analysis. Definitive and probable myocarditis case severity was described with available clinical data (length of stay, cardiac imaging, laboratory values, and time to symptom or imaging resolution). Myocarditis cases per 100,000 persons were compared by sex and age group among individuals after their first and second doses of the Pfizer-BioNTech SARS-CoV-2 vaccine (within 21 days of the first dose and 30 days of the second dose) with unvaccinated individuals during the same time period. Observed numbers of myocarditis cases were also compared with those seen among individuals 16 years and older in Israel from 2017-2019, before the COVID-19 pandemic. The study assessed myocarditis incidence per 100,000 persons, rate differences by group, and rate ratios between groups.

Summary of Main Findings

Approximately 9.2 million Israeli residents were included in the study period, about 5.1 million of whom received two doses of the Pfizer-BioNTech COVID-19 vaccine. They adjudicated 304 reported myocarditis cases and excluded 21 with a reasonable alternative diagnosis, 59 with insufficient data, and 4 suspected cases without sufficient information to classify them as probable. Of the remaining probable or confirmed cases (n=220), 107 occurred within 21 days of the first vaccine dose or 30 days of the second vaccine dose, 31 occurred in vaccinated individuals more than 21 days after the first dose or 30 days after the second dose (thereby classified as not vaccine-related), and 82 occurred in unvaccinated individuals (29 in individuals with diagnosed COVID-19). Of the 138 cases in vaccinated individuals, 129 (93.5%) were classified as mild with rapid resolution, 4 had severely-reduced ejection fraction (2.9%), and one died (0.7%).

Both male (RD 3.19 per 100,000 persons, 95% CI: 2.37, 4.02) and female (RD 0.39, 95% CI: 0.10, 0.68) participants were more likely to be diagnosed with myocarditis after their second dose compared to the first dose, with males aged 16-19 years experiencing the highest risk (15.07 cases per 100,000 persons). Overall, cases of myocarditis after vaccination were more common after the second dose than during the 2017-2019 reference period (standardized incidence ratio 5.34, 95% CI: 4.48, 6.40), with the highest incidence ratio in males aged 16-19 years (13.6, 95% CI: 9.3, 19.2). Overall, compared to the unvaccinated group, the second dose of the vaccine was associated with an increased rate of myocarditis (rate ratio 2.35, 95% CI: 1.1, 5.02), particularly among 16-19 year-old males (8.96, 95% CI: 4.50, 17.83).

Study Strengths

This study used population-level data with robust clinical adjudication to estimate the incidence of myocarditis after vaccination with the Pfizer-BioNTech vaccine by sex and age group. They also had access to baseline myocarditis incidence prior to the COVID-19 pandemic and incidence among unvaccinated individuals for comparison.

Limitations

While this study compared myocarditis incidence following vaccination to control individuals prior to the COVID-19 pandemic and unvaccinated individuals during the same time period, it did not include a comparison group of individuals diagnosed with SARS-CoV-2, which would have allowed readers to assess the risk of myocarditis following vaccination compared to the risk of myocarditis following COVID-19. It also did not have information on case severity among control participants, making it impossible to compare myocarditis severity following vaccination to other scenarios. Furthermore, this study did not provide information on myocarditis incidence in those younger than 16 years. Finally, given the small sample size, the analysis did not adjust for potential confounders beyond age and sex, such as underlying heart disease, immunological conditions, or medications that could cause myocarditis, all of which may be more common among vaccinated individuals.

Value added

This study provides evidence that adolescent males may be at increased risk of myocarditis following the second dose of the SARS-CoV-2 vaccine compared to baseline myocarditis incidence and incidence in similar unvaccinated individuals. However, it is unclear how clinically significant vaccine-associated myocarditis is compared to COVID-19 in this age group.

This review was posted on: 26 October 2021