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To the Editor: We previously reported that the incidence of myocarditis in Israel after receipt of the BNT162b2 messenger RNA vaccine (Pfizer–BioNTech) against coronavirus disease 2019 (Covid-19) was highest among males between the ages of 16 and 29 years (10.7 cases per 100,000 persons).1 BNT162b2 vaccination has since been approved for adolescents between the ages of 12 and 15 years, and initial evidence from this age group in Israel suggests a similar incidence and mild course of myocarditis, although follow-up was limited to 30 days.2 A study from Hong Kong showed an incidence of 28.7 cases per 100,000 persons, but cases were not adjudicated beyond the discharge diagnosis code of the International Classification of Diseases, Ninth Revision (ICD-9).3 Our aim was to provide further evidence regarding the incidence of myocarditis after vaccination among adolescents and data regarding follow-up of 6 months or more. We collected information about patients who were listed in the database of Clalit Health Services (the largest health care organization in Israel) from June 2 to November 30, 2021. We used ICD-9 codes to identify cases of myocarditis, which were adjudicated with the use of all available data in each patient’s electronic medical record. In-hospital and follow-up data were collected until February 26, 2022, as reported previously.1 Detailed methods and definitions are provided in the Supplementary Appendix, available with the full text of this letter at NEJM.org.

djudicated with the use of all available data in each patient’s electronic medical record. In-hospital and follow-up data were collected until February 26, 2022, as reported previously.1 Detailed methods and definitions are provided in the Supplementary Appendix, available with the full text of this letter at NEJM.org. Of 182,605 adolescents who had been vaccinated during this period, 20 potential cases of myocarditis were identified. A total of 9 cases were adjudicated as probable or definite myocarditis, according to the case definition of the Centers for Disease Control and Prevention. This finding translated to an incidence of 4.8 cases (95% confidence interval, 1.7 to 7.9) per 100,000 persons (Figure 1); 8 cases occurred after the second vaccine dose (Fig. S1 and Table S1 in the Supplementary Appendix). Incidence values that are stratified according to sex and age are provided in Table S2. All cases of myocarditis were classified as mild,4 and the condition of patients was hemodynamically stable at presentation. Abnormal electrocardiographic (ECG) results were reported in 67% of the patients, and cardiac and inflammatory markers were elevated in all the patients. The in-hospital course of the patients was uneventful, and the median duration of admission was 3 days (interquartile range, 2 to 4 days) (Table S3). Eight patients had a normal ejection fraction, and four had a pericardial effusion (Table S4).

ts, and cardiac and inflammatory markers were elevated in all the patients. The in-hospital course of the patients was uneventful, and the median duration of admission was 3 days (interquartile range, 2 to 4 days) (Table S3). Eight patients had a normal ejection fraction, and four had a pericardial effusion (Table S4). Echocardiographic findings were available for 8 of 9 patients after hospital discharge (median interval, 10 days). All echocardiograms showed a normal ejection fraction and resolution of pericardial effusion (in cases in which the latter had previously been identified). Five patients underwent cardiac magnetic resonance imaging (including three scans that were performed at a median of 104 days after discharge) with minimal evidence of myocardial scarring or fibrosis, with evidence of late gadolinium enhancement ranging from 0 to 2%. At a median follow-up of 206 days (interquartile range, 192 to 229 days) after hospital discharge, all the patients were alive and none had been readmitted to the hospital. Our study indicates that BNT162b2 vaccine–induced myocarditis in adolescents appears to be a rare adverse event that occurs predominantly in males after the second vaccine dose. The clinical course appears to be mild and benign over a follow-up period of 6 months, and cardiac imaging findings suggest a favorable long-term prognosis.

To the Editor: Using an active nationwide surveillance system administered by the Israeli Ministry of Health, we previously found a higher incidence of myocarditis among persons 16 years of age or older who had received the BNT162b2 vaccine (Pfizer–BioNTech) than among historical controls and unvaccinated persons; the incidence was highest among young male recipients.1 The Food and Drug Administration recently granted emergency use authorization for the two-dose regimen of the BNT162b2 vaccine in adolescents 12 to 15 years of age. Here, we report the incidence of hospitalization for myocarditis between June 2 and October 20, 2021, among adolescents in this age group within 21 days after receipt of the first vaccine dose and within 30 days after receipt of the second dose. Clinical data that involved International Classification of Diseases, 10th Revision, 422.0-9x and 429.0x codes were reviewed by a cardiologist and a rheumatologist, and the severity of disease was classified according to the Brighton Collaboration Case Definition for myocarditis (see the Supplementary Appendix, available with the full text of this letter at NEJM.org).2 These data were collected by the Israeli Ministry of Health. Pfizer–BioNTech had no role in the collection or analysis of the data or in the reporting of data in this letter.

righton Collaboration Case Definition for myocarditis (see the Supplementary Appendix, available with the full text of this letter at NEJM.org).2 These data were collected by the Israeli Ministry of Health. Pfizer–BioNTech had no role in the collection or analysis of the data or in the reporting of data in this letter. During the period under study, 404,407 adolescents (195,579 of whom were male) received the first dose of vaccine, 326,463 adolescents (157,153 of whom were male) received the second dose, and 18 cases of myocarditis leading to hospitalization were reported. Two cases of myocarditis were excluded from the study owing to reasonable alternative diagnoses. Of the remaining 16 cases, 1 occurred in an unvaccinated adolescent and 15 occurred in vaccinated adolescents — 1 case within 21 days after receipt of the first vaccine dose, 12 cases within 1 week after receipt of the second dose (Figure 1), and 2 later cases (1 each at 46 days and 70 days after receipt of the second dose); the 2 later cases were considered by the investigators as unlikely to be related to the vaccine.

scents — 1 case within 21 days after receipt of the first vaccine dose, 12 cases within 1 week after receipt of the second dose (Figure 1), and 2 later cases (1 each at 46 days and 70 days after receipt of the second dose); the 2 later cases were considered by the investigators as unlikely to be related to the vaccine. The demographic characteristics of the 13 adolescents with myocarditis occurring within 21 days after receipt of the first vaccine dose or within 30 days after receipt of the second dose are shown in Table S1 in the Supplementary Appendix. These 13 cases were classified as probable or definitive myocarditis according to the case definition. All the cases were clinically mild, involving a mean duration of hospitalization of 3.1 days (range, 1 to 6) and no readmissions during 30 days of follow-up. Symptoms at presentation, laboratory features, and echocardiographic findings are shown in Table S2. The risk estimates of myocarditis among male recipients in the 21 days after the first and second doses were 0.56 cases per 100,000 after the first dose and 8.09 cases per 100,000 after the second dose; the risk estimates among female recipients were 0 cases per 100,000 after the first dose and 0.69 cases per 100,000 after the second dose. The risk of myocarditis after receipt of the second vaccine dose among male adolescents 12 to 15 years of age was estimated to be 1 case per 12,361; the corresponding risk among female adolescents was estimated to be 1 case per 144,439.

per 100,000 after the first dose and 0.69 cases per 100,000 after the second dose. The risk of myocarditis after receipt of the second vaccine dose among male adolescents 12 to 15 years of age was estimated to be 1 case per 12,361; the corresponding risk among female adolescents was estimated to be 1 case per 144,439. The risk estimates per person in this study were lower than the previously reported risks among male recipients 16 to 24 years of age,1 but they were slightly higher than the Centers for Disease Control and Prevention estimate of approximately 1 case per 16,129 male recipients 12 to 17 years of age after receipt of the second dose.3 These differences may be explained by the active surveillance in our population. In a phase 3 trial of the BNT162b2 vaccine, the relatively small number of vaccinated adolescents 12 to 15 years of age (1131), of whom 567 were male, is a possible explanation for the absence of reported cases of myocarditis during the trial.4 Limitations of the current study are that myocarditis was not validated on myocardial biopsy, that misclassification and reporting bias may have taken place, and that we acquired only reports of cases of myocarditis that led to hospitalization. In conclusion, the incidence of myocarditis leading to hospitalization among adolescents who received the second dose of the BNT162b2 vaccine was low but was higher than among recipients of the first vaccine dose and proportionately numerically higher than in recent estimates of incidence among unvaccinated persons.