Between December 20, 2020 and May 24, 2021, a total of 2,558,421 Clalit Health Services members received at least one dose of the BNT162b2 Covid-19 mRNA vaccine; of these patients, 2,401,605 (94%) received two doses. Initially, 159 potential cases of myocarditis were identified using ICD-9 codes within 42 days of receiving the first dose of vaccine. After adjudication, 54 of these cases were considered to meet study criteria for a diagnosis of myocarditis. Of these cases, 41 were classified as mild in severity, 12 as intermediate and 1 as fulminant.
Of the 105 cases that did not meet the study criteria for a diagnosis of myocarditis, 78 were recoding of previous diagnoses of myocarditis with no new event, 16 did not have enough data available to meet the diagnostic criteria, and 7 preceded the first dose of vaccine; in 4 cases, a diagnosis of a condition other than myocarditis was determined to be more likely (Fig. S1). Community health records were available for all patients identified as potentially having myocarditis. Baseline hospital discharge summaries were available for 55 of 81 potential cases (68%) that did not register events and for 38 of 54 cases (70%) that met study criteria.
Characteristics of patients with myocarditis are provided in Table 1. The median age of the patients was 27 years (interquartile range [IQR], 21 to 35) and 94% were boys and men. Two patients had contracted Covid-19 before receiving the vaccine (respectively 125 days and 186 days earlier). Most patients (83%) had no coexisting medical condition; 13% were receiving treatment for chronic illnesses. One patient had mild left ventricular dysfunction prior to vaccination.
The cumulative incidence of myocarditis over a 42-day period after receiving the first dose of the 2019 BNT162b2 messenger RNA coronavirus disease vaccine (Covid-19) is shown. Myocarditis was diagnosed in 54 patients out of a global population of 2,558,421 vaccinated people enrolled in the largest healthcare organization in Israel. The vertical line at 21 days indicates the median day of administration of the second dose of vaccine. The shaded area shows the 95% confidence interval.
Of the patients with myocarditis, 37 (69%) were diagnosed after the second vaccine dose, with a median interval of 21 days (IQR, 21 to 22) between doses. A cumulative incidence curve of myocarditis after vaccination is shown in Figure 1. The distribution of days from vaccination to onset of myocarditis is shown in Figure S2. Both figures show events occurring throughout the post-vaccination period and indicate an increased incidence after the second dose.
Incidence of myocarditis
The estimated overall incidence of myocarditis within 42 days of receiving the first dose per 100,000 people vaccinated was 2.13 cases (95% confidence interval [CI], 1.56 to 2.70), which included an incidence of 4.12 (95% CI, 2.99 to 5.26) in men and 0.23 (95% CI, 0 to 0, 49) in women (Table 2). Among all patients aged 16 to 29, the incidence per 100,000 was 5.49 (95% CI, 3.59 to 7.39); among those who were 30 years of age or older, the incidence was 1.13 (95% CI, 0.66 to 1.60). The highest incidence (10.69 cases per 100,000 population; 95% CI, 6.93 to 14.46) was observed in male patients aged 16 to 29 years. In the general population, the incidence per 100,000 people by disease severity was 1.62 (95% CI, 1.12 to 2.11) for mild myocarditis, 0.47 (95% CI %, 0.21 to 0.74) for myocarditis intermediate and 0.04 (95% CI, 0 to 0.12) for fulminant myocarditis. Within each disease severity stratum, the incidence was higher in males than females and higher in patients aged 16 to 29 than in those aged 30 or older.
Clinical and laboratory results
The clinical and laboratory features of myocarditis are presented in Table 3 and Table S3. The telltale symptom was chest pain in 82% of cases. Vital signs on admission were generally normal; 1 patient presented with hemodynamic instability, and none required inotropic or vasopressor support or mechanical circulatory support during presentation. Electrocardiography (ECG) at presentation showed ST segment elevation in 20 of 38 patients (53%) for whom ECG data was available on admission; ECG results were normal in 8 of 38 patients (21%), while minor abnormalities (including T wave changes, atrial fibrillation, and unsupported ventricular tachycardia) were detected in the remainder. patients. The median peak troponin T level was 680 ng per liter (IQR, 275-2075) in 41 patients for which data were available, and the median creatine kinase level was 487 U per liter (IQR, 230-1193 ) in 28 patients for which data were available.
During hospitalization, cardiogenic shock leading to extracorporeal membrane oxygenation developed in 1 patient. None of the other patients required inotropic or vasopressor support or mechanical ventilation. However, 5% had unsupported ventricular tachycardia and 3% had atrial fibrillation. A myocardial biopsy sample obtained from 1 patient showed perivascular infiltration of lymphocytes and eosinophils. The median hospital stay was 3 days (IQR, 2 to 4). Overall, 65% of patients were discharged from the hospital without any ongoing medical treatment.
A patient with pre-existing heart disease died the day after discharge from an unspecified cause. A patient who had a history of pericarditis and had been admitted to hospital for myocarditis had three more admissions for recurrent pericarditis, with no further myocardial involvement after the initial episode. Additional clinical descriptions are provided in Table S4.
Echocardiography and other cardiac imaging
Echocardiographic results were available for 48 of 54 patients (89%) (Table S5). Among these patients, left ventricular function was normal on admission in 71% of patients. Of the 14 patients (29%) who had any degree of left ventricular dysfunction, 17% had mild dysfunction, 4% had mild to moderate dysfunction, 4% had moderate dysfunction, 2% had moderate to severe and 2% had severe malfunction malfunction. Among the 14 patients with some degree of left ventricular dysfunction at presentation, follow-up echocardiography during initial admission showed normal function in 4 patients and similar dysfunction in the remaining 10. The mean left ventricular function at outlet was 57.5 ± 6.1%, which was similar to the mean value at presentation. At a median follow-up of 25 days (IQR, 14 to 37) after discharge, echocardiographic follow-up was available for 5 of 10 patients whose last left ventricular workup before discharge showed some degree of dysfunction. Of these patients, all had normal left ventricular function; echocardiography follow-up results were not available for the remaining 5 patients.
Cardiac magnetic resonance imaging was performed in 15 patients (28%): in 5 patients on initial admission and in 10 patients at a median of 44 days (IQR, 21 to 70) after discharge. In all cases, left ventricular function was normal, with a mean ejection fraction of 61 ± 6%. Quantitative assessment data for late enhancement with gadolinium were available in 11 patients, with a median value of 5% (IQR, 1 to 15) (Table S6).