Acute Myocarditis Following COVID-19 mRNA Vaccination in Adults Aged 18 Years or Older

Abstract

This cohort study examines the incidence and clinical outcomes of acute myocarditis among adults following mRNA vaccination in an integrated health care system in the US.

Vaccination is an essential component of the public health strategy to end the COVID-19 pandemic.^1,2,3 Recently, there have been reports of acute myocarditis following COVID-19 mRNA vaccine administration.^4,5,6 We evaluated acute myocarditis incidence and clinical outcomes among adults following mRNA vaccination in an integrated health care system in the US.

Methods

We included Kaiser Permanente Southern California (KPSC) members aged 18 years or older who received at least 1 dose of the BNT162b2 (Pfizer) or mRNA-1273 (Moderna) mRNA vaccine between December 14, 2020, and July 20, 2021. Potential cases of postvaccine myocarditis were identified based on reports from clinicians to the KPSC Regional Immunization Practice Committee and by identifying hospitalization within 10 days of vaccine administration with a discharge diagnosis of myocarditis. All cases were independently adjudicated by at least 2 cardiologists. We calculated incidence rates and 95% confidence intervals (CIs) of myocarditis using vaccine administration as the denominator and compared it with the incidence of myocarditis in unexposed individuals between December 14, 2020, and July 20, 2021; and with vaccinated individuals during a 10-day period 1 year prior to vaccination. Incidence rate ratios (IRRs) and 95% CIs were calculated using STATA statistical software (version 14, Stata Corp). We described the characteristics and outcomes of acute myocarditis cases. A 2-sided P < .05 was used to define statistical significance. This study was approved by the institutional review board of KPSC with a waiver of informed consent because of the observational nature of the study in the course of standard care.

Results

Of 2 392 924 KPSC members who received at least 1 dose of COVID-19 mRNA vaccines, 50.2% received mRNA-1273 and 50.0% BNT162b2. In this cohort, 54.0% were women, 31.2% White, 6.7% Black, 37.8% Hispanic, and 14.3% were Asian individuals. Median age was 49 years (IQR, 34-64 years), 35.7% were younger than 40 years, and 93.5% completed 2 doses of vaccines. In the unexposed group of 1 577 741 individuals, median (IQR) age was 39 (28-53) years, 53.7% were younger than 40 years, 49.1% women, 29.7% White, 8.8% Black, 39.2% Hispanic, and 6.6% were Asian individuals.

There were 15 cases of confirmed myocarditis in the vaccinated group (2 after the first dose and 13 after the second), for an observed incidence of 0.8 cases per 1 million first doses and 5.8 cases per 1 million second doses over a 10-day observation window (Table 1). All were men, with a median (IQR) age of 25 (20-32) years. Among unexposed individuals, there were 75 cases of myocarditis during the study period, with 39 (52%) men and median (IQR) age of 52 (32-59) years. The IRR for myocarditis was 0.38 (95% CI, 0.05-1.40) for the first dose and 2.7 (95% CI, 1.4-4.8) for the second dose. Sensitivity analyses using vaccinated individuals as their own controls showed similar findings (Table 1).

Table 1. Incidence Rates and Rate Ratios of Myocarditis in Vaccinated Individuals Compared With Control Groups.

Variable	Myocarditis cases, No.	No. of at-risk individuals	Follow-up time, person-days	Incidence over a 10-d observation period per 1 million individuals (95% CI)	Incidence rate ratio (95% CI)	P value
Compared with individuals who did not receive the COVID-19 mRNA vaccine
Unexposeda	75b	1 577 741	343 947 538	2.2 (1.7-2.7)
0-10 d After dose 1	2	2 392 924	23 929 240	0.8 (0.2-3.3)	0.38 (0.05-1.40)	.15
0-10 d After dose 2	13	2 236 851	22 368 510	5.8 (3.4-10)	2.7 (1.4-4.8)	.004
Compared to the same cohort during a 10-d period 1 y prior to vaccinationc
During a 10-d observation period 1 y prior to dose 1	2	2 392 924	23 929 240	0.8 (0.2-3.3)
0-10 d After dose 1	2	2 392 924	23 929 240	0.8 (0.2-3.3)	1.0 (0.1-13.8)	>.99
During a 10-d observation period 1 y prior to dose 2	4	2 236 851	22 368 510	1.8 (0.7-4.8)
0-10 d After dose 2	13	2 236 851	22 368 510	5.8 (3.4-10)	3.3 (1.0-13.7)	.03

Abbreviation: KPSC, Kaiser Permanente Southern California.

^a Members of the KPSC integrated health system who did not receive the COVID-19 mRNA vaccine between December 14, 2020, and July 20, 2021.

^b Number of myocarditis cases between December 14, 2020, and July 20, 2021; 24 cases were in individuals aged 18 to 40 years.

^c Using vaccinated individuals as their own controls. Myocarditis cases were identified during a 10-day period. For the vaccinated group, the 10-day postvaccination period was measured from the day of vaccination until day 10 after vaccination. For control, a 10-day period began 365 days prior to their vaccination date and ended 355 days prior to their vaccination date.

Of the patients with myocarditis postvaccination, none had prior cardiac disease (Table 2). Eight patients received BNT162b2 and 7 received mRNA-1273. All were hospitalized and tested negative for SARS-CoV-2 by polymerase chain reaction on admission. Fourteen (93%) reported chest pain between 1 to 5 days after vaccination. Symptoms resolved with conservative management in all cases; no patients required intensive care unit admission or readmission after discharge.

Table 2. Case Description and Clinical Course^a.

Patient No.	Demographicsb	Days to chest pain onset	ECG	Troponin I peak, ng/mL	Evaluation of CAD	LVEF on echo, %	LOS, d
1	18-25 y, White man	7	Diffuse ST elevation	8.10	No CT evidence of CAD	55-60	3
2	18-25 y, White man	5	Inferolateral T wave inversion	8.87c	No CT evidence of CAD	55-60	2
3	18-25 y, White man	5	Sinus tachycardia, no ischemic changes	1.59c	No CT evidence of CAD	60-65	3
4	26-40 y, White man	3	No ischemic changes	2.50	Normal coronaries on cardiac catheterization	60-65	3
5	26-40 y, Hispanic man	3	Diffuse ST elevation	1.53c	Normal coronaries on cardiac catheterization	55-60	1
6	26-40 y, White man	3	Diffuse ST elevation	17.12c	Normal coronaries on cardiac catheterization	45, Global hypokinesis	3
7	18-25 y, White man	4	Diffuse ST elevation	5.00	No cardiac catheterization or CT performed	60-65	2
8	18-25 y, Hispanic man	2	Diffuse ST elevation	11.79	No CT evidence of CAD, MRI with myopericarditis	50-55	3
9	18-25 y, White man	3	No ischemic changes	7.37	No CT evidence of CAD	55-50	5
10	26-40 y, Hispanic man	1	No ischemic changes	2.98	Normal coronaries on cardiac catheterization	60-65	3
11	26-40 y, man, unknown ethnicity	3	Diffuse ST elevation	32.30	No CT evidence of CAD	55-60	3
12	26-40 y, White man	1	Diffuse ST elevation	6.28	No cardiac catheterization or CT performed	55-60	1
13	18-25 y, Hispanic man	3	Diffuse ST elevation	16.9	No cardiac catheterization or CT performed	30-35, Global hypokinesisd	3
14	18-25 y, White man	1	Diffuse ST elevation	15.9c	No cardiac catheterization or CT performed	50-55	3
15	26-40 y, Asian man	2	Diffuse ST elevation	0.49c	No CT evidence of CAD	50-55	3

Abbreviations: CAD, coronary artery disease; CT, computed tomography; ECG, electrocardiogram; Echo, echocardiogram; LOS, length of stay; LVEF, left ventricular ejection fraction; MRI, magnetic resonance imaging.

^a To confirm myocarditis, the following criteria were used (1) symptoms consistent with myocarditis, (2) elevated troponin I level, (3) no evidence of obstructive coronary artery disease, and (4) no other identifiable cause.

^b Self-reported race and ethnicity from the electronic health record. To protect patient privacy, patient age was designated as either 18 to 25 or 26 to 40 years.

^c High-sensitivity troponin I values were converted from pg/mL to ng/mL (99th upper reference limit: 0.02 ng/mL).

^d LVEF recovered on a follow-up echocardiogram.

Discussion

In this population-based cohort study of 2 392 924 individuals who received at least 1 dose of COVID-19 mRNA vaccines, acute myocarditis was rare, at an incidence of 5.8 cases per 1 million individuals after the second dose (1 case per 172 414 fully vaccinated individuals). The signal of increased myocarditis in young men warrants further investigation.

This vaccinated cohort is unique in its racial and ethnic diversity and in receiving care at community hospitals with treatment reflective of real-world practice. Limitations of this study include the observational design; short follow-up time; absence of myocardial biopsy for definitive diagnosis; lack of uniform testing of all cases; possible more extensive workup of chest pain in vaccinated individuals during the immediate postvaccination period; and possible underdiagnosis of subclinical cases. No relationship between COVID-19 mRNA vaccination and postvaccination myocarditis can be established given the observational nature of this study.