Recent research has shown adolescents and young adults are at increased risk for myocarditis after receiving mRNA vaccinations (Pfizer-BioNTech and Moderna) for COVID-19.
A report from the BMJ demonstrated rates of myocarditis and myopericarditis in adolescents and adults post-vaccination, although case numbers were low overall. For adolescents aged 12-17 years, the absolute rate was 1 per 100,000 within 28 days of receiving the Pfizer vaccine; for individuals aged 12-39 years, it was 1.6 per 100,000. For those aged 12-39 years, the absolute rate was 5.7 per 100,000 after receiving the Moderna vaccine. No cases of myocarditis or myopericarditis were observed for adolescents aged 12-17 years who received Moderna.1
Research has also indicated that the condition affects young adults post-vaccination who are male.
Male Young Adults Who Develop Myocarditis After COVID-19 mRNA Vaccine
In a study published in October 2021 in JAMA Internal Medicine, researchers identified 15 cases of post-vaccination myocarditis (with 13 occurring after the second dose) among nearly 2.4 million adult members of a large US healthcare system. The observed incidence rate was 0.8 cases per 1 million first doses and 5.8 cases per 1 million second doses.2
All cases occurred in men with a median age of 25 years (IQR, 20-32), and 93% of patients reported chest pain within 5 days following vaccination. All patients experienced symptom resolution with conservative management, and none were readmitted following discharge.2
Myocarditis Post-Vaccination in Pediatric Populations
After vaccination became available for pediatric populations, multiple case studies and data from the Vaccine Adverse Events Reporting System (VAERS) have reflected a relative preponderance of cases in adolescent males, although cases remain rare overall.4-7 Among 530 cases of post-vaccination myocarditis reported to VAERS as of June 2021, approximately 65% of patients were aged 12-24 years.8
Similar to the outcomes observed in adults, adolescent patients have demonstrated a mild clinical course with high rates of complete recovery across studies.4-7
In a retrospective study published in December 2021 in Circulation, researchers examined data from 139 patients under the age of 21 years (90.6% male; median age, 15.8 years) who presented to 26 centers in the United States and Canada with suspected myocarditis in the 30 days following COVID-19 vaccination.9 Symptoms appeared within a median of 2 days, with most cases occurring after receipt of the second dose (91.4%). Chest pain represented the most common symptom, affecting 99.3% of patients.9
Among the 26 patients (18.7%) treated in the intensive care unit, the median stay was 2 days and no patients required extracorporeal membrane oxygenation (ECMO) or died. Of the 26 patients with left ventricular (LV) ejection fraction less than 55% on echocardiogram, 25 showed normalized function at follow-up and 1 did not present for follow-up.9
Given the higher prevalence rates noted in the adolescent population, we checked in with the following pediatric cardiology experts to learn more about these findings and relevant treatment recommendations: Elizabeth Profita, MD, clinical assistant professor of pediatric cardiology at Stanford Children’s Health in Palo Alto, California, and Gerard J. Boyle MD, FACC, medical director of pediatric heart failure and heart transplantation at Cleveland Clinic Children’s in Ohio.
What does the evidence suggest thus far about the risk of myocarditis associated with the COVID-19 vaccine?
Dr Profita: There have been increasing reports of myocarditis or pericarditis following COVID-19 mRNA vaccinations (Pfizer-BioNTech and Moderna), particularly in male adolescents. A recently published case report details 7 adolescent males who presented with chest pain within a few days of receiving the second dose of the Pfizer vaccine. All presented with chest pain, some had fever, all were negative for SARS-CoV2 by PCR, and none met criteria for multisystem inflammatory syndrome. All had cardiac MRIs consistent with myocarditis. They were treated with NSAIDs and all resolved symptoms quickly.7
This presentation has been consistent across centers, with the vast majority of cases presenting as chest pain in previously healthy male adolescents and young adults 2-5 days following the second vaccine dose, with significantly elevated troponin values. ECGs tend to be abnormal with ST changes, T wave inversions, and PR depressions; echos tend to show normal LV function or mild LV dysfunction and no effusion; and cardiac MRI is consistent with myocarditis. The majority of cases have self-resolved, with resolution of symptoms within a few days and normalization of cardiac MRI findings by about 3 months in many patients.
In the Pfizer BioNTech vaccine trial in children aged 5-11 years, there were no cases of myocarditis following vaccination, but the trial may have been too small to detect this rare complication.10 VAERS, through the Centers for Disease Control and Prevention and the Food and Drug Administration, continues to track data on vaccine-associated myocarditis.
What are the proposed mechanisms potentially driving this link?
Dr Boyle: COVID-19 vaccine-associated myocarditis remains a rare complication in the pediatric and young adult population. The proposed mechanism is the development of antibodies produced by patients against their own heart cells. These “self-directed” antibodies are the result of “molecular mimicry,” a phenomenon that occurs when the mRNA vaccines directed against the spike protein of the COVID -19 virus resemble proteins on the surface of the heart cells in some patients.3
What are the relevant recommendations for clinicians regarding detection and treatment of myocarditis in pediatric patients receiving the vaccine?
Dr Profita: Here at Stanford, we have developed recommendations regarding the evaluation and management of these patients. We would recommend evaluation of any patient with chest pain, shortness of breath, or palpitations within a week of receiving the COVID-19 mRNA vaccine, with troponin, BNP/NT-proBNP, CRP, and an ECG. If evaluation is reassuring, patients can be treated symptomatically with ibuprofen and followed on an outpatient basis.
If abnormal, we recommend further evaluation by pediatric cardiology including echo, and CMRI if troponin is elevated. Evaluation should also include consideration for other etiologies of symptoms or myocarditis. We would recommend inpatient admission for telemetry and serial troponin monitoring if troponin is elevated. Treatment consists of supportive care and symptom management with ibuprofen as needed. Patients with abnormal troponin, ECG, echo, or CMRI will need ongoing follow-up with pediatric cardiology.
Dr Boyle: The patients usually present to an ER or their pediatrician complaining of chest pain 2-3 days or more after their second dose of the vaccine. An ECG, echocardiogram, and blood tests can reliably diagnose myocarditis. For the most part, treatment is supportive care, though some require medications to help improve heart function or decrease inflammation based on the symptoms and degree of heart dysfunction. Almost all improve with or without specific treatment.4
What should be the focus of future research in this area?
Dr Profita: There is an ongoing need for tracking and data regarding myocarditis cases occurring after vaccination.
Dr Boyle: The mRNA vaccines have been part of research in the field of immunization for many years now and are not as new as most believe. Research specific to COVID-19 should be directed at defining the interval at which boosters need to be given, and to treatment of breakthrough infections to minimize the impact of infection. Additionally, this technology has the promise of potentially developing a “super-vaccine,” which may be directed at multiple potential viruses.
Given the risks associated with COVID-19 infection vs the rarity of, and recoverability from, post-vaccine myocarditis, it is strongly recommended that all eligible children and young adults be fully vaccinated.
- Husby A, Vinsløv Hansen J, Fosbøl E, et al. SARS-CoV-2 vaccination and myocarditis or myopericarditis: population based cohort study. BMJ. Published online December 16, 2021. doi:10.1136/bmj-2021-068665
- Simone A, Herald J, Chen A, e al. Acute myocarditis following COVID-19 mRNA vaccination in adults aged 18 years or older. JAMA Intern Med. Published online October 4, 2021. doi:10.1001/jamainternmed.2021.5511
- Bozkurt B, Kamat I, Hotez PJ. Myocarditis with COVID-19 mRNA vaccines. Circulation. 2021;144(6):471-484. doi:10.1161/CIRCULATIONAHA.121.056135
- Rosner CM, Genovese L, Tehrani BN, et al. Myocarditis temporally associated with COVID-19 vaccination. Circulation. 2021;144(6):502-505. doi:10.1161/CIRCULATIONAHA.121.055891
- Kaul R, Sreenivasan J, Goel A, et al. Myocarditis following COVID-19 vaccination. Int J Cardiol Heart Vasc. 2021;36:100872. doi:10.1016/j.ijcha.2021.100872
- Viskin D, Topilsky Y, Aviram G, et al. Myocarditis associated with COVID-19 vaccination: echocardiography, cardiac tomography, and magnetic resonance imaging findings. Circ Cardiovasc Imaging. 2021;14(9):e013236. doi:10.1161/CIRCIMAGING.121.013236
- Marshall M, Ferguson ID, Lewis P, et al. Symptomatic acute myocarditis in 7 adolescents after Pfizer-BioNTech COVID-19 vaccination. Pediatrics. 2021;148(3):e2021052478. doi:10.1542/peds.2021-052478
- Wallace M, Oliver S. COVID-19 mRNA vaccines in adolescents and young adults: benefit-risk discussion. Corporate Authors(s): United States. Advisory Committee on Immunization Practices (US ACIP) COVID-19 Vaccines Work Group. Conference Author(s): US ACIP Meeting, Atlanta, GA, May 12, 2021. Published June 23, 2021.
- Truong DT, Dionne A, Muniz JC, et al. Clinically suspected myocarditis temporally related to COVID-19 vaccination in adolescents and young adults. Circulation. Published online December 6, 2021. doi:10.1161/CIRCULATIONAHA.121.056583
- Walter EB, Talaat KR, Sabharwal C, et al. Evaluation of the BNT162b2 Covid-19 vaccine in children 5 to 11 years of age. N Engl J Med. Published online November 9, 2021. doi:10.1056/NEJMa2116298