Methods

In this follow-up follow-up study, we investigated US subjects aged 12–29 years with myocarditis after vaccination with COVID-19 mRNA who had been reported to the Vaccine Adverse Event Reporting System between January 12 and November 5, 2021 Granted a two-component study, one component in patients (or parents or guardians) and one component in health care providers, to assess patient outcomes at least 90 days after the onset of myocarditis. Data collected were recovery status, cardiac monitoring and functional status, and EuroQol health-related quality of life measures (dichotomized as no problem or no problem) and a weighted quality of life measure, ranging from 0 to 1 ( very healthy). EuroQol results were compared with published results in US populations (aged 18–24 years) before and early in the COVID-19 pandemic.

Foundings

Between August 24, 2021, and January 12, 2022, we collected data for 519 (62%) of 836 eligible patients who were at least 90 days after the onset of myocarditis: 126 patients via patient survey only, 162 patients via health care provider survey only, and 231 patients through both surveys. Median patient age was 17 years (IQR 15–22). 457 (88%) patients were male and 61 (12%) female. 320 (81%) of 393 patients with health care provider assessment were considered recovered from myocarditis by the health care provider, although at the last health care provider follow-up, 104 (26%) of 393 patients were prescribed daily myocarditis-related medication. Of 249 subjects who completed the quality of life portion of the patient survey, four (2%) reported problems with self-care, 13 (5%) with mobility, 49 (20%) with performing usual activities, 74 (30%) with pain and 114 (46%) with depression. Weighted mean quality of life measure (0.91 [SD 0·13]) was similar to a pre-pandemic US population value (0.92 [0·13]) and significantly higher than the early pandemic US population value (0.75 [0·28]; p<0·0001). Most patients had improvements in cardiac index and test data at follow-up, including normal or troponin concentrations back to baseline (181 [91%] from 200 patients with available data), echocardiograms (262 [94%] from 279 patients), electrocardiograms (240 [77%] of 311 patients), exercise stress test (94 [90%] of 104 patients) and ambulatory rhythm monitoring (86 [90%] from 96 patients). An abnormality was noted among 81 (54%) of 151 patients with cardiac MRI follow-up. However, evidence of myocarditis is indicated by the presence of both late gadolinium enhancement and edema on cardiac MRI (20 [13%] from 151 patients). At follow-up, most patients were cleared for any physical activity (268 [68%] from 393 patients).

Interpretation

After at least 90 days from the onset of post-mRNA vaccination for COVID-19 myocarditis, most subjects in our cohort were considered recovered by healthcare providers, and quality-of-life measures were comparable to those in pre-pandemic and early-pandemic populations similar age. These findings may not be generalizable given the small sample size, and further follow-up is needed for the subgroup of patients with atypical test results or who are not considered to have recovered.

Financing

US Centers for Disease Control and Prevention.

Introduction

Evidence from the US and multiple international vaccine safety surveillance systems supports a small but increased risk of myocarditis after vaccination with COVID-19 mRNA. mRNA vaccines for COVID-19. In 2021, data from the Vaccine Adverse Event Reporting System (VAERS) showed that in US persons aged 12 years and older, approximately 4.8 cases of myocarditis were reported per million doses of mRNA COVID-19 vaccines administered, with the highest reporting rates in ages 12–29 years.2

Gargano JW Wallace M Hadler SC et al.

Use of COVID-19 vaccine mRNA after reports of myocarditis among vaccine recipients: update from the Advisory Committee on Immunization Practices—United States, June 2021. Despite a higher-than-expected incidence of myocarditis after vaccination against COVID-19, the benefits of COVID-19 mRNA vaccines have been shown to outweigh the risk of myocarditis.2

Gargano JW Wallace M Hadler SC et al.

Use of COVID-19 vaccine mRNA after reports of myocarditis among vaccine recipients: update from the Advisory Committee on Immunization Practices—United States, June 2021.3

Block JP Boehmer TK Forrest CB et al.

Cardiac complications after SARS-CoV-2 infection and vaccination with COVID-19 mRNA—PCORnet, United States, January, 2021–January, 2022.Research in context Evidence prior to this study In December 2020, the US Food and Drug Administration (FDA) issued emergency use authorizations (EUAs) for the Pfizer-BioNTech COVID-19 vaccine (BNT162b2) and the Moderna COVID-19 vaccine (mRNA-1273). In May 2021, the FDA expanded the EUA for the BNT162b2 vaccine to include adolescents aged 12–15 years. By July 2022, more than 200 million people in the US had received two doses of mRNA vaccine for COVID-19, and more than 1500 cases of myocarditis with onset after vaccination with mRNA COVID-19 were reported to the Vaccine Adverse Event Reporting System (VAERS). . We searched PubMed for articles published up to April 30, 2022, using the keywords “mRNA vaccine” and “myocarditis,” with no language restrictions. Systematic reviews published in 2022 included more than 5299 people with myocarditis after mRNA vaccination and suggested that the risk was higher in adolescents and young men after a second dose of vaccine. Findings from these systematic reviews suggest that most cases of myocarditis following mRNA vaccination for COVID-19 have resolution of symptoms by or soon after discharge from a short hospital stay. However, data on medium-term outcomes for adolescents and young adults diagnosed with myocarditis after COVID-19 mRNA vaccination are scarce. Added value of this study To our knowledge, this is the largest assessment of outcomes among patients diagnosed with myocarditis after COVID-19 mRNA vaccination with a follow-up of at least 90 days from onset. We collected data from both patients (or their parents or guardians) and healthcare providers and assessed a comprehensive array of outcomes, including cardiac monitoring biomarkers, cardiac magnetic resonance imaging, echocardiograms, troponin levels, and electrocardiograms. We found that 320 (81%) of 393 patients with health care provider assessment were considered recovered from myocarditis, and quality-of-life measures were similar to pre-pandemic or early-pandemic measures. No single diagnostic test or clinical characteristic appeared to be associated with recovery status. Consequences of all available evidence Myocarditis after vaccination with mRNA for COVID-19 is rare but potentially serious. To better understand potential long-term complications of myocarditis, continued follow-up is important, particularly for patients who have not recovered at least 90 days from the onset of symptoms. Vaccination remains the most effective way to prevent morbidity and mortality from COVID-19. Cardiac evaluation of patients diagnosed with myocarditis after vaccination with mRNA for COVID-19 often shows elevated cardiac biomarkers (eg, troponin concentrations) and atypical cardiac imaging (eg, echocardiogram), which are similar findings to appearing for viral or acute myocarditis., 5

Oster ME Shay DK Your youngest. et al.

Cases of myocarditis reported after mRNA-based COVID-19 vaccination in the US from December 2020 to August 2021. Viral myocarditis not associated with mRNA vaccination for COVID-19 can lead to heart failure, heart transplantation, or death.6

Ghelani SJ Spaeder MC Pastor W Spurney CF Klugman D

Demographics, trends, and outcomes in pediatric acute myocarditis in the United States, 2006 to 2011. In contrast, case reports suggest that clinical outcomes following a diagnosis of myocarditis following mRNA vaccination for COVID-19 are more favorable than those associated with viral myocarditis, with resolution of symptoms often described at or soon after discharge from hospital for myocarditis after mRNA COVID-19 -19 vaccination.5

Oster ME Shay DK Your youngest. et al.

Cases of myocarditis reported after mRNA-based COVID-19 vaccination in the US from December 2020 to August 2021.7

Sinagra C Anzini M Pereira NL et al.

Myocarditis in clinical practice.8

Witberg G Varda N Hoss S et al.

Myocarditis after vaccination against COVID-19 in a large healthcare organization.9

Truong DT Dionne A. Muniz JC et al.

Clinically suspected myocarditis temporally associated with vaccination against COVID-19 in adolescents and young adults: suspected myocarditis after vaccination against COVID-19. However, data on follow-up outcomes for adolescents and young adults diagnosed with myocarditis after COVID-19 mRNA vaccination are scarce.10

Amir G Rothstein A reason and et al.

CMR imaging 6 months after BNT162b2 mRNA COVID-19 vaccine-associated myocarditis.11

Fronza M Thaventiranathan P Karur GR et al.

Cardiac MRI and clinical follow-up in myocarditis associated with the COVID-19 vaccine.12

Jain SS Steele JM Fonseca B et al.

Myocarditis associated with COVID-19 vaccination in adolescents. To conduct surveillance, the US Centers for Disease Control and Prevention (CDC) developed an operational myocarditis case definition with a subspecialty panel that has been used in several studies.2

Gargano JW Wallace M Hadler SC et al.

Use of COVID-19 vaccine mRNA after reports of myocarditis among vaccine recipients: update from the Advisory Committee on Immunization Practices—United States, June 2021.5

Oster ME Shay DK…