The Epidemiology of COVID-19 Vaccine-Induced Myocarditis

Abstract

Background: In December 2019, the emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) led to the COVID-19 pandemic, with millions of deaths worldwide. Vaccine breakthroughs in late 2020 resulted in the authorization of COVID-19 vaccines. While these vaccines have demonstrated efficacy, evidence from vaccine safety monitoring systems around the globe supported a causal association between COVID-19 vaccines, in particular those using mRNA technology, i.e., Moderna's mRNA-1273 and Pfizer-BioNTech's BNT162b2, and myocarditis.

Objective: This paper aims to investigate the epidemiology of mRNA COVID-19 vaccine-induced myocarditis, including age, ethnicity, and gender associations with these vaccines. It also discusses the immunopathophysiological mechanisms of mRNA COVID-19 vaccine-associated myocarditis and outlines principles of diagnosis, clinical presentation, and management.

Methods: A literature review was conducted using PubMed, Embase, and Queen Mary University of London Library Services databases. Search terms included "myocarditis," "coronavirus disease 2019," "SARS-CoV-2," "mRNA Covid-19 vaccines," "Covid vaccine-associated myocarditis," "epidemiology," "potential mechanisms," "myocarditis diagnosis," and "myocarditis management."

Results: While the definite mechanism of mRNA COVID-19 vaccine-associated myocarditis remains ambiguous, potential mechanisms include molecular mimicry of spike proteins and activation of the adaptive immune response with dysregulated cytokine expression. Male predominance in COVID-19 vaccine-induced myocarditis may be attributed to sex hormones, variations in inflammatory reactions, coagulation states based on gender, and female-specific protective factors. Moreover, an analysis of diagnostic and management strategies reveals a lack of consensus on acute patient presentation management.

Conclusion: In contrast to viral infections that stand as the predominant etiological factor for myocarditis with more severe consequences, the mRNA COVID-19 vaccination elicits a mild and self-limiting manifestation of the condition. There is currently insufficient evidence to confirm the definite underlying mechanism of COVID-19 vaccine-associated myocarditis. Further research is needed to develop preventive and therapeutic solutions in this context.

Figure 1

Summary of the different forms of myocarditis classified as acute, subacute, chronic, and fulminant.

Figure 2

Overview of the diagnostic investigations of myocarditis and respective findings. ESR: erythrocyte sedimentation rate; CRP: C-reactive protein.

Figure 3

Visual representation of the mechanism of action of the mRNA vaccine: the lipid nanoparticle and mRNA vaccine complex enter the muscle cell or APC by endocytosis. Translocation and translation to spike proteins take place in the ribosomes. Secretion of the spike protein into the extracellular environment, internalization into APCs via endocytosis, and incorporation as part of MHC class II take place. Antibody and cell-mediated immunity against SARS-CoV-2 take place.

Figure 4

Illustration of the CDC definition of myocarditis. ECG: electrocardiogram; TTE: transthoracic echocardiogram; MRI: magnetic resonance imaging.

Figure 5

Illustration of the clinical characteristics of COVID-19 vaccine-induced myocarditis. ECG: electrocardiogram; TTE: transthoracic echocardiogram.

Figure 6

Illustration of the original and updated Lake Louise Criteria that can be used to establish the diagnosis of clinically suspected myocarditis.

Figure 7

Illustration of the potential workflow of CMR use in patients with suspected COVID-19 vaccine-induced myocarditis. ECG: electrocardiogram; TTE: transthoracic echocardiogram.