Myocarditis following COVID-19 vaccination: incidence, mechanisms, and clinical considerations

ABSTRACT

Introduction

Vaccines have demonstrated protection against the morbidity and mortality of COVID-19, but concerns regarding the rare side effect of acute myocarditis have stymied immunization efforts. This review aims to describe the incidence and theorized mechanisms of COVID vaccine-associated myocarditis and review relevant principles for management of vaccine-associated myocarditis

Areas covered

Epidemiologic studies of myocarditis after COVID vaccination are reviewed, which show an incidence of approximately 20–30 per million patients. The vast majority of these cases are seen with mRNA vaccines especially in male patients under 30 years of age. Mechanisms are largely theoretical, but molecular mimicry and dysregulated innate immune reactions have been proposed. While studies suggest that this subtype of myocarditis is mild and self-limited, long-term evidence is lacking. Principles of myocarditis treatment and surveillance are outlined as they apply to COVID vaccine-associated myocarditis.

Expert Opinion

COVID vaccine-associated myocarditis is rare but well described in certain at-risk groups. Better understanding of its pathogenesis is key to mitigating this complication and advancing vaccination efforts. Risk-benefit analyses demonstrate that individual- and population-level benefits of vaccination exceed the risks of this rare and mild form of myocarditis.

KEYWORDS:

• Myocarditis
• COVID-19
• vaccine
• incidence
• molecular mimicry
• innate immune system
• in vitro transcribed mRNA
• clinical

Article highlights

• The incidence of myocarditis in association with COVID-19 vaccines is estimated to be 20-30 per million patients

• Myocarditis incidence is higher with COVID-19 vaccines that use mRNA technology than those that use a traditional viral vector approach.

• Myocarditis is believed to affect males more than females due to differential effects of sex hormones on cytokine production.

• Even in at-risk populations, vaccine-associated myocarditis leads to far fewer hospitalizations than COVID-19 and causes much less morbidity and mortality.

• The risk of vaccine-associated myocarditis should only delay vaccination in patients with pre-existing unresolved myocarditis or pericarditis; all other patients are recommended to proceed with vaccination.

• Mechanisms for myocarditis are unclear but may include molecular mimicry as suggested by the high number of shared epitopes between SARS-CoV-2 spike protein and human self-antigens. Myocarditis may be triggered by cross-reactivity between COVID-19 vaccine mRNA components and RNA receptors of the innate immune system.

• General guidelines for managing myocarditis should be applied to vaccine-associated myocarditis with prompt immunosuppression for symptomatic patients, heart failure management if necessary, and standard precautions in the recovery phase

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers of this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This article was not funded.