Myocarditis associated with COVID-19 vaccination

Abstract

Following the start of the COVID-19 vaccination campaign, the adverse events of myocarditis and pericarditis were linked mainly to mRNA COVID-19 vaccines by the regulatory authorities worldwide. COVID-19 vaccines have been administered to several million people and the risk of myocarditis post COVID-19 vaccination has been characterised in great detail. At the present time the research data available are scarce and there is still no clear understanding of the biological mechanism/s responsible for this disease. This manuscript provides a concise overview of the epidemiology of myocarditis and the most prominent mechanistic insights in the pathophysiology of the disease. Most importantly it underscores the needed next steps in the research agenda required to characterize the pathophysiology of this disease post-COVID-19 vaccination. Finally, it shares our perspectives and considerations for public health.

Fig. 1. Summarizing overview of the potential mechanisms of myopericarditis following COVID-19 vaccination.

a The spike sequence introduced in the COVID-19 vaccines is the antigen recognized by the immune system, which activate specific immune responses, some of which could directly contribute to inflammation of the endothelium and cardiac tissue. b In the mRNA vaccines, the spike mRNA sequence is encapsulated in lipid nanoparticles (LNPs) for the delivery. The LNPs can elicit a variety of cytokines and chemokines, which can trigger a proinflammatory response with impact on the myo/pericardium. c Vaccine myocarditis is present mostly in young men, which suggests a role for sex hormones. While estradiol activates a T helper cell (Th) 2 response and anti-inflammatory cytokines, testosterone activates pro-inflammatory Th1 responses. d As myocarditis can be driven by autoimmune responses, molecular mimicry between spike protein and antigens associated with myocarditis in terms of protein sequence and structure could lead to myopericarditis by triggering cross-reactivity. e Genetic factors, such as specific HLA genes, may contribute to the risk to develop myocarditis upon mRNA vaccination as seen with viral infection associated myocarditis. The 3D structure image of estradiol, PubChem Identifier: CID 5757, was taken from URL: https://pubchem.ncbi.nlm.nih.gov/compound/Estradiol#section=3D-Conformer. The 3D structure image of testosterone, PubChem Identifier: CID 6013, was taken from https://pubchem.ncbi.nlm.nih.gov/compound/Testosterone#section=3D-Conformer.