Abstract
BACKGROUND: COVID-19 mRNA vaccines have proven to be highly safe and effective. Myocarditis is an adverse event associated with mRNA vaccination, especially in young male subjects. These events are rare and, in the majority of cases, resolve quickly. As myocarditis can be driven by autoimmune responses, we wanted to determine if the SARS-CoV-2 spike protein antigen encoded in the mRNA COVID vaccines had potential cross-reactivity with auto-antigens previously associated with myocarditis. METHODS: We performed a sequence identity comparison between SARS-CoV-2 spike protein-derived peptides and myocarditis-associated antigens. We also performed a structural analysis of these antigens and the SARS-CoV-2 spike protein to identify potential discontinuous 3-D epitope similarities. FINDINGS: We found no significant enrichment in the frequency of spike-derived peptides similar to myocarditis-associated antigens as compared to several controls. INTERPRETATION: Our results do not support the notion that increased occurrence of myocarditis after SARS-CoV-2-spike vaccination is mediated by a cross-reactive adaptive immune response.