Similarities and Differences Between Myocarditis Following COVID-19 Mrna Vaccine and Multiple Inflammatory Syndrome with Cardiac Involvement in Children

Abstract Text: SARS-CoV-2 vaccines have been the most efficient measure in COVID-19 pandemic management, with a reduction in morbidity and mortality. Despite the multiple benefits, myopericarditis after COVID-19 vaccination have been reported. Considering male predominance and inflammation characteristic of myocarditis (MYO), we investigated androgens levels along with clinical, routine laboratory and proteomic analysis in MYO (n=15,mean age 15.72yrs), in comparison with age and gender-matched Multisystem inflammatory syndrome in children (MIS-C) (n=14, mean age 13.07yrs), SARS-CoV-2-infected children (n=21, mean age 15.16yrs) and healthy controls (n=31) (mean age 15.12 years). Correction for multiple comparisons was performed by False Discovery Rate method, considering statistically significant for those with an adjusted p-value < 0.05. Our analysis showed higher level of testosterone, DHEAS, DHEA, androstenedione and cortisone in MYO which persisted months after the acute event, suggesting a primary higher level and a potential role for these hormones in the pathogenesis. Proteomic analysis showed higher levels of proteins involved in generalized inflammation in MIS-C and SARS-CoV-2 compared to MYO, where the heart-related inflammation proteins appeared higher. Indeed, proteins related to systemic inflammation (IFN-gamma, CXCL9, CXCL10) were found higher in MIS-C compared to MYO, whereas a higher level in proteins related to cardiomyocyte apoptosis and myocardial injury (SIRT2, STAMBP, AXIN1) was found in MYO. In conclusion, we showed that a peculiar androgen profile in adolescents may favor myocarditis pathogenesis along with a specific heart-restricted inflammation following mRNA vaccination. Additional studies are needed to further confirm this hypothesis. Despite these findings, the benefits of the COVID19 immunization still outrage the risks.