Abstract Background: Myocarditis induced by mRNA SARS-CoV-2 vaccines is a well-documented complication observed in young males, while increase of the incidence in sudden deaths among athletes have been reported and requires further investigation. Myocarditis is a major cause of sudden deaths in young male athletes. The severity and implications of these critical severe adverse effects request a thorough analysis aiming to elucidate the key mechanisms that trigger these events. Methods: To demonstrate, through a review in the literature, whether there is substantiation to hypothesize that catecholamines, in a sort of ‘hypercatecholinergic state’, are the key trigger of the mRNA SARS-CoV-2 vaccines-induced myocarditis and potential sudden deaths. Results: The rationale and data that support the hypothesis include: 1. mRNA COVID-19 vaccine-induced myocarditis particularly affects young males, and, although also may also be present in COVID-19 infection, complications such as heart arrhythmia are more commonly found after vaccines; 2. Independent autopsies of deaths due to mRNA COVID-19 vaccine in different geographical regions concluded that catecholamine-triggered myocarditis was the primary cause of all cases; 3. There is a dense presence of SARS-CoV-2 mRNA and progressive production of SARS-CoV-2 spike protein in chromaffin cells in the adrenal medulla, which are the responsible for the production of catecholamines; 4. There is an overexpression of DOPA-descarboxylase enzyme, that converts dopamine into noradrenaline, when in the presence of mRNA SARS-CoV-2, leading to enhanced activity of noradrenaline; 5. Catecholamine responses are physiologically higher in youngers and in males; 6. Catecholamine responses and resting catecholamine production are higher in male athletes than in non-athletes; 7. Catecholamine response to stress and sensitivity to catecholamines are enhanced in the presence of androgens; 8. Catecholamine responses, which are already high in young male athletes, are overexpressed in vaccinated athletes, when compared to pre-vaccination levels and non-vaccinated athletes. Conclusion: Epidemiological, autopsies, molecular and physiological findings unanimously and strongly suggest that a ‘hypercatecholinergic’ state is the critical predictor that triggers mRNA COVID-19 vaccine-induced myocarditis and potential increase in sudden deaths among elite athletes.
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