Transient Blood Release of Synthetic SARS-Cov-2 Spike Protein after mRNA-Based COVID-19 Vaccination Possibly Contributes to ACE2 Dysfunction Leading to Rare Cases of Myocarditis

Author(s): Christian A Devaux, Laurence Camoin-Jau

Myocarditis has been recognized as a possible rare complication of COVID-19 mRNA vaccination. It concerns between 0.3 and five vaccinated people per 100,000 in the general population, with increased incidence in adolescent and young adult men. Most often, cases of myocarditis have been reported in the days following the second dose of vaccine mainly in younger male patients. This complication of vaccination usually resolves within days or weeks. However, the pathophysiological events responsible for the increase in frequency of myocarditis after COVID-19 vaccination remain unclear. Recent reports have highlighted that free spike proteins circulating in patients' blood at high levels appear to play a major role in myocarditis. Here, we review the most recent data that partly lift the veil on the molecular mechanisms of the induction of myocarditis following mRNA-based COVID-19 vaccination. We hypothesize that a mechanism of molecular mimicry of the viral spike triggers transient dysregulation of angiotensin-converting enzyme 2, leading to increased soluble angiotensin II binding to the transmembrane receptor angiotensin II type I receptor, similar to what is observed during SARS-CoV-2 infection. We suggest to standardize the management of suspected cases of mRNA-based COVID-19 vaccine-induced myocarditis, including the monitoring of angiotensin II and spike antigenemia.