Vaccination against SARS CoV-2 has made a tremendous difference and impact on the course of the SARS CoV-2 pandemic. This is indisputable. Vaccination against SARS CoV-2 has saved lives. That is indisputable.

That said, it is clear that vaccination against SARS CoV-2 also comes with risks. It is not completely benign. That is also indisputable. Specifically, vaccination against SARS CoV-2 has been associated with myocarditis/pericarditis, especially in adolescent and young adult males.

The mechanism of this very rare, albeit very real, complication (estimated to be between 0 to 35.9 cases per 100,000 across age groups and mRNA vaccine cohorts) has been thought to be either an allergic reaction, an autoimmune reaction from the vaccine, or a cross-reaction from the antibodies generated by the vaccine itself.

Researchers from Yale University have elucidated the actual cause of myocarditis. They studied 23 patients with vaccine-associated myocarditis and/or pericarditis. They did extensive and exquisite studies on these patients, and here their conclusions:

our results demonstrate up-regulation in inflammatory cytokines and corresponding lymphocytes with tissue-damaging capabilities, suggesting a cytokine-dependent pathology, which may further be accompanied by myeloid cell–associated cardiac fibrosis. These findings likely rule out some previously proposed mechanisms of mRNA vaccine–-associated myopericarditis and point to new ones with relevance to vaccine development and clinical care.

Thus, it is the actual immune system itself – revved up by the vaccine – that directly damage the heart muscle itself. Now, this raises a number of questions: why more often in young males? Why the heart and not other organs? If there could be scarring in the heart, then what are the long-term effects? What does this mean for future mRNA vaccines? Hopefully, these and even more questions will be answered with further research.

Yes, the cohort is quite small, and it may be difficult to extrapolate these findings to all patients with vaccine-induced myocarditis. Nonetheless, the findings are an important contributor to the literature. It emphasizes the great importance to follow these patients long-term to make sure they don’t have any long-term complications. In addition, it is quite important to highlight what the researchers themselves pointed out about their findings:

It is also critical to contextualize the rare risk of adverse events and potential clinical sequelae after SARS-CoV-2 vaccination in comparison with the greater risks of sequelae (including myocarditis), hospitalization, and/or death resulting from infection with SARS-CoV-2.

Indeed, according to the CDC, the risk of cardiac complications of the infection itself far far outweighs the risk of myocarditis from the vaccine:

Hopefully, further research will add to this study’s important body of knowledge and help us develop even safer vaccines for the next pandemic.

Study Reference: Anis Barmada, et al. Cytokinopathy with aberrant cytotoxic lymphocytes and profibrotic myeloid response in SARS-CoV-2 mRNA vaccine–associated myocarditis. Sci.Immunol.8,eadh3455(2023). DOI:10.1126/sciimmunol.adh3455