As more autopsy research gets published in peer-reviewed journals, it is now acknowledged that the relationship between mRNA vaccine and myocarditis (inflamed heart muscles) is causal in nature; that is, mRNA vaccine is capable of causing myocarditis.
But this does not mean that the mRNA vaccine causes myocarditis in every case. Nationwide surveillance studies still find that the risk of mRNA vaccine-associated myocarditis is exceedingly low. And that mRNA vaccine-associated fatal myocarditis almost never happens, where surveillance studies could not find a significant difference.
That said, the pathology and pathogenesis of mRNA vaccine-associated myocarditis remain largely unknown. Several autopsy studies have found the presence of spike protein expression and infiltration of inflammatory immune cells in heart muscles in victims of mRNA vaccine-associated myocarditis. But these cases are usually from the older population, not young individuals.
To this end, medical doctors Gill et al. from Connecticut, the U.S. have autopsied two cases of fatal mRNA vaccine-associated myocarditis in teenage boys, discovering a different kind of myocarditis pathology that is not inflammatory in nature. They published their autopsy report in the Archives of Pathology and Laboratory Medicine, titled "Autopsy Histopathologic Cardiac Findings in 2 Adolescents Following the Second COVID-19 Vaccine Dose."
These two teenage boys (age unspecified; SARS-CoV-2-negative) died unexpectedly in their sleep within 4 days of getting Pfizer’s mRNA vaccine and were referred for judicial autopsy. One boy had a history of attention deficit hyperactivity syndrome, and the other boy had obesity.
The autopsy confirmed the cause of death to be fulminant (sudden and severe onset) myocarditis causally linked to the mRNA vaccine, with evidence of myocardial fibrosis (scarred heart muscles) and cardiac hypertrophy (thickened heart muscles). Notably, the lack of immune cell infiltrates in the autopsied tissues suggests a distinct form of myocarditis, perhaps Takotsubo, toxic, or stress cardiomyopathy.
"Their histopathology did not demonstrate a typical [inflammatory] myocarditis," Gill et al. wrote. "This injury pattern is instead similar to what is seen in the myocardium of patients who are clinically diagnosed with Takotsubo, toxic, or stress cardiomyopathy, which is a temporary myocardial injury that can develop in patients with extreme physical, chemical, or sometimes emotional stressors... It has also been called neurogenic myocardial injury and broken heart syndrome."
In such non-inflammatory myocarditis, neurochemical catecholamines (noradrenaline) seem to mediate myocardial (heart muscle) damage via mechanisms such as epicardial spasm, microvascular dysfunction, and hyperdynamic contractility in the heart.
At the biomolecular level, catecholamines damage myocytes (heart muscle cells) through cAMP–mediated calcium overload. Catecholamines can also induce free radicals, causing oxidative stress that can interfere with the sodium and calcium transporters of myocytes.
And several triggers can trigger a flood of catecholamines, including physical and emotional stressors. But how the mRNA vaccine triggers catecholamines remain unknown, and Gill et al. suspect that the immune responses against the mRNA vaccine may be one such physical trigger.
"Recognition that these instances are different from typical myocarditis and that cytokine storm has a known feedback loop with catecholamines may help guide screening, diagnosis, and therapy," Gill et al. concluded. Perhaps inhibitors of catecholamine receptors may work as a treatment for such instances of mRNA vaccine-associated, catecholamine-mediated myocarditis, but this requires further clinical research to investigate.
To put things into the proper context, such fatal cases of mRNA vaccine-associated myocarditis almost never happen, as mentioned earlier. A meta-analysis of 23 observation studies calculated that the fatality rate of mRNA vaccine-associated myocarditis is 0%. Therefore, myocarditis from the mRNA vaccine is much less fatal than myocarditis from virus infections, including SARS-CoV-2/Covid, with a 10-20% fatality rate. But given the global scale of vaccination by the billions, we are seeing ultrarare incidences at a more common occurrence.