14. Myocarditis
There has been considerable media attention devoted to the fact that COVID-19 vaccines cause myocarditis and pericarditis, with an increased risk in particular for men below the age of 30 [197,200]. Myocarditis is associated with platelet activation, so this could be one factor at play in the response to the vaccines [201]. However, another factor could be related to exosomes released by macrophages infected with the mRNA vaccines, and the specific microRNAs found in those exosomes.
A study involving patients suffering from severe COVID-19 disease looked specifically at the expression of circulating microRNAs compared to patients suffering from influenza and to healthy controls. One microRNA that was consistently upregulated in association with COVID-19 was miR-155, and the authors suggested that it might be a predictor of chronic myocardial damage and inflammation. By contrast, influenza infection was not associated with increased miR-155 expression. They concluded: “Our study identified significantly altered levels of cardiac-associated miRs in COVID-19 patients indicating a strong association of COVID-19 with cardiovascular ailments and respective biomarkers” [202].
A study comparing 300 patients with cardiovascular disease to healthy controls showed a statistically significant increase in circulating levels of miR-155 in the patients compared to controls. Furthermore, those with more highly constricted arteries (according to a Gensini score) had higher levels than those with lesser disease [203].
Importantly, exosomes play a role in inflammation in association with heart disease. During myocardial infarction, miR-155 is sharply upregulated in macrophages in the heart muscle and released into the extracellular milieu within exosomes. These exosomes are delivered to fibroblasts, and miR-155 downregulates proteins in the fibroblasts that protect from inflammation and promote fibroblast proliferation. The resulting impairment leads to cardiac rupture [204].
We have already discussed how the S1 segment of the spike protein can be cleaved by furin and released into circulation. It binds to ACE2 receptors through its receptor binding domain (RBD), and this inhibits their function. Because ACE2 degrades Ang II, disabling ACE2 leads directly to overexpression of Ang II, further enhancing risk to cardiovascular disease. AngII-induced vasoconstriction is an independent mechanism to induce permanent myocardial injury even when coronary obstruction is not present. Repeated episodes of sudden constriction of a cardiac artery due to Ang II can eventually lead to heart failure or sudden death [205].
ACE2 suppression had already been seen in studies on the original SARS-CoV virus. An autopsy study on patients succumbing to SARS-CoV revealed an important role for ACE2 inhibition in promoting heart damage. SARS-CoV viral RNA was detected in 35% of 20 autopsied human heart samples taken from patients who died. There was a marked increase in macrophage infiltration associated with myocardial damage in the patients whose hearts were infected with SARS-CoV. Importantly, the presence of SARS- CoV in the heart was associated with marked reduction in ACE2 protein expression [206].