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].