Can sarcopenia index serve as a predictor of myocarditis from mRNA based COVID-19 vaccine, insights from clustered cases and potential involvement of micro-RNAs in its pathogenesis.

Abstract

Background: With the current mass international roll out of several vaccines against SARS-Cov-2, several reports of unheeded complications have made headlines. One of which involves myocarditis with the now FDA fully approved vaccine, Pfizer, and others. We hypothesize through this study that a dysregulated micro-RNA response resulting from such type of vaccines can be involved in triggering myocarditis. Methodology: Embase, Medline and the Cochrane Central Register were used to search for specific keywords such as “mRNA COVID-19 vaccines” AND “Myocarditis” for relevant publications up to 1st of September 2021. The systematic review was performed using PRISMA protocolResults:Literature review has identified 26 cases series and reports involving the development of myocarditis from mRNA vaccines, a total of 89 patients were included. Age range was clearly identified in 66 patients. Among those 66 patients, 94% were below 50 years of age, also out of 89 patients, 94% were males. Myocarditis developed, after a median time of 72 hours of the 2nd dose. 90 of cases of myocarditis developed myocarditis after the 2nd dose, the few patients developing myocarditis after the first dose were either predisposed by a history of myocarditis or a history of previous COVID-19 infection. Conclusion:In conclusion, interpretation of the results in view of the suggested hypothesis, reveals that the micro-RNAs implicated in myocarditis in general are as well implicated in the pathogenesis of severe COVID-19, this can explain why patients having a first dose with a history of COVID-19 can develop myocarditis from mRNA vaccines, also the relatively higher likelihood of this complication in males and younger aged individuals can be explained by the upregulation of key myocarditis related miRNAs in those two strata, due to higher muscle mass and suggests performing a sarcopenia index in recipients of the vaccine to correlate it with the likelihood of this complication. This could later set a cut-off of this easy bed-side index to stratify cases a higher risk of this rare complication.

Myopericarditis in a Male Adolescent Following the Second Shot of COVID-19 Pfizer m-RNA Vaccine: Typical Example and Analysis of 110 Single Case Reports

“…Several mechanisms have been suggested, but none is convincing on its own. The many suggested mechanisms include: hyper immune or inflammatory reaction after exposure to spike protein, mRNA strand, or unexplained trigger; late onset of hypersensitivity (serum sickness); eosinophilic myocarditis; hyperreactivity to vaccine excipients (e.g., polyethylene glycol and tromethamine or lipid nanoparticle sheath); reaction to mRNA vaccine lipid nanomolecules; self-immunity through mimicry or other pathways; low residual quantity of double strand RNA; unbalanced micro-RNA reaction; release of anti-idiotype antibodies against certain regions of antigen-specific antibodies; activation of pre-existent dysregulated immune pathways in predisposed subjects (leading to polyclonal B cell growth, immune complex development, and inflammation); antibody-dependent amplification of immunity or other forms of immune intensification with re-exposure to the virus after vaccine inoculation; direct cell invasion through the interplay of the spike protein and the angiotensin converting enzyme 2 (ACE2) widely expressed on cardiomyocytes surfaces; cardiac pericyte expression of ACE2 with disabled immune complex on the surface of pericytes along with activation of the complement system; hyperviscosity-induced cardiac problem; and demanding effort induced secretion of proinflammatory interleukin 6 [ 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 ]. A combination of some of these immune-mediated mechanisms is likely involved in m-RNA vaccine-induced myocarditis and pericarditis, of which the first manifestation can be fatal.…”