Myocardial Injury and Altered Gene Expression Associated with SARS-CoV-2 Infection or mRNA Vaccination

Objectives: To investigate and compare histopathologic characteristics and candidate gene expression in myocardial injury associated with COVID-19 infection and mRNA vaccines.Background: COVID-19 and mRNA vaccines are associated with myocardial injury, via unknown pathophysiologic mechanisms.Methods: Biomarkers, cardiac imaging, myocardial biopsy, light and electron microscopy and measurement of candidate gene (N=7) mRNA expression by RT-qPCR were used to investigate patients with COVID-19 (N=7) or post-mRNA vaccine (N=6) myocardial injury. Gene expression was compared to biobanked control Nonfailing (NF) or Failing (F) explanted hearts or endomyocardial biopsies from a previous study.Results: Histopathology findings in theCOVID-19 patients included a lymphocytic/macrophage infiltrate with myocyte damage in 1, nonspecific abnormalities in 4 and no abnormalities in 2. Of 4 biopsied post-vaccine patients 1 had microvascular thrombosis, and 3 had nonspecific abnormalities. Compared to NF explanted control samples, COVID-19 patients exhibited reduced expression in ACE2, by -2.7 fold (P=0.007); ACE2/ACE ratio, by -7.9 fold (P=0.002); AGTR1, by -2.7 fold (P=0.036); and ITGA5, by -1.7 fold (P=0.006). ACE, by 2.8 fold (P=0.023); and F3 (tissue factor), by 2.6 fold (P=0.026) exhibited increased expression. Post-vaccination patient gene expression yielded a near-identical pattern, and linear discriminant analysis had a probability of 97.8% for membership in the COVID-19 group, compared to 1.9% and 0.2% in the NF and F groups, respectively.Conclusions: A similar pattern of abnormal gene expression is present in myocardial injury associated with COVID-19 and mRNA vaccination, likely mediated by Spike protein and potentially predisposing to cardiac dysfunction, inflammation and coagulopathy.