Feed

Cardiac complications are common and clinically significant in COVID-19, yet their underlying molecular drivers remain poorly understood. Here, we integrate post-mortem histopathology with transcriptomic and microRNA (miRNA) analyses to delineate the regulatory architecture of SARS-CoV-2-induced myocardial injury. Histological examination of cardiac tissue from 29 deceased COVID-19 patients revealed pronounced immune infiltration, cardiomyocyte necrosis, and fibrotic remodeling. To gain new insights into these pathological processes, we first analyzed 42 transcriptomes from SARS-CoV-2-infected cardiomyocytes, including primary human, iPSC, and hESC-derived cells. We identified 871 differentially expressed genes (DEGs) in infected cardiomyocytes associated with immune activation, extracellular matrix (ECM) remodeling, and impaired contractile function. Based on these dysregulated genes, we then inferred miRNA-mRNA regulatory networks and, through miRTarBase analysis, we uncovered 331 miRNAs as putative regulators of these DEGs, including miR-29a, miR-145, and miR-199a, known to modulate fibrosis, ECM composition, and cardiomyocyte survival. Finally, selected candidates were evaluated in blood samples from COVID-19 patients. We profiled circulating miRNAs in plasma from COVID-19 patients and detected 32 dysregulated miRNAs, 11 of which overlapped with the predicted set. Notably, downregulation of miR-29a correlated with profibrotic signatures, while immune-regulatory miR-21 was upregulated in mild disease. Together, our multi-modal analysis reveals a miRNA-mRNA regulatory program orchestrating inflammation, fibrosis, and contractile dysfunction in the SARS-CoV-2-infected heart. These findings highlight molecular candidates for risk stratification and therapeutic targeting in COVID-19-associated cardiomyopathy.