NEW YORK-METRO Analyzing Cellular Pathways to Understand SARS-Cov-2 Related Cardiomyopathy Through Differential Expression Analysis of Single Cell Transcriptomic Data From Infected Human Ipsc-Derived Cardiac Cells

Overview

SARS-CoV-2 infection can cause widespread dysfunction across multiple organs, including the heart. Myocardial dysfunctions have been observed in many patients with COVID-19. T o understand whether COVID-19 can lead to long-term heart disease, I studied transcriptomic profiles from SARS-CoV-2 infected cardiac cells derived from healthy human subject induced pluripotent stem cells (hiPSC). I analyzed four distinct lines of hiPSC derived cardiac cells, uninfected and infected with SARS-CoV-2 in the presence and absence of interleukins (ILs). An integrated data set for the hiPSC’s from all cell lines was clustered by comparing clusters with cells from healthy adult human heart tissue and identified fibroblast-like and ventricular cardiomyocyte clusters – abundantly found cells in the heart. T o understand how SARS-CoV-2 affected gene expression, differentially expressed genes (DEGs) for both cell types between control and SARS-CoV-2 infected cells with and without interleukins (ILs) were calculated. Enrichment analysis on these DEGs identified the dysregulated subcellular pathways (SCPs). SCPs from SARS-CoV-2 infected fibroblast and cardiomyocyte cells were then compared with pathways of corresponding cell-types from the hearts of patients who had dilated and hypertrophic cardiomyopathy. Substantial overlap was found. Specifically, SCPs underlying cellular adhesion, and protrusion dynamics were dysregulated in fibroblasts and energy generation and cellular contraction were dysregulated in cardiomyocytes. The similarity of top ranked pathways dysregulated by SARS-CoV2 infection and cardiomyopathy suggest that COVID-19 can produce changes that could lead to heart failure over time. While most people recover from COVID-19 fully, for some, persistence of these cell-level changes could lead to long term heart disease.