Modeling Cardiac SARS-CoV-2 Infection with Human Pluripotent Stem Cells

ABSTRACT: Although SARS-CoV-2, the causative virus of the global COVID-19 pandemic, primarily affects the respiratory tract, it is now recognized to have broad multi-organ tropism and systemic effects. Early reports indicated that SARS-CoV-2 infection could lead to cardiac damage, suggesting the virus may directly impact the heart. Cardiac cell types derived from human pluripotent stem cells (hPSCs) enable mechanistic interrogation of SARS-CoV-2 infection in human cardiac tissue. PURPOSE OF REVIEW: To review the studies published since the emergence of the COVID-19 pandemic which utilize hPSCs and their cardiovascular derivative cell types to interrogate the tropism and effects of SARS-CoV-2 infection in the heart, as well as explore potential therapies. RECENT FINDINGS: Recent studies reveal that SARS-CoV-2 is capable of infecting and replicating within hPSC-derived cardiomyocytes and sinoatrial nodal cells, but not as extensively in their non-parenchymal counterparts. Additionally, they show striking viral effects on cardiomyocyte structure, transcriptional activity, and survival, along with potential mechanisms and therapeutic targets. SUMMARY: Cardiac models derived from hPSCs are a viable platform to study the impact of SARS-CoV-2 on cardiac tissue and may lead to novel mechanistic insight as well as therapeutic interventions.