ABSTRACT
COVID-19 causes cardiac dysfunction in up to 50% of patients, but the pathogenesis remains unclear. Infection of human iPSC-derived cardiomyocytes with SARS-CoV-2 revealed robust transcriptomic and morphological signatures of damage in cardiomyocytes. These morphological signatures include a distinct pattern of sarcomere fragmentation, with specific cleavage of thick filaments, and numerous iPSC-cardiomyocytes that lacked nuclear DNA. Human autopsy specimens from COVID-19 patients also displayed marked sarcomeric disruption and similar fragmentation, as well as prevalently enucleated cardiomyocytes. These striking transcriptomic and cytopathic changes provide a roadmap to understand the mechanisms of COVID-19 cardiac damage, search for potential treatments, and determine the basis for prolonged cardiac morbidity observed in this pandemic.
Competing Interest Statement
B.R.C. is a founder of Tenaya Therapeutics (https://www.tenayatherapeutics.com/), a company focused on finding treatments for heart failure, including genetic cardiomyopathies. B.R.C. and T.C.M. hold equity in Tenaya.
