SARS-CoV-2 infection of human iPSC-derived cardiac cells predicts novel cytopathic features in hearts of COVID-19 patients
Juan A Pérez-Bermejo,
Sarah J. Rockwood,
Camille R. Simoneau,
David A. Joy,
Gokul N. Ramadoss,
Ana C. Silva,
Will R. Flanigan,
Jeffrey D. Whitman,
Bruce R. Conklin,
Posted 25 Aug 2020
bioRxiv DOI: 10.1101/2020.08.25.265561
Posted 25 Aug 2020
Although COVID-19 causes cardiac dysfunction in up to 25% of patients, its pathogenesis remains unclear. Exposure of human iPSC-derived heart cells to SARS-CoV-2 revealed productive infection and robust transcriptomic and morphological signatures of damage, particularly in cardiomyocytes. Transcriptomic disruption of structural proteins corroborated adverse morphologic features, which included a distinct pattern of myofibrillar fragmentation and numerous iPSC-cardiomyocytes lacking nuclear DNA. Human autopsy specimens from COVID-19 patients displayed similar sarcomeric disruption, as well as cardiomyocytes without DNA staining. These striking cytopathic features provide new insights into SARS-CoV-2 induced cardiac damage, offer a platform for discovery of potential therapeutics, and raise serious concerns about the long-term consequences of COVID-19. ### 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.
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