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SARS-CoV-2 infection of human iPSC-derived cardiac cells predicts novel cytopathic features in hearts of COVID-19 patients

By Juan A PĂ©rez-Bermejo, Serah Kang, Sarah J. Rockwood, Camille R. Simoneau, David A. Joy, Gokul N. Ramadoss, Ana C. Silva, Will R. Flanigan, Huihui Li, Ken Nakamura, Jeffrey D. Whitman, Melanie Ott, Bruce R. Conklin, T.C. McDevitt

Posted 25 Aug 2020
bioRxiv DOI: 10.1101/2020.08.25.265561

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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