SARS-CoV-2 infection of human iPSC–derived cardiac cells reflects cytopathic features in hearts of patients with COVID-19
Juan A. Pérez-Bermejo, Michael S. Kang, Sarah J. Rockwood, Camille R. Simoneau, David Joy, Ana C. Silva, Gokul N. Ramadoss, Will Flanigan, Parinaz Fozouni, Huihui Li, Peiyi Chen, Ken Nakamura, Jeffrey D. Whitman, Paul Hanson, Bruce M. McManus, Mélanie Ott, Bruce R. Conklin, Todd C. McDevitt
Abstract
Although coronavirus disease 2019 (COVID-19) causes cardiac dysfunction in up to 25% of patients, its pathogenesis remains unclear. Exposure of human induced pluripotent stem cell (iPSC)-derived heart cells to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) revealed productive infection and robust transcriptomic and morphological signatures of damage, particularly in cardiomyocytes. Transcriptomic disruption of structural genes corroborates adverse morphologic features, which included a distinct pattern of myofibrillar fragmentation and nuclear disruption. Human autopsy specimens from patients with COVID-19 reflected similar alterations, particularly sarcomeric fragmentation. These notable cytopathic features in cardiomyocytes provide insights into SARS-CoV-2-induced cardiac damage, offer a platform for discovery of potential therapeutics, and raise concerns about the long-term consequences of COVID-19 in asymptomatic and severe cases.