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

Perez-Bermejo, Juan A.; Kang, Serah; Rockwood, Sarah J.; Simoneau, Camille R.; Joy, David A.; Silva, Ana C.; Ramadoss, Gokul N.; Flanigan, Will R.; Fozouni, Parinaz; Li, Huihui; Chen, Pei-Yi; Nakamura, Ken; Whitman, Jeffrey D.; Hanson, Paul J.; McManus, Bruce M.; Ott, Melanie; Conklin, Bruce R.; McDevitt, Todd C.

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 striking 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 as well as severe cases.