SARS-CoV-2 infects human pluripotent stem cell-derived cardiomyocytes, impairing electrical and mechanical function

Marchiano, S.; Hsiang, T.-Y.; Higashi, T.; Kanna, A.; Reinecke, H.; Yang, X.; Pabon, L.; Sniadecki, N. J.; Bertero, A.; Gale, M.; Murry, C. E.

doi:10.1101/2020.08.30.274464

bioRxiv · 10.1101/2020.08.30.274464

SARS-CoV-2 infects human pluripotent stem cell-derived cardiomyocytes, impairing electrical and mechanical function

Marchiano, S.·Hsiang, T.-Y.·Higashi, T.·Kanna, A.·Reinecke, H.·Yang, X.·Pabon, L.·Sniadecki, N. J.·Bertero, A.·Gale, M.·Murry, C. E.

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Abstract

Global health has been threatened by the COVID-19 pandemic, caused by the novel severe acute respiratory syndrome coronavirus (SARS-CoV-2)1. Although considered primarily a respiratory infection, many COVID-19 patients also suffer severe cardiovascular disease2-4. Improving patient care critically relies on understanding if cardiovascular pathology is caused directly by viral infection of cardiac cells or indirectly via systemic inflammation and/or coagulation abnormalities3,5-9. Here we examine the cardiac tropism of SARS-CoV-2 using human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) and three-dimensional engineered heart tissues (3D-EHTs). We observe that hPSC-CMs express the viral receptor ACE2 and other viral processing factors, and that SARS-CoV-2 readily infects and replicates within hPSC-CMs, resulting in rapid cell death. Moreover, infected hPSC-CMs show a progressive impairment in both electrophysiological and contractile properties. Thus, COVID-19-related cardiac symptoms likely result from a direct cardiotoxic effect of SARS-CoV-2. Long-term cardiac complications might be possible sequelae in patients who recover from this illness.

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Marchiano, S., Hsiang, T.-Y., Higashi, T., Kanna, A., Reinecke, H., Yang, X., Pabon, L., Sniadecki, N. J., Bertero, A., Gale, M., Murry, C. E.. 2020-08-30. SARS-CoV-2 infects human pluripotent stem cell-derived cardiomyocytes, impairing electrical and mechanical function. https://doi.org/10.1101/2020.08.30.274464

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