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

Juan A. Pérez-Bermejo, View ORCID ProfileSerah Kang, View ORCID ProfileSarah J. Rockwood, View ORCID ProfileCamille R. Simoneau, View ORCID ProfileDavid A. Joy, View ORCID ProfileGokul N. Ramadoss, View ORCID ProfileAna C. Silva, View ORCID ProfileWill R. Flanigan, View ORCID ProfileHuihui Li, View ORCID ProfileKen Nakamura, View ORCID ProfileJeffrey D. Whitman, View ORCID ProfileMelanie Ott, View ORCID ProfileBruce R. Conklin, View ORCID ProfileTodd C. McDevitt
doi: https://doi.org/10.1101/2020.08.25.265561
Juan A. Pérez-Bermejo
1Gladstone Institute of Data Sciences and Biotechnology, University of California, San Francisco, CA
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Serah Kang
2Gladstone Institute of Cardiovascular Disease, University of California, San Francisco, CA
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Sarah J. Rockwood
2Gladstone Institute of Cardiovascular Disease, University of California, San Francisco, CA
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Camille R. Simoneau
3Biomedical Sciences PhD Program, University of California, San Francisco, CA; Gladstone Institute of Virology, University of California, San Francisco, CA
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David A. Joy
4UC Berkeley UCSF Joint Program in Bioengineering, CA; Gladstone Institute of Cardiovascular Disease, University of California, San Francisco, CA
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Gokul N. Ramadoss
5Biomedical Sciences PhD Program, University of California, San Francisco, Gladstone Institute of Data Sciences and Biotechnology, University of California, San Francisco, CA
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Ana C. Silva
2Gladstone Institute of Cardiovascular Disease, University of California, San Francisco, CA
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Will R. Flanigan
6Gladstone Institute of Cardiovascular Disease, University of California, San Francisco, CA; UC Berkeley UCSF Joint Program in Bioengineering, CA
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Huihui Li
7Gladstone Institute of Neurological Disease, University of California, San Francisco, CA
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Ken Nakamura
8Gladstone Institutes, University of California, San Francisco, CA; Department of Neurology, University of California, San Francisco, CA
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Jeffrey D. Whitman
9Department of Laboratory Medicine, University of California, San Francisco
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Melanie Ott
10Gladstone Institutes, University of California, San Francisco, CA
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  • For correspondence: todd.mcdevitt@gladstone.ucsf.edu
Bruce R. Conklin
11Gladstone Institutes, San Francisco, CA; Innovative Genomics Institute, CA; Departments of Ophthalmology, University of California, San Francisco, CA; Departments of Medicine, University of California, San Francisco, CA
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  • For correspondence: todd.mcdevitt@gladstone.ucsf.edu
Todd C. McDevitt
12Gladstone Institutes, University of California, San Francisco, CA; Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA
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  • ORCID record for Todd C. McDevitt
  • For correspondence: todd.mcdevitt@gladstone.ucsf.edu
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ABSTRACT

COVID-19 causes cardiac dysfunction in up to 50% of patients, but the pathogenesis remains unclear. Infection of human iPSC-derived cardiomyocytes with SARS-CoV-2 revealed robust transcriptomic and morphological signatures of damage in cardiomyocytes. These morphological signatures include a distinct pattern of sarcomere fragmentation, with specific cleavage of thick filaments, and numerous iPSC-cardiomyocytes that lacked nuclear DNA. Human autopsy specimens from COVID-19 patients also displayed marked sarcomeric disruption and similar fragmentation, as well as prevalently enucleated cardiomyocytes. These striking transcriptomic and cytopathic changes provide a roadmap to understand the mechanisms of COVID-19 cardiac damage, search for potential treatments, and determine the basis for prolonged cardiac morbidity observed in this pandemic.

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.

Footnotes

  • https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE156754

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license.
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Posted August 25, 2020.
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SARS-CoV-2 infection of human iPSC-derived cardiac cells predicts novel cytopathic features in hearts of COVID-19 patients
Juan A. Pérez-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, Todd C. McDevitt
bioRxiv 2020.08.25.265561; doi: https://doi.org/10.1101/2020.08.25.265561
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SARS-CoV-2 infection of human iPSC-derived cardiac cells predicts novel cytopathic features in hearts of COVID-19 patients
Juan A. Pérez-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, Todd C. McDevitt
bioRxiv 2020.08.25.265561; doi: https://doi.org/10.1101/2020.08.25.265561

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