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

  • bioRxiv. 2020 Sep 12;2020.08.25.265561. doi: 10.1101/2020.08.25.265561.
Juan A Pérez-Bermejo  1 ,  Serah Kang  1 ,  Sarah J Rockwood  1 ,  Camille R Simoneau  1  2 ,  David A Joy  1  3 ,  Gokul N Ramadoss  1  2 ,  Ana C Silva  1 ,  Will R Flanigan  1  3 ,  Huihui Li  1 ,  Ken Nakamura  1  4 ,  Jeffrey D Whitman  5 ,  Melanie Ott  1 ,  Bruce R Conklin  1  6  7  8 ,  Todd C McDevitt  1  9
Affiliations
  • 1. Gladstone Institutes, San Francisco, CA.
  • 2. Biomedical Sciences PhD Program, University of California, San Francisco, CA.
  • 3. UC Berkeley UCSF Joint Program in Bioengineering, Berkeley, CA.
  • 4. UCSF Department of Neurology, San Francisco, CA.
  • 5. UCSF Department of Laboratory Medicine, San Francisco, CA.
  • 6. Innovative Genomics Institute, Berkeley, CA.
  • 7. UCSF Department of Ophthalmology, San Francisco, CA.
  • 8. UCSF Department of Medicine, San Francisco, CA.
  • 9. UCSF Department of Bioengineering and Therapeutic Sciences, San Francisco, CA.
PMID: 32935097 DOI: 10.1101/2020.08.25.265561
Abstract

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.

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