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

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

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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