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Sep 12, 2020;

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

Juan A P��rez-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
Author Information
  1. Juan A P��rez-Bermejo: Gladstone Institutes, San Francisco, CA.
  2. Serah Kang: Gladstone Institutes, San Francisco, CA.
  3. Sarah J Rockwood: Gladstone Institutes, San Francisco, CA.
  4. Camille R Simoneau: Gladstone Institutes, San Francisco, CA.
  5. David A Joy: Gladstone Institutes, San Francisco, CA.
  6. Gokul N Ramadoss: Gladstone Institutes, San Francisco, CA.
  7. Ana C Silva: Gladstone Institutes, San Francisco, CA.
  8. Will R Flanigan: Gladstone Institutes, San Francisco, CA.
  9. Huihui Li: Gladstone Institutes, San Francisco, CA.
  10. Ken Nakamura: Gladstone Institutes, San Francisco, CA.
  11. Jeffrey D Whitman: UCSF Department of Laboratory Medicine, San Francisco, CA.
  12. Melanie Ott: Gladstone Institutes, San Francisco, CA.
  13. Bruce R Conklin: Gladstone Institutes, San Francisco, CA.
  14. Todd C McDevitt: Gladstone Institutes, 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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Grants

  1. P01 HL146366/NHLBI NIH HHS
  2. U01 ES032673/NIEHS NIH HHS
  3. R01 AG065428/NIA NIH HHS
  4. R01 HL130533/NHLBI NIH HHS
  5. DP1 DA038043/NIDA NIH HHS
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