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Science translational medicine
04 21, 2021;13 (590):

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

Juan A Perez-Bermejo, Serah Kang, Sarah J Rockwood, Camille R Simoneau, David A Joy, Ana C Silva, Gokul N Ramadoss, Will R Flanigan, Parinaz Fozouni, Huihui Li, Pei-Yi Chen, Ken Nakamura, Jeffrey D Whitman, Paul J Hanson, Bruce M McManus, Melanie Ott, Bruce R Conklin, Todd C McDevitt
Author Information
  1. Juan A Perez-Bermejo: Gladstone Institutes, San Francisco, CA 94158, USA. ORCID
  2. Serah Kang: Gladstone Institutes, San Francisco, CA 94158, USA. ORCID
  3. Sarah J Rockwood: Gladstone Institutes, San Francisco, CA 94158, USA. ORCID
  4. Camille R Simoneau: Gladstone Institutes, San Francisco, CA 94158, USA. ORCID
  5. David A Joy: Gladstone Institutes, San Francisco, CA 94158, USA. ORCID
  6. Ana C Silva: Gladstone Institutes, San Francisco, CA 94158, USA.
  7. Gokul N Ramadoss: Gladstone Institutes, San Francisco, CA 94158, USA. ORCID
  8. Will R Flanigan: Gladstone Institutes, San Francisco, CA 94158, USA. ORCID
  9. Parinaz Fozouni: Gladstone Institutes, San Francisco, CA 94158, USA. ORCID
  10. Huihui Li: Gladstone Institutes, San Francisco, CA 94158, USA. ORCID
  11. Pei-Yi Chen: Gladstone Institutes, San Francisco, CA 94158, USA. ORCID
  12. Ken Nakamura: Gladstone Institutes, San Francisco, CA 94158, USA. ORCID
  13. Jeffrey D Whitman: Department of Laboratory Medicine, UCSF, San Francisco, CA 94143, USA. ORCID
  14. Paul J Hanson: Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC V6Z 1Y6, Canada. ORCID
  15. Bruce M McManus: Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC V6Z 1Y6, Canada.
  16. Melanie Ott: Gladstone Institutes, San Francisco, CA 94158, USA. todd.mcdevitt@gladstone.ucsf.edu bconklin@gladstone.ucsf.edu melanie.ott@gladstone.ucsf.edu. ORCID
  17. Bruce R Conklin: Gladstone Institutes, San Francisco, CA 94158, USA. todd.mcdevitt@gladstone.ucsf.edu bconklin@gladstone.ucsf.edu melanie.ott@gladstone.ucsf.edu. ORCID
  18. Todd C McDevitt: Gladstone Institutes, San Francisco, CA 94158, USA. todd.mcdevitt@gladstone.ucsf.edu bconklin@gladstone.ucsf.edu melanie.ott@gladstone.ucsf.edu. ORCID
PMID: 33723017 DOI: 10.1126/scitranslmed.abf7872

Abstract

Although coronavirus disease 2019 (COVID-19) causes cardiac dysfunction in up to 25% of patients, its pathogenesis remains unclear. Exposure of human induced pluripotent stem cell (iPSC)-derived heart cells to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) revealed productive infection and robust transcriptomic and morphological signatures of damage, particularly in cardiomyocytes. Transcriptomic disruption of structural genes corroborates adverse morphologic features, which included a distinct pattern of myofibrillar fragmentation and nuclear disruption. Human autopsy specimens from patients with COVID-19 reflected similar alterations, particularly sarcomeric fragmentation. These notable cytopathic features in cardiomyocytes provide insights into SARS-CoV-2-induced cardiac damage, offer a platform for discovery of potential therapeutics, and raise concerns about the long-term consequences of COVID-19 in asymptomatic and severe cases.

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Grants

  1. P01 HL089707/NHLBI NIH HHS
  2. R38 HL143581/NHLBI NIH HHS
  3. P01 HL146366/NHLBI NIH HHS
  4. /European Research Council
  5. T32 GM007618/NIGMS NIH HHS
  6. U01 ES032673/NIEHS NIH HHS
  7. 5DP1 DA038043/NIH HHS
  8. R01 HL130533/NHLBI NIH HHS
  9. R01 HL135358/NHLBI NIH HHS
  10. DP1 DA038043/NIDA NIH HHS
  11. /American Heart Association-American Stroke Association
  12. R01 AG065428/NIA NIH HHS
  13. 1R01 AG065428/NIH HHS

MeSH Term

Autopsy
COVID-19
Cells, Cultured
Heart
Humans
Induced Pluripotent Stem Cells
Myocardium
Myocytes, Cardiac
SARS-CoV-2
Transcriptome
Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

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