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

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

  • Sci Transl Med. 2021 Apr 21;13(590):eabf7872. doi: 10.1126/scitranslmed.abf7872.
Juan A Perez-Bermejo 1,  Serah Kang 1,  Sarah J Rockwood 1,  Camille R Simoneau 1 2,  David A Joy 1 3,  Ana C Silva 1,  Gokul N Ramadoss 1 2,  Will R Flanigan 1 3,  Parinaz Fozouni 1 2,  Huihui Li 1,  Pei-Yi Chen 1,  Ken Nakamura 1 4,  Jeffrey D Whitman 5,  Paul J Hanson 6,  Bruce M McManus 6,  Melanie Ott 7 8,  Bruce R Conklin 7 8 9 10,  Todd C McDevitt 7 11
Affiliations

Affiliations

  • 1 Gladstone Institutes, San Francisco, CA 94158, USA.
  • 2 Biomedical Sciences Graduate Program, University of California, San Francisco, San Francisco, CA 94158, USA.
  • 3 UC Berkeley-UCSF Joint Program in Bioengineering, Berkeley, CA 94720, USA.
  • 4 Department of Neurology, UCSF, San Francisco, CA 94143, USA.
  • 5 Department of Laboratory Medicine, UCSF, San Francisco, CA 94143, USA.
  • 6 Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC V6Z 1Y6, Canada.
  • 7 Gladstone Institutes, San Francisco, CA 94158, USA. todd.mcdevitt@gladstone.ucsf.edu bconklin@gladstone.ucsf.edu melanie.ott@gladstone.ucsf.edu.
  • 8 Department of Medicine, UCSF, San Francisco, CA 94143, USA.
  • 9 Innovative Genomics Institute, Berkeley, CA 94704, USA.
  • 10 Department of Ophthalmology, UCSF, San Francisco, CA 94158, USA.
  • 11 Department of Bioengineering and Therapeutic Sciences, UCSF, San Francisco, CA 94158, USA.
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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