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
  • 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. [email protected] [email protected] [email protected].
  • 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.

Products