SARS-CoV-2 variants divergently infect and damage cardiomyocytes in vitro and in vivo

  • Cell Biosci. 2024 Aug 2;14(1):101. doi: 10.1186/s13578-024-01280-y.
Bobo Wing-Yee Mok  #  1  2 ,  Maxwell Kwok  #  3  4  5 ,  Hung Sing Li  #  4  6 ,  Lowell Ling  7 ,  Angel Lai  3  8 ,  Bin Yan  9 ,  Cherie Tsz-Yiu Law  5 ,  Chui Him Yeung  10 ,  Anna Jinxia Zhang  11 ,  Rachel Chun-Yee Tam  11  12 ,  Anja Kukic  11  12 ,  Conor J Cremin  11  12 ,  Yajie Zhang  12 ,  Teng Long  11  12 ,  Zhisen Kang  11  12 ,  Ruibang Luo  9 ,  Kam Tong Leung  4  6 ,  Albert M Li  4  6 ,  Grace Lui  3 ,  Stephen Kwok-Wing Tsui  5 ,  Jasper Fuk-Woo Chan  11  12 ,  Kelvin Kai-Wang To  11  12 ,  Paul K S Chan  13 ,  Bryan P Yan  3  8 ,  Honglin Chen  11  12 ,  Ellen Ngar-Yun Poon  14  15  16  17
Affiliations
  • 1. State Key Laboratory for Emerging Infectious Diseases, Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, SAR, China. [email protected].
  • 2. Centre for Virology, Vaccinology and Therapeutics, Hong Kong Science and Technology Park, Hong Kong, SAR, China. [email protected].
  • 3. Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, SAR, China.
  • 4. Hong Kong Hub of Paediatric Excellence (HK HOPE), The Chinese University of Hong Kong, Hong Kong, SAR, China.
  • 5. The School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, SAR, China.
  • 6. Department of Paediatrics, The Chinese University of Hong Kong, Hong Kong, SAR, China.
  • 7. Department of Anaesthesia and Intensive Care, The Chinese University of Hong Kong, Hong Kong, SAR, China.
  • 8. Heart and Vascular Institute, The Chinese University of Hong Kong, Hong Kong, SAR, China.
  • 9. Department of Computer Science, The University of Hong Kong, Hong Kong, SAR, China.
  • 10. Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, SAR, China.
  • 11. State Key Laboratory for Emerging Infectious Diseases, Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, SAR, China.
  • 12. Centre for Virology, Vaccinology and Therapeutics, Hong Kong Science and Technology Park, Hong Kong, SAR, China.
  • 13. Department of Microbiology, The Chinese University of Hong Kong, Hong Kong, SAR, China.
  • 14. Hong Kong Hub of Paediatric Excellence (HK HOPE), The Chinese University of Hong Kong, Hong Kong, SAR, China. [email protected].
  • 15. The School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, SAR, China. [email protected].
  • 16. Centre for Cardiovascular Genomics and Medicine, Lui Che Woo Institute of Innovative Medicine, The Chinese University of Hong Kong, Hong Kong, SAR, China. [email protected].
  • 17. Ministry of Education Key Laboratory for Regenerative Medicine, The Chinese University of Hong Kong, Hong Kong, SAR, China. [email protected].
  • # Contributed equally.
PMID: 39095802 DOI: 10.1186/s13578-024-01280-y
Abstract

Background: COVID-19 can cause cardiac complications and the latter are associated with poor prognosis and increased mortality. SARS-CoV-2 variants differ in their infectivity and pathogenicity, but how they affect cardiomyocytes (CMs) is unclear.

Methods: The effects of SARS-CoV-2 variants were investigated using human induced pluripotent stem cell-derived (hiPSC-) CMs in vitro and Golden Syrian hamsters in vivo.

Results: Different variants exhibited distinct tropism, mechanism of viral entry and pathology in the heart. Omicron BA.2 most efficiently infected and injured CMs in vitro and in vivo, and induced expression changes consistent with increased cardiac dysfunction, compared to Other variants tested. Bioinformatics and upstream regulator analyses identified transcription factors and network predicted to control the unique transcriptome of Omicron BA.2 infected CMs. Increased infectivity of Omicron BA.2 is attributed to its ability to infect via endocytosis, independently of TMPRSS2, which is absent in CMs.

Conclusions: In this study, we reveal previously unknown differences in how different SARS-CoV-2 variants affect CMs. Omicron BA.2, which is generally thought to cause mild disease, can damage CMs in vitro and in vivo. Our study highlights the need for further investigations to define the pathogenesis of cardiac complications arising from different SARS-CoV-2 variants.

Keywords
COVID-19; Cardiac infection; Cardiomyocytes; Heart; Omicron; SARS-CoV-2.
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