SARS-CoV-2 variants divergently infect and damage cardiomyocytes in vitro and in vivo
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Published:2024-08-02
Issue:1
Volume:14
Page:
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ISSN:2045-3701
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Container-title:Cell & Bioscience
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language:en
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Short-container-title:Cell Biosci
Author:
Mok Bobo Wing-Yee, Kwok Maxwell, Li Hung Sing, Ling Lowell, Lai Angel, Yan Bin, Law Cherie Tsz-Yiu, Yeung Chui Him, Zhang Anna Jinxia, Tam Rachel Chun-Yee, Kukic Anja, Cremin Conor J., Zhang Yajie, Long Teng, Kang Zhisen, Luo Ruibang, Leung Kam Tong, Li Albert M., Lui Grace, Tsui Stephen Kwok-Wing, Chan Jasper Fuk-Woo, To Kelvin Kai-Wang, Chan Paul K. S., Yan Bryan P., Chen Honglin, Poon Ellen Ngar-YunORCID
Abstract
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.
Funder
Hong Kong Research Grants Council Chinese University of Hong Kong Sun Chieh Yeh Heart Foundation Research Grant Hong Kong Health and Medical Research Fund
Publisher
Springer Science and Business Media LLC
Reference61 articles.
1. To KK, Sridhar S, Chiu KH, Hung DL, Li X, Hung IF, Tam AR, Chung TW, Chan JF, Zhang AJ, et al. Lessons learned 1 year after SARS-CoV-2 emergence leading to COVID-19 pandemic. Emerg Microbes Infect. 2021;10(1):507–35. 2. Viana R, Moyo S, Amoako DG, Tegally H, Scheepers C, Althaus CL, Anyaneji UJ, Bester PA, Boni MF, Chand M, et al. Rapid epidemic expansion of the SARS-CoV-2 Omicron variant in southern Africa. Nature. 2022;603(7902):679–86. 3. Cheng VCC, Ip JD, Chu AWH, Tam AR, Chan WM, Abdullah SMU, Chan BPC, Wong SC, Kwan MYW, Chua GT, et al. Rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron subvariant BA.2 in a single-source community outbreak. Clin Infect Dis. 2022;75(1):e44–9. 4. Hui KPY, Ho JCW, Cheung MC, Ng KC, Ching RHH, Lai KL, Kam TT, Gu H, Sit KY, Hsin MKY, et al. SARS-CoV-2 Omicron variant replication in human bronchus and lung ex vivo. Nature. 2022;603(7902):715–20. 5. Meng B, Abdullahi A, Ferreira I, Goonawardane N, Saito A, Kimura I, Yamasoba D, Gerber PP, Fatihi S, Rathore S, et al. Altered TMPRSS2 usage by SARS-CoV-2 Omicron impacts infectivity and fusogenicity. Nature. 2022;603(7902):706–14.
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