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

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

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