Attenuated replication and pathogenicity of SARS-CoV-2 B.1.1.529 Omicron

Huiping Shuai, Jasper Fuk-Woo Chan, Bingjie Hu, Yue Chai, Terrence Tsz-Tai Yuen, Feifei Yin, Xiner Huang, Chaemin Yoon, Jing-Chu Hu, Huan Liu, Jialu Shi, Yuanchen Liu, Tianrenzheng Zhu, Jinjin Zhang, Yuxin Hou, Yixin Wang, Lu Lu, Jian-Piao Cai, Anna Jinxia Zhang, Jie Zhou, Shuofeng Yuan, Melinda A. Brindley, Bao-Zhong Zhang, Jian-Dong Huang, Kelvin Kai-Wang To, Kwok-Yung Yuen () and Hin Chu ()
Additional contact information
Huiping Shuai: The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region
Jasper Fuk-Woo Chan: The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region
Bingjie Hu: The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region
Yue Chai: The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region
Terrence Tsz-Tai Yuen: The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region
Feifei Yin: Hainan Medical University
Xiner Huang: The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region
Chaemin Yoon: The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region
Jing-Chu Hu: Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences
Huan Liu: The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region
Jialu Shi: The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region
Yuanchen Liu: The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region
Tianrenzheng Zhu: The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region
Jinjin Zhang: The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region
Yuxin Hou: The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region
Yixin Wang: The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region
Lu Lu: The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region
Jian-Piao Cai: The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region
Anna Jinxia Zhang: The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region
Jie Zhou: The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region
Shuofeng Yuan: The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region
Melinda A. Brindley: University of Georgia
Bao-Zhong Zhang: Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences
Jian-Dong Huang: The University of Hong Kong
Kelvin Kai-Wang To: The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region
Kwok-Yung Yuen: The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region
Hin Chu: The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region

Nature, 2022, vol. 603, issue 7902, 693-699

Abstract: Abstract The Omicron (B.1.1.529) variant of SARS-CoV-2 emerged in November 2021 and is rapidly spreading among the human population1. Although recent reports reveal that the Omicron variant robustly escapes vaccine-associated and therapeutic neutralization antibodies2–10, the pathogenicity of the virus remains unknown. Here we show that the replication of Omicron is substantially attenuated in human Calu3 and Caco2 cells. Further mechanistic investigations reveal that Omicron is inefficient in its use of transmembrane serine protease 2 (TMPRSS2) compared with wild-type SARS-CoV-2 (HKU-001a) and previous variants, which may explain its reduced replication in Calu3 and Caco2 cells. The replication of Omicron is markedly attenuated in both the upper and lower respiratory tracts of infected K18-hACE2 mice compared with that of the wild-type strain and Delta (B.1.617.2) variant, resulting in its substantially ameliorated lung pathology. Compared with wild-type SARS-CoV-2 and the Alpha (B.1.1.7), Beta (1.351) and Delta variants, infection by Omicron causes the lowest reduction in body weight and the lowest mortality rate. Overall, our study demonstrates that the replication and pathogenicity of the Omicron variant of SARS-CoV-2 in mice is attenuated compared with the wild-type strain and other variants.

Date: 2022
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DOI: 10.1038/s41586-022-04442-5

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