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

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

  • Nature. 2022 Mar;603(7902):693-699. doi: 10.1038/s41586-022-04442-5.
Huiping Shuai  # 1,  Jasper Fuk-Woo Chan  # 1,  Bingjie Hu  # 1,  Yue Chai  # 1,  Terrence Tsz-Tai Yuen  # 1,  Feifei Yin  # 2 3 4,  Xiner Huang 1,  Chaemin Yoon 1,  Jing-Chu Hu 5,  Huan Liu 1,  Jialu Shi 1,  Yuanchen Liu 1,  Tianrenzheng Zhu 1,  Jinjin Zhang 1,  Yuxin Hou 1,  Yixin Wang 1,  Lu Lu 1,  Jian-Piao Cai 1,  Anna Jinxia Zhang 1 6,  Jie Zhou 1 6,  Shuofeng Yuan 1 6 7,  Melinda A Brindley 8,  Bao-Zhong Zhang 5,  Jian-Dong Huang 9,  Kelvin Kai-Wang To 1 6 7 10 11,  Kwok-Yung Yuen 12 13 14 15 16 17 18,  Hin Chu 19 20 21
Affiliations

Affiliations

  • 1 State Key Laboratory of Emerging Infectious Diseases, Department of Microbiology, and Carol Yu Centre for Infection, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, Hong Kong, People's Republic of China.
  • 2 Key Laboratory of Tropical Translational Medicine of Ministry of Education, Hainan Medical University, Haikou, China.
  • 3 Academician Workstation of Hainan Province, Hainan Medical University, Haikou, People's Republic of China.
  • 4 Hainan Medical University, The University of Hong Kong Joint Laboratory of Tropical Infectious Diseases, The University of Hong Kong, Hong Kong, China.
  • 5 CAS Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, People's Republic of China.
  • 6 Centre for Virology, Vaccinology and Therapeutics, Hong Kong Science and Technology Park, Hong Kong, People's Republic of China.
  • 7 Department of Clinical Microbiology and Infection Control, The University of Hong Kong-Shenzhen Hospital, Shenzhen, People's Republic of China.
  • 8 Department of Infectious Diseases, Department of Population Health, College of Veterinary Medicine, University of Georgia, Athens, GA, USA.
  • 9 School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, People's Republic of China.
  • 10 Department of Microbiology, Queen Mary Hospital, Hong Kong, People's Republic of China.
  • 11 Guangzhou Laboratory, Guangzhou, China.
  • 12 State Key Laboratory of Emerging Infectious Diseases, Department of Microbiology, and Carol Yu Centre for Infection, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, Hong Kong, People's Republic of China. [email protected].
  • 13 Academician Workstation of Hainan Province, Hainan Medical University, Haikou, People's Republic of China. [email protected].
  • 14 Hainan Medical University, The University of Hong Kong Joint Laboratory of Tropical Infectious Diseases, The University of Hong Kong, Hong Kong, China. [email protected].
  • 15 Centre for Virology, Vaccinology and Therapeutics, Hong Kong Science and Technology Park, Hong Kong, People's Republic of China. [email protected].
  • 16 Department of Clinical Microbiology and Infection Control, The University of Hong Kong-Shenzhen Hospital, Shenzhen, People's Republic of China. [email protected].
  • 17 Department of Microbiology, Queen Mary Hospital, Hong Kong, People's Republic of China. [email protected].
  • 18 Guangzhou Laboratory, Guangzhou, China. [email protected].
  • 19 State Key Laboratory of Emerging Infectious Diseases, Department of Microbiology, and Carol Yu Centre for Infection, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, Hong Kong, People's Republic of China. [email protected].
  • 20 Centre for Virology, Vaccinology and Therapeutics, Hong Kong Science and Technology Park, Hong Kong, People's Republic of China. [email protected].
  • 21 Department of Clinical Microbiology and Infection Control, The University of Hong Kong-Shenzhen Hospital, Shenzhen, People's Republic of China. [email protected].
  • # Contributed equally.
PMID: 35062016 DOI: 10.1038/s41586-022-04442-5
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.

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