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

Author

Listed:
  • 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
    Hainan Medical University
    Hainan Medical University, The University of Hong Kong Joint Laboratory of Tropical Infectious Diseases, The University of Hong Kong)

  • 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
    Hong Kong Science and Technology Park)

  • Jie Zhou

    (The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region
    Hong Kong Science and Technology Park)

  • Shuofeng Yuan

    (The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region
    Hong Kong Science and Technology Park
    The University of Hong Kong-Shenzhen Hospital)

  • 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
    Hong Kong Science and Technology Park
    The University of Hong Kong-Shenzhen Hospital
    Queen Mary Hospital)

  • Kwok-Yung Yuen

    (The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region
    Hainan Medical University
    Hainan Medical University, The University of Hong Kong Joint Laboratory of Tropical Infectious Diseases, The University of Hong Kong
    Hong Kong Science and Technology Park)

  • Hin Chu

    (The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region
    Hong Kong Science and Technology Park
    The University of Hong Kong-Shenzhen Hospital)

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.

Suggested Citation

  • 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 & J, 2022. "Attenuated replication and pathogenicity of SARS-CoV-2 B.1.1.529 Omicron," Nature, Nature, vol. 603(7902), pages 693-699, March.
    • Handle: RePEc:nat:nature:v:603:y:2022:i:7902:d:10.1038_s41586-022-04442-5
    DOI: 10.1038/s41586-022-04442-5
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    Cited by:

    1. Markus Hoffmann & Lok-Yin Roy Wong & Prerna Arora & Lu Zhang & Cheila Rocha & Abby Odle & Inga Nehlmeier & Amy Kempf & Anja Richter & Nico Joel Halwe & Jacob Schön & Lorenz Ulrich & Donata Hoffmann & , 2023. "Omicron subvariant BA.5 efficiently infects lung cells," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    2. Taha Y. Taha & Irene P. Chen & Jennifer M. Hayashi & Takako Tabata & Keith Walcott & Gabriella R. Kimmerly & Abdullah M. Syed & Alison Ciling & Rahul K. Suryawanshi & Hannah S. Martin & Bryan H. Bach , 2023. "Rapid assembly of SARS-CoV-2 genomes reveals attenuation of the Omicron BA.1 variant through NSP6," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    3. Cai He & Jingyun Yang & Weiqi Hong & Zimin Chen & Dandan Peng & Hong Lei & Aqu Alu & Xuemei He & Zhenfei Bi & Xiaohua Jiang & Guowen Jia & Yun Yang & Yanan Zhou & Wenhai Yu & Cong Tang & Qing Huang & , 2022. "A self-assembled trimeric protein vaccine induces protective immunity against Omicron variant," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    4. Naoko Iwata-Yoshikawa & Masatoshi Kakizaki & Nozomi Shiwa-Sudo & Takashi Okura & Maino Tahara & Shuetsu Fukushi & Ken Maeda & Miyuki Kawase & Hideki Asanuma & Yuriko Tomita & Ikuyo Takayama & Shutoku , 2022. "Essential role of TMPRSS2 in SARS-CoV-2 infection in murine airways," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    5. Yin-Feng Kang & Cong Sun & Jing Sun & Chu Xie & Zhen Zhuang & Hui-Qin Xu & Zheng Liu & Yi-Hao Liu & Sui Peng & Run-Yu Yuan & Jin-Cun Zhao & Mu-Sheng Zeng, 2022. "Quadrivalent mosaic HexaPro-bearing nanoparticle vaccine protects against infection of SARS-CoV-2 variants," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    6. Mingxi Li & Yifei Ren & Zhen Qin Aw & Bo Chen & Ziqing Yang & Yuqing Lei & Lin Cheng & Qingtai Liang & Junxian Hong & Yiling Yang & Jing Chen & Yi Hao Wong & Jing Wei & Sisi Shan & Senyan Zhang & Jiwa, 2022. "Broadly neutralizing and protective nanobodies against SARS-CoV-2 Omicron subvariants BA.1, BA.2, and BA.4/5 and diverse sarbecoviruses," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    7. Shaofeng Deng & Ying Liu & Rachel Chun-Yee Tam & Pin Chen & Anna Jinxia Zhang & Bobo Wing-Yee Mok & Teng Long & Anja Kukic & Runhong Zhou & Haoran Xu & Wenjun Song & Jasper Fuk-Woo Chan & Kelvin Kai-W, 2023. "An intranasal influenza virus-vectored vaccine prevents SARS-CoV-2 replication in respiratory tissues of mice and hamsters," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    8. Lei Liu & Lijingyao Zhang & Xinyan Hao & Yang Wang & Xiaochun Zhang & Liang Ge & Peihui Wang & Boxue Tian & Min Zhang, 2024. "Coronavirus envelope protein activates TMED10-mediated unconventional secretion of inflammatory factors," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    9. Xiaolei Wang & Terrence Tsz-Tai Yuen & Ying Dou & Jingchu Hu & Renhao Li & Zheng Zeng & Xuansheng Lin & Huarui Gong & Celia Hoi-Ching Chan & Chaemin Yoon & Huiping Shuai & Deborah Tip-Yin Ho & Ivan Fa, 2023. "Vaccine-induced protection against SARS-CoV-2 requires IFN-γ-driven cellular immune response," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    10. Zhuoying Huang & Shuangfei Xu & Jiechen Liu & Linlin Wu & Jing Qiu & Nan Wang & Jia Ren & Zhi Li & Xiang Guo & Fangfang Tao & Jian Chen & Donglei Lu & Yuheng Wang & Juan Li & Xiaodong Sun & Weibing Wa, 2023. "Effectiveness of inactivated COVID-19 vaccines among older adults in Shanghai: retrospective cohort study," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    11. Bruno A. Rodriguez-Rodriguez & Grace O. Ciabattoni & Ralf Duerr & Ana M. Valero-Jimenez & Stephen T. Yeung & Keaton M. Crosse & Austin R. Schinlever & Lucie Bernard-Raichon & Joaquin Rodriguez Galvan , 2023. "A neonatal mouse model characterizes transmissibility of SARS-CoV-2 variants and reveals a role for ORF8," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    12. Han, Lili & Song, Sha & Pan, Qiuhui & He, Mingfeng, 2023. "The impact of multiple population-wide testing and social distancing on the transmission of an infectious disease," Physica A: Statistical Mechanics and its Applications, Elsevier, vol. 630(C).

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