TY - JOUR
T1 - Attenuated replication and pathogenicity of SARS-CoV-2 B.1.1.529 Omicron
AU - Shuai, Huiping
AU - Chan, Jasper Fuk Woo
AU - Hu, Bingjie
AU - Chai, Yue
AU - Yuen, Terrence Tsz Tai
AU - Yin, Feifei
AU - Huang, Xiner
AU - Yoon, Chaemin
AU - Hu, Jing Chu
AU - Liu, Huan
AU - Shi, Jialu
AU - Liu, Yuanchen
AU - Zhu, Tianrenzheng
AU - Zhang, Jinjin
AU - Hou, Yuxin
AU - Wang, Yixin
AU - Lu, Lu
AU - Cai, Jian Piao
AU - Zhang, Anna Jinxia
AU - Zhou, Jie
AU - Yuan, Shuofeng
AU - Brindley, Melinda A.
AU - Zhang, Bao Zhong
AU - Huang, Jian Dong
AU - To, Kelvin Kai Wang
AU - Yuen, Kwok Yung
AU - Chu, Hin
N1 - Publisher Copyright:
© 2022, The Author(s), under exclusive licence to Springer Nature Limited.
PY - 2022/3/24
Y1 - 2022/3/24
N2 - 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.
AB - 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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U2 - 10.1038/s41586-022-04442-5
DO - 10.1038/s41586-022-04442-5
M3 - Article
C2 - 35062016
AN - SCOPUS:85123437628
SN - 0028-0836
VL - 603
SP - 693
EP - 699
JO - Nature
JF - Nature
IS - 7902
ER -