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.
Highlights
V Overall, our study demonstrates that the Omicron variant is attenuated in virus replication PRE and pathogenicity in mice in comparison with WT and previous variants
Our results demonstrate T that the replication capacity of the Omicron variant is significantly attenuated both in vitro and in A vivo compared with SARS-CoV-2 WT and variant of concern (VOC), which is explained by its lowered efficiency ER of transmembrane serine protease 2 (TMPRSS2) usage
ACC by comparing body weight loss and survival, our results suggest that the Omicron variant is attenuated in pathogenicity when compared with SARS-CoV-2 WT and previous VOCs including Alpha, Beta, and Delta
Summary
ASAttReSn-uCaotVe-d2rBe.p1.l1ic.5a2t9ioOnmanicdrpoanthogenicVitIyEofW Received:23December2021 E Accepted: 19 January 2022 R Accelerated Article Preview Published online 21 January 2022. Attenuated replication and pathogenicity of SARS-CoV-2 B.1.1.529 Omicron Huiping Shuai[1,12], Jasper Fuk-Woo Chan[1,12], Bingjie Hu1,12, Yue Chai[1,12], Terrence Tsz-Tai. W Yuen[1,12], Feifei Yin[2,3,4,12], Xiner Huang[1], Chaemin Yoon[1], Jing-Chu Hu5, Huan Liu[1], Jialu Shi[1], IE Yuanchen Liu[1], Tianrenzheng Zhu[1], Jinjin Zhang[1], Yuxin Hou[1], Yixin Wang[1], Lu Lu1, Jian-Piao V Cai[1], Anna Jinxia Zhang[1,6], Jie Zhou[1,6], Shuofeng Yuan[1,6,7], Melinda A. ACC by comparing body weight loss and survival, our results suggest that the Omicron variant is attenuated in pathogenicity when compared with SARS-CoV-2 WT and previous VOCs including Alpha, Beta, and Delta
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