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

SARS-CoV-2 Omicron emerged in November 2021 and is rapidly spreading among the human population. While recent reports reveal that the Omicron variant robustly escapes from vaccine and therapeutic neutralization antibodies, the pathogenicity of the virus remains unknown.

Here the authors show that the replication of the Omicron variant is dramatically attenuated in Calu3 and Caco2 cells. Further mechanistic investigations reveal that the Omicron variant is inefficient in transmembrane serine protease 2 (TMPRSS2) usage in comparison to that of WT and previous variants, which may explain its reduced replication in Calu3 and Caco2 cells. Omicron replication is markedly attenuated in both the upper and lower respiratory tract of infected K18-hACE2 mice in comparison to that of WT and Delta variant, which results in its dramatically ameliorated lung pathology. When compared with SARS-CoV-2 WT, Alpha, Beta, and Delta variant, infection by the Omicron variant causes the least body weight loss and mortality rate. The authors concluded that overall, their study demonstrates that the Omicron variant is attenuated In virus replication and pathogenicity in mice In comparison with WT and previous variants.
Shuai H, Chan JF, Hu B, Chai Y, Yuen TT, Yin F, Huang X, Yoon C, Hu JC, Liu H, Shi J, Liu Y, Zhu T, Zhang J, Hou Y, Wang Y, Lu L, Cai JP, Zhang AJ, Zhou J, Yuan S, Brindley MA, Zhang BZ, Huang JD, To KK, Yuen KY, Chu H. Attenuated replication and pathogenicity of SARS-CoV-2 B.1.1.529 Omicron. Nature. 2022 Jan 21.

doi: 10.1038/s41586-022-04442-5.