Comparison of the pathogenicity and neutrophil and monocyte response between SARS-CoV-2 prototype and Omicron BA.1 in a lethal mouse model  

作　　者：Na Rong Jing Wu Binbin Zhao Wanjun Peng Hekai Yang Gengxin Zhang Dangting Ruan Xiaohui Wei Jiangning Liu 

机构地区：[1]NHC Key Laboratory of Human Disease Comparative Medicine,Beijing Key Laboratory for Animal Models of Emerging and Reemerging Infectious Diseases,State Key Laboratory of Respiratory Health and Multimorbidity,Institute of Laboratory Animal Science,Chinese Academy of Medical Sciences and Comparative Medicine Center,Peking Union Medical College,Beijing,China [2]Wuhan Servicebio Technology Co.,Ltd.,Wuhan,China

出　　处：《Animal Models and Experimental Medicine》2025年第4期707-717,共11页动物模型与实验医学(英文)

基　　金：supported by Beijing Natural Science Foundation(Grant No.Z210014);National Natural Science Foundation of China(Grant No.32070543);National Key Research and Development Project of China(Grant No.2022YFC2303404);CAMS Innovation Fund for Medical Sciences(CIFMS)(Grant No.2022-12M-CoV19-002)

摘　　要：Background:SARS-CoV-2,first identified in late 2019,has given rise to numerous variants of concern(VOCs),posing a significant threat to human health.The emer-gence of Omicron BA.1.1 towards the end of 2021 led to a pandemic in early 2022.At present,the lethal mouse model for the study of SARS-CoV-2 needs supplementation,and the alterations in neutrophils and monocytes caused by different strains remain to be elucidated.Methods:Human ACE2 transgenic mice were inoculated with the SARS-CoV-2 proto-type and Omicron BA.1,respectively.The pathogenicity of the two strains was evalu-ated by observing clinical symptoms,viral load and pathology.Complete blood count,immunohistochemistry and flow cytometry were performed to detect the alterations of neutrophils and monocytes caused by the two strains.Results:Our findings revealed that Omicron BA.1 exhibited significantly lower vir-ulence compared to the SARS-CoV-2 prototype in the mouse model.Additionally,we observed a significant increase in the proportion of neutrophils late in infection with the SARS-CoV-2 prototype and Omicron BA.1.We found that the proportion of monocytes increased at first and then decreased.The trends in the changes in the proportions of neutrophils and monocytes induced by the two strains were similar.Conclusion:Our study provides valuable insights into the utility of mouse models for simulating the severe disease of SARS-CoV-2 prototype infection and the milder manifestation associated with Omicron BA.1.SARS-CoV-2 prototype and Omicron BA.1 resulted in similar trends in the changes in neutrophils and monocytes.

关 键 词：animal model SARS-CoV-2 Omicron BA.1 MONOCYTE NEUTROPHIL 

分 类 号：R563.1[医药卫生—呼吸系统]