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.