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Comparison of the pathogenicity and neutrophil and monocyte response between SARS-CoV-2 prototype and Omicron BA.1 in
Na Rong1, Jing Wu1, Binbin Zhao1
1NHC 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.
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 emergence 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 prototype and Omicron BA.1, respectively. The pathogenicity of the two strains was evaluated 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 virulence 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.
Insights
SARS-CoV-2 Omicron BA.1 is less virulent than the prototype strain in mice, with both strains causing similar neutrophil and monocyte changes. This research aids in understanding COVID-19 mouse models.
Area of Science:
- Virology
- Immunology
- Pathology
Background:
- Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has produced numerous variants of concern (VOCs).
- The Omicron BA.1.1 variant emerged in late 2021, causing a global pandemic in early 2022.
- Existing lethal mouse models for SARS-CoV-2 require improvement, and immune cell alterations by different strains need further study.
Purpose of the Study:
- To compare the pathogenicity of the SARS-CoV-2 prototype and Omicron BA.1 strains in a human ACE2 transgenic mouse model.
- To investigate the alterations in neutrophils and monocytes induced by these two SARS-CoV-2 strains.
Main Methods:
- Human ACE2 transgenic mice were infected with either the SARS-CoV-2 prototype or Omicron BA.1.
- Pathogenicity was assessed through clinical symptoms, viral load, and tissue pathology.
- Complete blood counts, immunohistochemistry, and flow cytometry analyzed neutrophil and monocyte changes.
Main Results:
- Omicron BA.1 demonstrated significantly lower virulence than the SARS-CoV-2 prototype in the mouse model.
- Both strains led to a late-stage increase in neutrophils.
- Monocyte proportions initially rose before declining, with similar trends observed for both strains.
Conclusions:
- The study validates mouse models for simulating severe SARS-CoV-2 prototype and milder Omicron BA.1 infections.
- Both SARS-CoV-2 prototype and Omicron BA.1 induced comparable alterations in neutrophil and monocyte populations.
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