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SARS-CoV-2 Omicron EG.5 and JN.1 induce enhanced pathogenicity in K18-hACE2 mice compared with the early Omicron subvariants

Abstract

The reduced pathogenicity of early SARS-CoV-2 Omicron subvariants in human ACE2-expressing K18-hACE2 mice has posed challenges for assessing vaccine and antiviral efficacy against the Omicron variant with the mouse model. Here we report the enhanced pathogenicity of the Omicron JN.1 and EG.5 lineages in K18-hACE2 mice compared with their ancestors, suggesting the potential of applying these Omicron lineages in the mouse infection model.

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Fig. 1: Pathogenicity of SARS-CoV-2 ancestral strain (WT) and Omicron subvariants in K18-hACE2 mice.
Fig. 2: Cytokines and chemokines expression in SARS-CoV-2-infected K18-hACE2 mice.

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The data that support the findings of this study are available from the corresponding author upon request.

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Acknowledgements

This work is supported by the Theme-Based Research Scheme (Ref: T11-705/21-N), Collaborative Research Grant (Ref: C7145-20G) and Young Collaborative Research Grant (Ref: C6001-22Y) of the Research Grants Council of the HKSAR Government, the Health and Medical Research Fund (Ref: 21200602) of the Health Bureau, the HKSAR Government and the Hong Kong Jockey Club Global Health Institute (HKJCGHI), Hong Kong Special Administrative Region, China. The Centre for Immunology & Infection is supported by grants from InnoHK, an initiative of the Innovation and Technology Commission of the HKSAR Government.

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A.W.H.C. conceptualized the study. M.T.M.H., N.T., R.H.H.C. and M.C.W.C. designed the experiments. M.T.M.H., N.T., J.C.W.H., S.M.S.C. and A.W.H.C. performed experiments. M.T.M.H., N.T., K.P.Y.H., J.M.N., L.L.M.P. and A.W.H.C. analyzed and interpreted the data. M.T.M.H., N.T. and A.W.H.C. wrote the manuscript. All authors provided feedback to improve the manuscript and agreed on the final paper.

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Correspondence to Alex Wing Hong Chin.

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Lab Animal thanks Shannon Stone and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Ho, M.T.M., Te, N., Hui, K.P.Y. et al. SARS-CoV-2 Omicron EG.5 and JN.1 induce enhanced pathogenicity in K18-hACE2 mice compared with the early Omicron subvariants. Lab Anim 55, 147–150 (2026). https://doi.org/10.1038/s41684-026-01708-7

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