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Review Open Access

Application of the humanized mouse model in research into SARS-CoV-2 infection (Review)

  • Authors:
    • Xiaoyue Feng
    • Yadong Wang
    • Yuan Li
    • Jinzhao Long
    • Fang Liu
    • Haiyan Yang
  • View Affiliations / Copyright

    Affiliations: Department of Epidemiology, School of Public Health, Zhengzhou University, Zhengzhou, Henan 450001, P.R. China, Department of Toxicology, Henan Center for Disease Control and Prevention, Zhengzhou, Henan 450016, P.R. China
    Copyright: © Feng et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY 4.0].
  • Article Number: 9
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    Published online on: December 29, 2025
       https://doi.org/10.3892/mi.2025.293
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Abstract

The coronavirus disease 2019 (COVID-19) pandemic triggered by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has had a profound impact on global public health. The complexity of its pathogenic mechanisms and host interactions urgently requires high-fidelity animal models to support research. Humanized mouse models break the species barrier through gene editing and immune reconstitution technologies, providing a key tool to simulate human infection characteristics and pathological processes. A number of studies have reported the application of humanized mouse models in the fields of COVID-19 research, such as SARS-CoV-2 pathogenesis, anti-SARS-CoV-2 drug discovery and vaccine development, etc. The present review aimed to systematically document the latest advances in the application of humanized mouse models based on different construction strategies, such as receptor humanization, immune system humanization and composite humanization. These models have not only elucidated the pathogenicity differences and immune escape mechanisms of SARS-CoV-2 variants, but have also validated the efficacy of broad-spectrum anti-SARS-CoV-2 strategies, including angiotensin-converting enzyme 2-targeted therapies, antibody cocktail regimens and mucosal vaccines. Additionally, humanized mouse models have played a pivotal role in investigating the mechanisms underlying long COVID. By revealing the multi-system pathogenic mechanisms of pulmonary fibrosis, neurodegeneration and intestinal microbiota dysregulation, these models provide a theoretical foundation for the development of targeted intervention strategies.
View Figures

Figure 1

The application of the humanized
mouse model in research into severe acute respiratory syndrome
coronavirus 2 infection. COVID-19, coronavirus disease 2019.

Figure 2

Strategies for constructing humanized
mouse models. ACE2, angiotensin-converting enzyme 2; HSCs,
hematopoietic stem cells; MHC, major histocompatibility
complex.
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Feng X, Wang Y, Li Y, Long J, Liu F and Yang H: Application of the humanized mouse model in research into SARS-CoV-2 infection (Review). Med Int 6: 9, 2026.
APA
Feng, X., Wang, Y., Li, Y., Long, J., Liu, F., & Yang, H. (2026). Application of the humanized mouse model in research into SARS-CoV-2 infection (Review). Medicine International, 6, 9. https://doi.org/10.3892/mi.2025.293
MLA
Feng, X., Wang, Y., Li, Y., Long, J., Liu, F., Yang, H."Application of the humanized mouse model in research into SARS-CoV-2 infection (Review)". Medicine International 6.1 (2026): 9.
Chicago
Feng, X., Wang, Y., Li, Y., Long, J., Liu, F., Yang, H."Application of the humanized mouse model in research into SARS-CoV-2 infection (Review)". Medicine International 6, no. 1 (2026): 9. https://doi.org/10.3892/mi.2025.293
Copy and paste a formatted citation
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Spandidos Publications style
Feng X, Wang Y, Li Y, Long J, Liu F and Yang H: Application of the humanized mouse model in research into SARS-CoV-2 infection (Review). Med Int 6: 9, 2026.
APA
Feng, X., Wang, Y., Li, Y., Long, J., Liu, F., & Yang, H. (2026). Application of the humanized mouse model in research into SARS-CoV-2 infection (Review). Medicine International, 6, 9. https://doi.org/10.3892/mi.2025.293
MLA
Feng, X., Wang, Y., Li, Y., Long, J., Liu, F., Yang, H."Application of the humanized mouse model in research into SARS-CoV-2 infection (Review)". Medicine International 6.1 (2026): 9.
Chicago
Feng, X., Wang, Y., Li, Y., Long, J., Liu, F., Yang, H."Application of the humanized mouse model in research into SARS-CoV-2 infection (Review)". Medicine International 6, no. 1 (2026): 9. https://doi.org/10.3892/mi.2025.293
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