A humanized mouse model of chronic COVID-19
- PMID: 34921308
- PMCID: PMC9203605
- DOI: 10.1038/s41587-021-01155-4
A humanized mouse model of chronic COVID-19
Abstract
Coronavirus disease 2019 (COVID-19) is an infectious disease that can present as an uncontrolled, hyperactive immune response, causing severe immunological injury. Existing rodent models do not recapitulate the sustained immunopathology of patients with severe disease. Here we describe a humanized mouse model of COVID-19 that uses adeno-associated virus to deliver human ACE2 to the lungs of humanized MISTRG6 mice. This model recapitulates innate and adaptive human immune responses to severe acute respiratory syndrome coronavirus 2 infection up to 28 days after infection, with key features of chronic COVID-19, including weight loss, persistent viral RNA, lung pathology with fibrosis, a human inflammatory macrophage response, a persistent interferon-stimulated gene signature and T cell lymphopenia. We used this model to study two therapeutics on immunopathology, patient-derived antibodies and steroids and found that the same inflammatory macrophages crucial to containing early infection later drove immunopathology. This model will enable evaluation of COVID-19 disease mechanisms and treatments.
© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.
Conflict of interest statement
Competing financial interests
RAF is an advisor to Glaxo Smith Kline and Zai Lab.
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A humanized mouse model of chronic COVID-19 to evaluate disease mechanisms and treatment options.Res Sq [Preprint]. 2021 Mar 17:rs.3.rs-279341. doi: 10.21203/rs.3.rs-279341/v1. Res Sq. 2021. Update in: Nat Biotechnol. 2022 Jun;40(6):906-920. doi: 10.1038/s41587-021-01155-4. PMID: 33758831 Free PMC article. Updated. Preprint.
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