A Mouse-Adapted SARS-CoV-2 Induces Acute Lung Injury and Mortality in Standard Laboratory Mice
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The SARS-CoV-2 pandemic has caused extreme human suffering and economic harm. We generated and characterized a new mouse-adapted SARS-CoV-2 virus that captures multiple aspects of severe COVID-19 disease in standard laboratory mice. This SARS-CoV-2 model exhibits the spectrum of morbidity and mortality of COVID-19 disease as well as aspects of host genetics, age, cellular tropisms, elevated Th1 cytokines, and loss of surfactant expression and pulmonary function linked to pathological features of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). This model can rapidly access existing mouse resources to elucidate the role of host genetics, underlying molecular mechanisms governing SARS-CoV-2 pathogenesis, and the protective or pathogenic immune responses related to disease severity. The model promises to provide a robust platform for studies of ALI and ARDS to evaluate vaccine and antiviral drug performance, including in the most vulnerable populations (i.e., the aged) using standard laboratory mice.
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Mouse studies of SARS-CoV-2 show a higher viral burden in older mice during the first days after infection.
“Mouse studies of SARS-CoV-2 show a higher viral burden in older mice in the first few days post-infection”
From SARS-CoV-2, COVID-19 and the aging immune system (2021) · cites this paper as [55]
Ageing may cause a delay or dysfunction in the initial triggering and priming of the immune response to SARS-CoV-2.
“suggesting that aging may also lead to a delay or dysfunction in the initial triggering and priming stages of the immune response54,55”
From SARS-CoV-2, COVID-19 and the aging immune system (2021) · cites this paper as [55]
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Zhang, J., Lee, A. C.-Y., Chu, H., Chan, J. F., Fan, Z., Li, C., Liu, F., Chen, Y., Yuan, S., Poon, V. K., et al. (2020) · Clinical Infectious Diseases · Cited by 24 · see citing works
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An oral SARS-CoV-2 M <sup>pro</sup> inhibitor clinical candidate for the treatment of COVID-19
Owen, D. R., Allerton, C. M. N., Anderson, A. S., Aschenbrenner, L., Avery, M., Berritt, S., Boras, B., Cardin, R. D., Carlo, A., Coffman, K. J., et al. (2021) · Science · doi:10.1126/science.abl4784 · Cited by 2,033 · see citing works
SARS-CoV-2 D614G variant exhibits efficient replication ex vivo and transmission in vivo
Hou, Y. J., Chiba, S., Halfmann, P., Ehre, C., Kuroda, M., Dinnon, K. H., Leist, S. R., Schäfer, A., Nakajima, N., Takahashi, K., et al. (2020) · Science · doi:10.1126/science.abe8499 · Cited by 900 · see citing works
Self-citationStructural basis of SARS-CoV-2 Omicron immune evasion and receptor engagement
McCallum, M., Czudnochowski, N., Rosen, L. E., Zepeda, S. K., Bowen, J. E., Walls, A. C., Hauser, K., Joshi, A., Stewart, C., Dillen, J. R., et al. (2022) · Science · doi:10.1126/science.abn8652 · Cited by 535 · see citing works
“These findings concur with the emergence and fixation of the Q493K RBD mutation upon serial passaging in mice to yield a mouse-adapted virus designated SARS-CoV-2 MA10 ( 50 ).”
Winkler, E. S., Gilchuk, P., Yu, J., Bailey, A. L., Chen, R. E., Chong, Z., Zost, S. J., Jang, H., Huang, Y., Allen, J. D., et al. (2021) · Cell · doi:10.1016/j.cell.2021.02.026 · Cited by 366 · see citing works
SARS-CoV-2, COVID-19 and the aging immune system
Bartleson, J. M., Radenkovic, D., Covarrubias, A. J., Furman, D., Winer, D. A., & Verdin, E. (2021) · Nature Aging · doi:10.1038/s43587-021-00114-7 · Cited by 359 · see citing works
Walls, A. C., Miranda, M. C., Schäfer, A., Pham, M. N., Greaney, A., Arunachalam, P. S., Navarro, M.-J., Tortorici, M. A., Rogers, K., O’Connor, M. A., et al. (2021) · Cell · doi:10.1016/j.cell.2021.09.015 · Cited by 185 · see citing works
“These results indicate that one or two immunizations with 1 mg RBD-NPs results in protection against SARS-CoV-2 MA10-induced disease.”
MethodInfluentialSelf-citationEicosanoid signalling blockade protects middle-aged mice from severe COVID-19
Wong, L.-Y. R., Zheng, J., Wilhelmsen, K., Li, K., Ortiz, M. E., Schnicker, N. J., Thurman, A., Pezzulo, A. A., Szachowicz, P. J., Li, P., et al. (2022) · Nature · doi:10.1038/s41586-022-04630-3 · Cited by 178 · see citing works
Q493K and Q498H substitutions in Spike promote adaptation of SARS-CoV-2 in mice
Huang, K., Zhang, Y., Hui, X., Zhao, Y., Gong, W., Wang, T., Zhang, S., Yang, Y., Deng, F., Zhang, Q., et al. (2021) · EBioMedicine · doi:10.1016/j.ebiom.2021.103381 · Cited by 119 · see citing works
Characterization and structural basis of a lethal mouse-adapted SARS-CoV-2
Sun, S., Gu, H., Cao, L., Chen, Q., Ye, Q., Yang, G., Li, R.-T., Fan, H., Deng, Y.-Q., Song, X., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-25903-x · Cited by 104 · see citing works
Animal models in SARS-CoV-2 research
Chu, H., Chan, J. F.-W., & Yuen, K.-Y. (2022) · Nature Methods · doi:10.1038/s41592-022-01447-w · Cited by 103 · see citing works
Tsuji, S., Minami, S., Hashimoto, R., Konishi, Y., Suzuki, T., Kondo, T., Sasai, M., Torii, S., Ono, C., Shichinohe, S., et al. (2022) · Nature Aging · doi:10.1038/s43587-022-00170-7 · Cited by 84 · see citing works
- Authors
- Leist, S. R., Dinnon, K. H., Schäfer, A., Tse, L. V., Okuda, K., Hou, Y. J., West, A., Edwards, C. E., Sanders, W., Fritch, E. J., Gully, K. L., Scobey, T., Brown, A. J., Sheahan, T. P., Moorman, N. J., Boucher, R. C., Gralinski, L. E., Montgomery, S. A., & Baric, R. S.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- Corresponding author
- Baric, Ralph S.
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2020-11
- Volume
- 183
- Issue
- 4
- Pages
- 1070-1085.e12
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC7510428
- OpenAlex
- W3087207483
- Cited by
- 613
- References
- 78
- Citations by year
- 2026: 47 · 2025: 66 · 2024: 106 · 2023: 105 · 2022: 144 · 2021: 131 · 2020: 14
- FWCI
- 12.91
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 376 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cell (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- ImmPort
- Funders
- National Cancer Institute
- National Institute of Allergy and Infectious Diseases
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
- Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Virus Infections Studies
- Keywords
- SARS-CoV-2, mouse-adapted virus, COVID-19 pandemic, acute lung injury, acute respiratory distress syndrome, mouse model, Th1 cytokines, pulmonary surfactant, lung function, host genetics, age, cell tropism, vaccine evaluation, antiviral drug evaluation, aged mice
- MeSH terms
- Betacoronavirus, COVID-19, SARS-CoV-2, Animals, Cell Line, Disease Models, Animal, Female, Humans, Lung, Mice, Inbred BALB C, Mice, Inbred C57BL, Pneumonia, Viral, Respiratory Distress Syndrome, Severity of Illness Index, Survival Rate, Cytokines, Coronavirus Infections, Chemokines, Mice, Acute Lung Injury, Pandemics
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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