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A C57BL/6 Mouse Model of SARS-CoV-2 Infection Recapitulates Age- and Sex-Based Differences in Human COVID-19 Disease and Recovery.
Davis, Michael A; Voss, Kathleen; Turnbull, J Bryan; Gustin, Andrew T; Knoll, Megan; Muruato, Antonio; Hsiang, Tien-Ying; Dinnon Iii, Kenneth H; Leist, Sarah R; Nickel, Katie; Baric, Ralph S; Ladiges, Warren; Akilesh, Shreeram; Smith, Kelly D; Gale, Michael.
  • Davis MA; Center for Innate Immunity and Immune Disease, Department of Immunology, University of Washington, Seattle, WA 98109, USA.
  • Voss K; Center for Innate Immunity and Immune Disease, Department of Immunology, University of Washington, Seattle, WA 98109, USA.
  • Turnbull JB; Center for Innate Immunity and Immune Disease, Department of Immunology, University of Washington, Seattle, WA 98109, USA.
  • Gustin AT; Center for Innate Immunity and Immune Disease, Department of Immunology, University of Washington, Seattle, WA 98109, USA.
  • Knoll M; Center for Innate Immunity and Immune Disease, Department of Immunology, University of Washington, Seattle, WA 98109, USA.
  • Muruato A; Center for Innate Immunity and Immune Disease, Department of Immunology, University of Washington, Seattle, WA 98109, USA.
  • Hsiang TY; Center for Innate Immunity and Immune Disease, Department of Immunology, University of Washington, Seattle, WA 98109, USA.
  • Dinnon Iii KH; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA.
  • Leist SR; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA.
  • Nickel K; Department of Pathology, University of Washington, Seattle, WA 98195, USA.
  • Baric RS; Comparative Medicine, University of Washington, Seattle, WA 98195, USA.
  • Ladiges W; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA.
  • Akilesh S; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA.
  • Smith KD; Rapidly Emerging Antiviral Drug Discovery Initiative, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA.
  • Gale M; Department of Pathology, University of Washington, Seattle, WA 98195, USA.
Vaccines (Basel) ; 11(1)2022 Dec 25.
Article in English | MEDLINE | ID: covidwho-2229316
ABSTRACT
We present a comprehensive analysis of SARS-CoV-2 infection and recovery using wild type C57BL/6 mice and a mouse-adapted virus, and we demonstrate that this is an ideal model of infection and recovery that phenocopies acute human disease arising from the ancestral SARS-CoV-2. Disease severity and infection kinetics are age- and sex-dependent, as has been reported for humans, with older mice and males in particular exhibiting decreased viral clearance and increased mortality. We identified key parallels with human pathology, including intense virus positivity in bronchial epithelial cells, wide-spread alveolar involvement, recruitment of immune cells to the infected lungs, and acute bronchial epithelial cell death. Moreover, older animals experienced increased virus persistence, delayed dispersal of immune cells into lung parenchyma, and morphologic evidence of tissue damage and inflammation. Parallel analysis of SCID mice revealed that the adaptive immune response was not required for recovery from COVID disease symptoms nor early phase clearance of virus but was required for efficient clearance of virus at later stages of infection. Finally, transcriptional analyses indicated that induction and duration of key innate immune gene programs may explain differences in age-dependent disease severity. Importantly, these data demonstrate that SARS-CoV-2-mediated disease in C57BL/6 mice phenocopies human disease across ages and establishes a platform for future therapeutic and genetic screens for not just SARS-CoV-2 but also novel coronaviruses that have yet to emerge.
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Full text: Available Collection: International databases Database: MEDLINE Type of study: Prognostic study Topics: Long Covid Language: English Year: 2022 Document Type: Article Affiliation country: Vaccines11010047

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Full text: Available Collection: International databases Database: MEDLINE Type of study: Prognostic study Topics: Long Covid Language: English Year: 2022 Document Type: Article Affiliation country: Vaccines11010047