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SARS-CoV-2 infection produces chronic pulmonary epithelial and immune cell dysfunction with fibrosis in mice.
Dinnon, Kenneth H; Leist, Sarah R; Okuda, Kenichi; Dang, Hong; Fritch, Ethan J; Gully, Kendra L; De la Cruz, Gabriela; Evangelista, Mia D; Asakura, Takanori; Gilmore, Rodney C; Hawkins, Padraig; Nakano, Satoko; West, Ande; Schäfer, Alexandra; Gralinski, Lisa E; Everman, Jamie L; Sajuthi, Satria P; Zweigart, Mark R; Dong, Stephanie; McBride, Jennifer; Cooley, Michelle R; Hines, Jesse B; Love, Miriya K; Groshong, Steve D; VanSchoiack, Alison; Phelan, Stefan J; Liang, Yan; Hether, Tyler; Leon, Michael; Zumwalt, Ross E; Barton, Lisa M; Duval, Eric J; Mukhopadhyay, Sanjay; Stroberg, Edana; Borczuk, Alain; Thorne, Leigh B; Sakthivel, Muthu K; Lee, Yueh Z; Hagood, James S; Mock, Jason R; Seibold, Max A; O'Neal, Wanda K; Montgomery, Stephanie A; Boucher, Richard C; Baric, Ralph S.
Afiliação
  • Dinnon KH; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
  • Leist SR; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
  • Okuda K; Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
  • Dang H; Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
  • Fritch EJ; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
  • Gully KL; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
  • De la Cruz G; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
  • Evangelista MD; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
  • Asakura T; Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
  • Gilmore RC; Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
  • Hawkins P; Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
  • Nakano S; Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
  • West A; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
  • Schäfer A; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
  • Gralinski LE; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
  • Everman JL; Center for Genes, Environment, and Health, National Jewish Health, Denver, CO 80206, USA.
  • Sajuthi SP; Center for Genes, Environment, and Health, National Jewish Health, Denver, CO 80206, USA.
  • Zweigart MR; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
  • Dong S; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
  • McBride J; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
  • Cooley MR; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
  • Hines JB; Golden Point Scientific Laboratories, Hoover, AL 35216, USA.
  • Love MK; Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
  • Groshong SD; Division of Pathology, Department of Medicine, National Jewish Health, Denver, CO 80206, USA.
  • VanSchoiack A; NanoString Technologies, Seattle, WA 98109, USA.
  • Phelan SJ; NanoString Technologies, Seattle, WA 98109, USA.
  • Liang Y; NanoString Technologies, Seattle, WA 98109, USA.
  • Hether T; NanoString Technologies, Seattle, WA 98109, USA.
  • Leon M; NanoString Technologies, Seattle, WA 98109, USA.
  • Zumwalt RE; Department of Pathology and Laboratory Medicine, Mayo Clinic, Rochester, MN 55905, USA.
  • Barton LM; Office of the Chief Medical Examiner, Oklahoma City, OK 73105, USA.
  • Duval EJ; Office of the Chief Medical Examiner, Oklahoma City, OK 73105, USA.
  • Mukhopadhyay S; Department of Pathology, Cleveland Clinic, Cleveland, OH 44195, USA.
  • Stroberg E; Office of the Chief Medical Examiner, Oklahoma City, OK 73105, USA.
  • Borczuk A; Weill Cornell Medicine, New York, NY 10065, USA.
  • Thorne LB; Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
  • Sakthivel MK; Department of Radiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
  • Lee YZ; Department of Radiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
  • Hagood JS; Biomedical Research Imaging Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
  • Mock JR; Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
  • Seibold MA; Pulmonology Division and Program for Rare and Interstitial Lung Disease, Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
  • O'Neal WK; Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
  • Montgomery SA; Division of Pulmonary Diseases and Critical Care Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
  • Boucher RC; Center for Genes, Environment, and Health, National Jewish Health, Denver, CO 80206, USA.
  • Baric RS; Department of Pediatrics, National Jewish Health, Denver, CO 80206, USA.
Sci Transl Med ; 14(664): eabo5070, 2022 09 28.
Article em En | MEDLINE | ID: mdl-35857635
A subset of individuals who recover from coronavirus disease 2019 (COVID-19) develop post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (PASC), but the mechanistic basis of PASC-associated lung abnormalities suffers from a lack of longitudinal tissue samples. The mouse-adapted SARS-CoV-2 strain MA10 produces an acute respiratory distress syndrome in mice similar to humans. To investigate PASC pathogenesis, studies of MA10-infected mice were extended from acute to clinical recovery phases. At 15 to 120 days after virus clearance, pulmonary histologic findings included subpleural lesions composed of collagen, proliferative fibroblasts, and chronic inflammation, including tertiary lymphoid structures. Longitudinal spatial transcriptional profiling identified global reparative and fibrotic pathways dysregulated in diseased regions, similar to human COVID-19. Populations of alveolar intermediate cells, coupled with focal up-regulation of profibrotic markers, were identified in persistently diseased regions. Early intervention with antiviral EIDD-2801 reduced chronic disease, and early antifibrotic agent (nintedanib) intervention modified early disease severity. This murine model provides opportunities to identify pathways associated with persistent SARS-CoV-2 pulmonary disease and test countermeasures to ameliorate PASC.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: COVID-19 Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Revista: Sci Transl Med Assunto da revista: CIENCIA / MEDICINA Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: COVID-19 Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Revista: Sci Transl Med Assunto da revista: CIENCIA / MEDICINA Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Estados Unidos