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Temporal omics analysis in Syrian hamsters unravel cellular effector responses to moderate COVID-19.
Nouailles, Geraldine; Wyler, Emanuel; Pennitz, Peter; Postmus, Dylan; Vladimirova, Daria; Kazmierski, Julia; Pott, Fabian; Dietert, Kristina; Muelleder, Michael; Farztdinov, Vadim; Obermayer, Benedikt; Wienhold, Sandra-Maria; Andreotti, Sandro; Hoefler, Thomas; Sawitzki, Birgit; Drosten, Christian; Sander, Leif E; Suttorp, Norbert; Ralser, Markus; Beule, Dieter; Gruber, Achim D; Goffinet, Christine; Landthaler, Markus; Trimpert, Jakob; Witzenrath, Martin.
  • Nouailles G; Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Division of Pulmonary Inflammation, Berlin, Germany. geraldine.nouailles@charite.de.
  • Wyler E; Berlin Institute of Health (BIH), Berlin, Germany. geraldine.nouailles@charite.de.
  • Pennitz P; Berlin Institute for Medical Systems Biology (BIMSB), Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany. emanuel.wyler@mdc-berlin.de.
  • Postmus D; Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Division of Pulmonary Inflammation, Berlin, Germany.
  • Vladimirova D; Berlin Institute of Health (BIH), Berlin, Germany.
  • Kazmierski J; Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Virology, Berlin, Germany.
  • Pott F; Institute of Virology, Freie Universität Berlin, Berlin, Germany.
  • Dietert K; Berlin Institute of Health (BIH), Berlin, Germany.
  • Muelleder M; Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Virology, Berlin, Germany.
  • Farztdinov V; Berlin Institute of Health (BIH), Berlin, Germany.
  • Obermayer B; Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Virology, Berlin, Germany.
  • Wienhold SM; Institute of Veterinary Pathology, Freie Universität Berlin, Berlin, Germany.
  • Andreotti S; Veterinary Centre for Resistance Research, Freie Universität Berlin, Berlin, Germany.
  • Hoefler T; Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Core Facility - High-Throughput Mass Spectrometry, Berlin, Germany.
  • Sawitzki B; Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Core Facility - High-Throughput Mass Spectrometry, Berlin, Germany.
  • Drosten C; Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Core Unit Bioinformatics, Berlin, Germany.
  • Sander LE; Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Division of Pulmonary Inflammation, Berlin, Germany.
  • Suttorp N; Bioinformatics Solution Center, Freie Universität Berlin, Berlin, Germany.
  • Ralser M; Institute of Virology, Freie Universität Berlin, Berlin, Germany.
  • Beule D; Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Medical Immunology, Berlin, Germany.
  • Gruber AD; Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Virology, Berlin, Germany.
  • Goffinet C; Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Infectious Diseases and Respiratory Medicine, Berlin, Germany.
  • Landthaler M; Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Infectious Diseases and Respiratory Medicine, Berlin, Germany.
  • Trimpert J; The Francis Crick Institute, Molecular Biology of Metabolism Laboratory, London, UK.
  • Witzenrath M; Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Biochemistry, Berlin, Germany.
Nat Commun ; 12(1): 4869, 2021 08 11.
Article in English | MEDLINE | ID: covidwho-1354100
ABSTRACT
In COVID-19, immune responses are key in determining disease severity. However, cellular mechanisms at the onset of inflammatory lung injury in SARS-CoV-2 infection, particularly involving endothelial cells, remain ill-defined. Using Syrian hamsters as a model for moderate COVID-19, we conduct a detailed longitudinal analysis of systemic and pulmonary cellular responses, and corroborate it with datasets from COVID-19 patients. Monocyte-derived macrophages in lungs exert the earliest and strongest transcriptional response to infection, including induction of pro-inflammatory genes, while epithelial cells show weak alterations. Without evidence for productive infection, endothelial cells react, depending on cell subtypes, by strong and early expression of anti-viral, pro-inflammatory, and T cell recruiting genes. Recruitment of cytotoxic T cells as well as emergence of IgM antibodies precede viral clearance at day 5 post infection. Investigating SARS-CoV-2 infected Syrian hamsters thus identifies cell type-specific effector functions, providing detailed insights into pathomechanisms of COVID-19 and informing therapeutic strategies.
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Full text: Available Collection: International databases Database: MEDLINE Document Type: Article Main subject: Disease Models, Animal / COVID-19 Subject: Disease Models, Animal / COVID-19 Language: English Journal: Nat Commun Year: 2021

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Full text: Available Collection: International databases Database: MEDLINE Document Type: Article Main subject: Disease Models, Animal / COVID-19 Subject: Disease Models, Animal / COVID-19 Language: English Journal: Nat Commun Year: 2021
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