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Key benefits of dexamethasone and antibody treatment in COVID-19 hamster models revealed by single-cell transcriptomics.
Wyler, Emanuel; Adler, Julia M; Eschke, Kathrin; Teixeira Alves, G; Peidli, Stefan; Pott, Fabian; Kazmierski, Julia; Michalick, Laura; Kershaw, Olivia; Bushe, Judith; Andreotti, Sandro; Pennitz, Peter; Abdelgawad, Azza; Postmus, Dylan; Goffinet, Christine; Kreye, Jakob; Reincke, S Momsen; Prüss, Harald; Blüthgen, Nils; Gruber, Achim D; Kuebler, Wolfgang M; Witzenrath, Martin; Landthaler, Markus; Nouailles, Geraldine; Trimpert, Jakob.
  • Wyler E; Berlin Institute for Medical Systems Biology (BIMSB), Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany. Electronic address: emanuel.wyler@mdc-berlin.de.
  • Adler JM; Institute of Virology, Freie Universität Berlin, Berlin, Germany; Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Division of Pulmonary Inflammation, Berlin, Germany.
  • Eschke K; Institute of Virology, Freie Universität Berlin, Berlin, Germany.
  • Teixeira Alves G; Berlin Institute for Medical Systems Biology (BIMSB), Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany.
  • Peidli S; Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Pathology, Berlin, Germany; IRI Life Sciences, Institute for Biology, Humboldt-Universität zu Berlin, Berlin, Germany.
  • Pott F; Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Virology, Berlin, Germany; 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; Berlin Institute of Health (BIH), Berlin, Germany.
  • Michalick L; Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Physiology, Berlin, Germany.
  • Kershaw O; Institute of Veterinary Pathology, Freie Universität Berlin, Berlin, Germany.
  • Bushe J; Institute of Veterinary Pathology, Freie Universität Berlin, Berlin, Germany.
  • Andreotti S; Bioinformatics Solution Center, Freie Universität Berlin, Berlin, Germany.
  • Pennitz P; Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Division of Pulmonary Inflammation, Berlin, Germany; Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Departmen
  • Abdelgawad A; Institute of Virology, Freie Universität Berlin, Berlin, Germany.
  • Postmus D; Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Virology, Berlin, Germany; Berlin Institute of Health (BIH), Berlin, Germany.
  • Goffinet C; Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Virology, Berlin, Germany; Berlin Institute of Health (BIH), Berlin, Germany.
  • Kreye J; German Center for Neurodegenerative Diseases (DZNE) Berlin, Helmholtz Innovation Lab BaoBab (Brain Antibody-Omics and B-Cell Lab), Berlin, Germany; Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Neurology and Exper
  • Reincke SM; German Center for Neurodegenerative Diseases (DZNE) Berlin, Helmholtz Innovation Lab BaoBab (Brain Antibody-Omics and B-Cell Lab), Berlin, Germany; Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Neurology and Exper
  • Prüss H; German Center for Neurodegenerative Diseases (DZNE) Berlin, Helmholtz Innovation Lab BaoBab (Brain Antibody-Omics and B-Cell Lab), Berlin, Germany; Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Neurology and Exper
  • Blüthgen N; Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Pathology, Berlin, Germany; IRI Life Sciences, Institute for Biology, Humboldt-Universität zu Berlin, Berlin, Germany.
  • Gruber AD; Institute of Veterinary Pathology, Freie Universität Berlin, Berlin, Germany.
  • Kuebler WM; Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Physiology, Berlin, Germany.
  • Witzenrath M; Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Division of Pulmonary Inflammation, Berlin, Germany; Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Departmen
  • Landthaler M; Berlin Institute for Medical Systems Biology (BIMSB), Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany; IRI Life Sciences, Institute for Biology, Humboldt-Universität zu Berlin, Berlin, Germany.
  • Nouailles G; Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Division of Pulmonary Inflammation, Berlin, Germany. Electronic address: geraldine.nouailles@charite.de.
  • Trimpert J; Institute of Virology, Freie Universität Berlin, Berlin, Germany. Electronic address: trimpert.jakob@fu-berlin.de.
Mol Ther ; 30(5): 1952-1965, 2022 May 04.
Article in English | MEDLINE | ID: covidwho-1783847
ABSTRACT
For coronavirus disease 2019 (COVID-19), effective and well-understood treatment options are still scarce. Since vaccine efficacy is challenged by novel variants, short-lasting immunity, and vaccine hesitancy, understanding and optimizing therapeutic options remains essential. We aimed at better understanding the effects of two standard-of-care drugs, dexamethasone and anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies, on infection and host responses. By using two COVID-19 hamster models, pulmonary immune responses were analyzed to characterize effects of single or combinatorial treatments. Pulmonary viral burden was reduced by anti-SARS-CoV-2 antibody treatment and unaltered or increased by dexamethasone alone. Dexamethasone exhibited strong anti-inflammatory effects and prevented fulminant disease in a severe disease model. Combination therapy showed additive benefits with both anti-viral and anti-inflammatory potency. Bulk and single-cell transcriptomic analyses confirmed dampened inflammatory cell recruitment into lungs upon dexamethasone treatment and identified a specifically responsive subpopulation of neutrophils, thereby indicating a potential mechanism of action. Our analyses confirm the anti-inflammatory properties of dexamethasone and suggest possible mechanisms, validate anti-viral effects of anti-SARS-CoV-2 antibody treatment, and reveal synergistic effects of a combination therapy, thus informing more effective COVID-19 therapies.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: COVID-19 Topics: Vaccines / Variants Limits: Animals Language: English Journal: Mol Ther Journal subject: Molecular Biology / Therapeutics Year: 2022 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Main subject: COVID-19 Topics: Vaccines / Variants Limits: Animals Language: English Journal: Mol Ther Journal subject: Molecular Biology / Therapeutics Year: 2022 Document Type: Article