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Key benefits of dexamethasone and antibody treatment in COVID-19 hamster models revealed by single cell transcriptomics

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Item Type:Article
Title:Key benefits of dexamethasone and antibody treatment in COVID-19 hamster models revealed by single cell transcriptomics
Creators Name:Wyler, E. and Adler, J.M. and Eschke, K. and Teixeira Alves, G. and Peidli, S. and Pott, F. and Kazmierski, J. and Michalick, L. and Kershaw, O. and Bushe, J. and Andreotti, S. and Pennitz, P. and Abdelgawad, A. and Postmus, D. and Goffinet, C. and Kreye, J. and Reincke, S.M. and Prüss, H. and Blüthgen, N. and Gruber, A.D. and Kuebler, W.M. and Witzenrath, M. and Landthaler, M. and Nouailles, G. and Trimpert, J.
Abstract:For 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-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 similar 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.
Keywords:COVID-19 Treatment, Dexamethasone, Antibody, Monoclonal Antibody Therapy, scRNA Seq, Transcriptomics, SARS-CoV-2, Animals
Source:Molecular Therapy
ISSN:1525-0016
Publisher:Cell Press
Volume:30
Number:5
Page Range:1952-1965
Date:4 May 2022
Official Publication:https://doi.org/10.1016/j.ymthe.2022.03.014
PubMed:View item in PubMed

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