Journal Article

DZNE-2022-00488

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Key benefits of dexamethasone and antibody treatment in COVID-19 hamster models revealed by single-cell transcriptomics.

Wyler, E. ; Adler, J. M. ; Eschke, K. ; Teixeira Alves, G. ; Peidli, S. ; Pott, F. ; Kazmierski, J. ; Michalick, L. ; Kershaw, O. ; Bushe, J. ; Andreotti, S. ; Pennitz, P. ; Abdelgawad, A. ; Postmus, D. ; Goffinet, C. ; Kreye, J.DZNE* ; Reincke, S. M.DZNE* ; Prüss, H.DZNE* ; Blüthgen, N. ; Gruber, A. D. ; Kuebler, W. M. ; Witzenrath, M. ; Landthaler, M. ; Nouailles, G. ; Trimpert, J.

2022
Nature Publ. Group New York, NY

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Please use a persistent id in citations: doi:10.1016/j.ymthe.2022.03.014

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.

Keyword(s): Animals (MeSH) ; Anti-Inflammatory Agents: pharmacology (MeSH) ; Anti-Inflammatory Agents: therapeutic use (MeSH) ; Antibodies, Viral (MeSH) ; Antiviral Agents (MeSH) ; Cricetinae (MeSH) ; Dexamethasone: pharmacology (MeSH) ; SARS-CoV-2 (MeSH) ; Transcriptome (MeSH) ; COVID-19 Drug Treatment (MeSH) ; COVID-19 treatment ; SARS-CoV-2 ; antibody ; dexamethasone ; hamster ; monoclonal antibody therapy ; scRNA-seq ; transcriptomics

Note: (CC BY)

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Contributing Institute(s):

1. Autoimmune Enzephalopathies (AG Prüß)

Research Program(s):

1. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)

Appears in the scientific report 2022

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Database coverage:
; ; ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 10 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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