Publikationsdatenbank

Key benefits of dexamethasone and antibody treatment in COVID-19 hamster models revealed by single-cell transcriptomics (2022)

Art

Zeitschriftenartikel / wissenschaftlicher Beitrag

Autoren

Wyler, Emanuel

Adler, Julia M. (WE 5)

Eschke, Kathrin (WE 5)

Alves, G. Teixeira

Peidli, Stefan

Pott, Fabian

Kazmierski, Julia

Michalick, Laura

Kershaw, Olivia (WE 12)

Bushe, Judith (WE 12)

Andreotti, Sandro

Pennitz, Peter

Abdelgawad, Azza (WE 5)

Postmus, Dylan

Goffinet, Christine

Kreye, Jakob

Reincke, S. Momsen

Prüss, Harald

Blüthgen, Nils

Gruber, Achim D. (WE 12)

Kuebler, Wolfgang M.

Witzenrath, Martin

Landthaler, Markus

Nouailles, Geraldine

Trimpert, Jakob (WE 5)

Quelle

Molecular therapy : the journal of the American Society of Gene Therapy

Bandzählung: 30

Heftzählung: 5

Seiten: 1952 – 1965

ISSN: 1525-0016

Sprache

Englisch

Verweise

URL (Volltext): https://www.sciencedirect.com/science/article/pii/S1525001622001733

DOI: 10.1016/j.ymthe.2022.03.014

Pubmed: 35339689

Kontakt

Institut für Tierpathologie

Robert-von-Ostertag-Str. 15
14163 Berlin
+49 30 838 62450
pathologie@vetmed.fu-berlin.de

Abstract / Zusammenfassung

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.