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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., 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., Reincke, S.M., Prüss, H., Blüthgen, N., Gruber, A.D., Kuebler, W.M., Witzenrath, M., Landthaler, M., 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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