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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: |
Wyler, E.  ORCID: https://orcid.org/0000-0002-9884-1806, Adler, J.M., Eschke, K., Teixeira Alves, G. ORCID: https://orcid.org/0000-0002-5822-4168, Peidli, S. ORCID: https://orcid.org/0000-0002-4257-8690, 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. ORCID: https://orcid.org/0000-0002-8132-3527, Prüss, H., Blüthgen, N. ORCID: https://orcid.org/0000-0002-0171-7447, Gruber, A.D., Kuebler, W.M., Witzenrath, M., Landthaler, M. ORCID: https://orcid.org/0000-0002-1075-8734, Nouailles, G. and Trimpert, J. ORCID: https://orcid.org/0000-0003-1616-0810
|
| 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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