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.
Keywords: COVID-19 treatment; SARS-CoV-2; antibody; dexamethasone; hamster; monoclonal antibody therapy; scRNA-seq; transcriptomics.
【저자키워드】 Dexamethasone, SARS-CoV-2, antibody, monoclonal antibody therapy, COVID-19 treatment, hamster, scRNA-seq, transcriptomics., 【초록키워드】 COVID-19, Dexamethasone, Treatment, coronavirus disease, Neutrophils, antibodies, Coronavirus disease 2019, Efficacy, Vaccine, coronavirus, therapy, Immunity, Anti-inflammatory, antibody, monoclonal antibody, transcriptomics, vaccine efficacy, Infection, drugs, lung, combination therapy, pulmonary, Vaccine hesitancy, variants, monoclonal antibody therapy, Anti-viral, COVID-19 treatment, Viral, anti-SARS-CoV-2 antibody, immune responses, Lungs, mechanisms, hamster, respiratory, recruitment, disease, scRNA-seq, single-cell, Therapies, therapeutic options, Inflammatory, severe disease, host responses, therapeutic option, inflammatory cell, acute respiratory syndrome, synergistic effects, acute respiratory syndrome coronavirus, potential mechanism, anti-inflammatory properties, viral burden, anti-inflammatory effect, subpopulation, pulmonary immune response, Standard-of-care, Effect, transcriptomic, anti-viral effects, effective, benefit, Cell, synergistic, analyzed, exhibited, analysis, prevented, was reduced, anti-inflammatory property, anti-viral effect, 【제목키워드】 COVID-19, Dexamethasone, single-cell, antibody treatment, benefit,