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

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 antiviral 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.

Automated summary

This study investigated the effects of dexamethasone and anti-SARS-CoV-2 antibodies on COVID-19 treatment. Dexamethasone exhibited strong anti-inflammatory properties and prevented severe disease outbreaks. Anti-SARS-CoV-2 antibody treatment reduced pulmonary viral burden. Combination therapy showed additive benefits in both antiviral and anti-inflammatory effects.