Dexamethasone attenuates interferon-related cytokine hyperresponsiveness in COVID-19 patients

Background Dexamethasone improves the survival of COVID-19 patients in need supplemental oxygen therapy. Although its broad immunosuppressive effects are well-described, immunological mechanisms modulated by dexamethasone hospitalized with remain to be elucidated. Objective We combined functional assays and an omics-based approach investigate vitro vivo plasma peripheral blood mononuclear cells (PBMCs) patients. Methods Hospitalized eligible for therapy were recruited from general care ward between February July, 2021. Whole transcriptomic targeted proteomic analyses performed before after starting treatment. PBMCs isolated healthy individuals stimulated inactivated SARS-CoV-2 ex presence or absence transcriptome cytokine responses assessed. Results efficiently inhibited SARS-CoV-2-induced expression chemokines cytokines at transcriptional protein level. treatment resulted down-regulation genes related type I II interferon (IFN) signaling whole immune cells. In addition, attenuated circulating concentrations secreted interferon-stimulating gene 15 (ISG15) pro-inflammatory correlating disease severity lethal outcomes, such as tumor necrosis factor (TNF), interleukin-6 (IL-6), chemokine ligand 2 (CCL2), C-X-C motif 8 (CXCL8), 10 (CXCL10). that multiple pathogens Toll-like receptor (TLR) ligands, responses. Conclusion describe anti-inflammatory impact on pathways contributing hyperresponsiveness observed severe manifestations COVID-19, including I/II IFN signaling. could have adverse mild symptoms inhibiting early stages disease, whereas it exhibits beneficial clinical phenotypes diminishing hyperresponsiveness.