biostudies-literatureUnknown28(1)Sinha SAlthough critical for host defense, innate immune cells are also pathologic drivers of acute respiratory distress syndrome (ARDS). Innate immune dynamics during Coronavirus Disease 2019 (COVID-19) ARDS, compared to ARDS from other respiratory pathogens, is unclear. Moreover, mechanisms underlying the beneficial effects of dexamethasone during severe COVID-19 remain elusive. Using single-cell RNA sequencing and plasma proteomics, we discovered that, compared to bacterial ARDS, COVID-19 was associated with expansion of distinct neutrophil states characterized by interferon (IFN) and prostaglandin signaling. Dexamethasone during severe COVID-19 affected circulating neutrophils, altered IFN^active neutrophils, downregulated interferon-stimulated genes and activated IL-1R2⁺Nature medicine201-211https://www.ebi.ac.uk/biostudies/studies/S-EPMC8799469biostudies-literatureDexamethasone modulates immature neutrophils and interferon programming in severe COVID-19.PMC8799469Cao LYipp BGNguyen APRosin NLLabit EJaffer AArora RDufour ABromley ASinha SGillrie MRBiernaskie JFritzler MJFarias Rde Almeida LGNMcDonald BfalseDexamethasone modulates immature neutrophils and interferon programming in severe COVID-19.Although critical for host defense, innate immune cells are also pathologic drivers of acute respiratory distress syndrome (ARDS). Innate immune dynamics during Coronavirus Disease 2019 (COVID-19) ARDS, compared to ARDS from other respiratory pathogens, is unclear. Moreover, mechanisms underlying the beneficial effects of dexamethasone during severe COVID-19 remain elusive. Using single-cell RNA sequencing and plasma proteomics, we discovered that, compared to bacterial ARDS, COVID-19 was associated with expansion of distinct neutrophil states characterized by interferon (IFN) and prostaglandin signaling. Dexamethasone during severe COVID-19 affected circulating neutrophils, altered IFN^active neutrophils, downregulated interferon-stimulated genes and activated IL-1R2⁺2022-01-01T00:00:00Z2022 Jan2026-06-18T05:44:48.089Z2025-04-04T08:41:35.409ZS-EPMC87994693478279010.1038/s41591-021-01576-3