A unique dexamethasone-dependent gene expression profile in the lungs of COVID-19 patients

Abstract

AbstractLocal immunopathogenesis of COVID-19 acute respiratory distress syndrome (CARDS) and the effects of systemic dexamethasone (DXM) treatment on pulmonary immunity in COVID-19 remain insufficiently understood. To provide further insight into insight into immune regulatory mechanisms in the lungs of CARDS (with and without DXM treatment) and critically ill non-COVID-19 patients (without DXM treatment), transcriptomic RNA-seq analysis of bronchoalveolar lavage fluid (BALF) was performed in these patients. Functional analysis was performed using gene ontology and a blood transcription module, and gene expression of select pro-inflammatory cytokines, interferon-stimulated genes (ISGs) and auto-IFN antibodies were assessed. We found 550 and 2173 differentially expressed genes in patients with non-DXM-CARDS and DXM-CARDS, respectively. DXM-CARDS was characterized by upregulation of genes related to pulmonary innate and adaptive immunity, notably B-cell and complement pathway activation, antigen presentation, phagocytosis and FC-gamma receptor signalling. Pro-inflammatory genes were not differentially expressed in CARDS vs. non-COVID-19, nor did they differ according to DXM. Most ISGs were specifically upregulated in CARDS, particularly in non-DXM-CARDS. Auto-IFN autoantibodies were detectable in BALF of some CARDS patients. In conclusion, DXM treatment was not associated with regulation of pro-inflammatory pathways in CARDS but with regulation of other specific local innate and adaptive immune responses.summaryThis study identifies differentially expressed genes in bronchoalveolar fluid of COVID-19 acute respiratory distress patients with a distinct RNA expression profile of those treated with dexamethasone. These results challenge the concept of a COVID-19 specific cytokine storm.