Intensive care unit (ICU) admissions and mortality in severe COVID-19 patients are driven by “cytokine storms” and acute respiratory distress syndrome (ARDS). Interim clinical trial results suggest that the corticosteroid dexamethasone displays better 28-day survival in severe COVID-19 patients requiring ventilation or oxygen. In this study, 10 out of 16 patients (62.5%) that had an average plasma IL-6 value over 10 pg/mL post administration of corticosteroids also had worse outcomes (i.e., ICU stay >15 days or death), compared to 8 out of 41 patients (19.5%) who did not receive corticosteroids ( p -value = 0.0024). Given this potential association between post-corticosteroid IL-6 levels and COVID-19 severity, we hypothesized that the glucocorticoid receptor (GR or NR3C1) may be coupled to IL-6 expression in specific cell types that govern cytokine release syndrome (CRS). Examining single-cell RNA-seq data from BALF of severe COVID-19 patients and nearly 2 million cells from a pan-tissue scan shows that alveolar macrophages, smooth muscle cells, and endothelial cells co-express NR3C1 and IL-6, motivating future studies on the links between the regulation of NR3C1 function and IL-6 levels.
【저자키워드】 viral infection, Drug development, Predictive markers, 【초록키워드】 Corticosteroid, Dexamethasone, ARDS, clinical trial, Mortality, IL-6, Ventilation, COVID-19 severity, oxygen, outcome, glucocorticoid, ICU, Cytokine release syndrome, survival, single-cell RNA-seq, Patient, death, plasma, receptor, BALF, Admission, Care, association, acute respiratory distress, Endothelial cell, CRS, Alveolar macrophages, IL-6 levels, cell type, Regulation, average, syndrome, NR3C1, IL-6 expression, Cell, smooth muscle cells, driven by, receive, administration of corticosteroid, Examining, IL-6 level, Interim, severe COVID-19 patient, 【제목키워드】 ICU, Critically ill, COVID-19 patient, corticosteroid therapy, IL-6 level,