Distinct pulmonary and systemic effects of dexamethasone in severe COVID-19

Dexamethasone is the standard of care for critically ill patients with COVID-19, but its immunological effects in this setting and the mechanisms by which it decreases mortality are not understood. We performed bulk and single-cell RNA sequencing of the lower respiratory tract and blood, and plasma cytokine profiling to study the effect of dexamethasone on systemic and pulmonary immune cells. We find signatures of decreased viral injury, antigen presentation, and T cell recruitment in patients treated with dexamethasone. We identify compartment- and cell- specific differences in the effect of dexamethasone in patients with severe COVID that are reproducible in publicly available datasets. Our results highlight the importance of studying compartmentalized inflammation in critically ill patients. Overall design: Cells from whole-blood and tracheal aspirate of severely ill COVID-19 patients that were or were not treated with dexamethasone were analyzed using single-cell RNA sequencing