Knoll et al., Cell 2024: The life-saving benefit of dexamethasone in severe COVID-19 is linked to a reversal of monocyte dysregulation

Graphical Abstract generated with Biorender.com

Dexamethasone elicits beneficial effects in COVID-19 patients requiring respiratory support, yet many patients progress unfavorably and molecular or cellular correlates of treatment responses are not defined. Here, we identify cellular and molecular changes in immune cells in COVID-19 patients upon dexamethasone treatment, notably reversal of monocyte hallmark signatures associated with COVID-19 severity and induction of a monocyte substate expressing glucocorticoid-response genes. Responsiveness of circulating monocytes was identified as a correlate of clinical response to dexamethasone, also present in bronchoalveolar lavage fluid monocytes of dexamethasone-treated patients recovering from disease. Monocyte scRNAseq-derived signatures enriched in blood transcriptomes of patients with fatal outcome, highlighting the potential for identifying non-responders refractory to dexamethasone. Our findings link the life-saving effects of dexamethasone in COVID-19 to specific immunomodulation reversing monocyte dysregulation. The study highlights the potential of single-cell omics for monitoring in vivo target engagement of immunomodulatory drugs and for patient stratification for precision medicine approaches.

This repository contains the code and R scripts to recreate the figures of the Knoll et al. manuscript. Seurat objects for the single-cell analysis are available upon request.