The life-saving benefit of dexamethasone in severe COVID-19 is linked to a reversal of monocyte dysregulation

• DOI: 10.1016/j.cell.2024.06.014
• Publication Date: 2024-07-03T15:22:41Z
• Authors: Rainer Knoll; Elisa T. Helbig; Kilian Dahm; Olufemi Bolaji; Frederik Hamm; Oliver Dietrich; Martina van Uelft; Sophie Müller; Lorenzo Bonaguro; Jonas Schulte-Sch...; Lev Petrov; Benjamin Krämer; Michael Kraut; Paula Stubbemann; Charlotte Thibeault; Sophia Brumhard; Heidi Theis; Gudrun Hack; Elena De Domenico; Jacob Nattermann; Matthias Becker; Marc D. Beyer; David Hillus; Philipp Georg; Constantin Loers; Janina Tiedemann; Pinkus Tober-Lau; Lena Lippert; Belén Millet Pasc...; Frank Tacke; Gernot Rohde; Norbert Suttorp; Martin Witzenrath; Antoine-Emmanuel ...; Thomas Ulas; Julia K. Polansky; Birgit Sawitzki; Leif E. Sander; Joachim L. Schultze; Anna C. Aschenbre...; Florian Kurth
• Keywords: Monocyte; 2019-20 coronavirus outbreak; Pandemic

Dexamethasone is a life-saving treatment for severe COVID-19, yet its mechanism of action unknown, and many patients deteriorate or die despite timely initiation. Here, we identify dexamethasone treatment-induced cellular molecular changes associated with improved survival in COVID-19 patients. We observed reversal transcriptional hallmark signatures monocytes the induction monocyte substate characterized by expression glucocorticoid-response genes. These responses to were detected circulating pulmonary monocytes, they directly linked survival. Monocyte single-cell RNA sequencing (scRNA-seq)-derived enriched whole blood transcriptomes fatal outcome two independent cohorts, highlighting potential identifying non-responders refractory dexamethasone. Our findings link effects specific immunomodulation dysregulation, highlight omics monitoring vivo target engagement immunomodulatory drugs patient stratification precision medicine approaches.