%0 Journal Article
%A Knoll, Rainer
%A Helbig, Elisa T
%A Dahm, Kilian
%A Bolaji, Olufemi
%A Hamm, Frederik
%A Dietrich, Oliver
%A van Uelft, Martina
%A Müller, Sophie
%A Bonaguro, Lorenzo
%A Schulte-Schrepping, Jonas
%A Petrov, Lev
%A Krämer, Benjamin
%A Kraut, Michael
%A Stubbemann, Paula
%A Thibeault, Charlotte
%A Brumhard, Sophia
%A Theis, Heidi
%A Hack, Gudrun
%A De Domenico, Elena
%A Nattermann, Jacob
%A Becker, Matthias
%A Beyer, Marc D
%A Hillus, David
%A Georg, Philipp
%A Loers, Constantin
%A Tiedemann, Janina
%A Tober-Lau, Pinkus
%A Lippert, Lena
%A Millet Pascual-Leone, Belén
%A Tacke, Frank
%A Rohde, Gernot
%A Suttorp, Norbert
%A Witzenrath, Martin
%A Saliba, Antoine-Emmanuel
%A Ulas, Thomas
%A Polansky, Julia K
%A Sawitzki, Birgit
%A Sander, Leif E
%A Schultze, Joachim L
%A Aschenbrenner, Anna C
%A Kurth, Florian
%T The life-saving benefit of dexamethasone in severe COVID-19 is linked to a reversal of monocyte dysregulation.
%J Cell
%V 187
%N 16
%@ 0092-8674
%C New York, NY
%I Elsevier
%M DZNE-2024-01024
%P 4318 - 4335.e20
%D 2024
%X Dexamethasone is a life-saving treatment for severe COVID-19, yet its mechanism of action is unknown, and many patients deteriorate or die despite timely treatment initiation. Here, we identify dexamethasone treatment-induced cellular and molecular changes associated with improved survival in COVID-19 patients. We observed a reversal of transcriptional hallmark signatures in monocytes associated with severe COVID-19 and the induction of a monocyte substate characterized by the expression of glucocorticoid-response genes. These molecular responses to dexamethasone were detected in circulating and pulmonary monocytes, and they were directly linked to survival. Monocyte single-cell RNA sequencing (scRNA-seq)-derived signatures were enriched in whole blood transcriptomes of patients with fatal outcome in two independent cohorts, highlighting the potential for identifying non-responders refractory to dexamethasone. Our findings link the effects of dexamethasone to specific immunomodulation and reversal of monocyte dysregulation, and they highlight the potential of single-cell omics for monitoring in vivo target engagement of immunomodulatory drugs and for patient stratification for precision medicine approaches.
%K Humans
%K Dexamethasone: pharmacology
%K Dexamethasone: therapeutic use
%K Monocytes: metabolism
%K Monocytes: drug effects
%K COVID-19 Drug Treatment
%K COVID-19
%K SARS-CoV-2: drug effects
%K Male
%K Single-Cell Analysis
%K Female
%K Transcriptome
%K Middle Aged
%K Aged
%K Glucocorticoids: therapeutic use
%K Glucocorticoids: pharmacology
%K Lung: pathology
%K Adult
%K COVID-19 (Other)
%K companion diagnostics (Other)
%K glucocorticoid (Other)
%K in vivo target engagement (Other)
%K monocytes (Other)
%K single-cell analysis (Other)
%K transcriptomics (Other)
%K treatment response prediction (Other)
%K Dexamethasone (NLM Chemicals)
%K Glucocorticoids (NLM Chemicals)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:38964327
%R 10.1016/j.cell.2024.06.014
%U https://pub.dzne.de/record/271285