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000271285 0247_ $$2doi$$a10.1016/j.cell.2024.06.014
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000271285 1001_ $$0P:(DE-2719)9000620$$aKnoll, Rainer$$b0$$eFirst author$$udzne
000271285 245__ $$aThe life-saving benefit of dexamethasone in severe COVID-19 is linked to a reversal of monocyte dysregulation.
000271285 260__ $$aNew York, NY$$bElsevier$$c2024
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000271285 520__ $$aDexamethasone 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.
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000271285 650_7 $$2Other$$aCOVID-19
000271285 650_7 $$2Other$$acompanion diagnostics
000271285 650_7 $$2Other$$aglucocorticoid
000271285 650_7 $$2Other$$ain vivo target engagement
000271285 650_7 $$2Other$$amonocytes
000271285 650_7 $$2Other$$asingle-cell analysis
000271285 650_7 $$2Other$$atranscriptomics
000271285 650_7 $$2Other$$atreatment response prediction
000271285 650_7 $$07S5I7G3JQL$$2NLM Chemicals$$aDexamethasone
000271285 650_7 $$2NLM Chemicals$$aGlucocorticoids
000271285 650_2 $$2MeSH$$aHumans
000271285 650_2 $$2MeSH$$aDexamethasone: pharmacology
000271285 650_2 $$2MeSH$$aDexamethasone: therapeutic use
000271285 650_2 $$2MeSH$$aMonocytes: metabolism
000271285 650_2 $$2MeSH$$aMonocytes: drug effects
000271285 650_2 $$2MeSH$$aCOVID-19 Drug Treatment
000271285 650_2 $$2MeSH$$aCOVID-19
000271285 650_2 $$2MeSH$$aSARS-CoV-2: drug effects
000271285 650_2 $$2MeSH$$aMale
000271285 650_2 $$2MeSH$$aSingle-Cell Analysis
000271285 650_2 $$2MeSH$$aFemale
000271285 650_2 $$2MeSH$$aTranscriptome
000271285 650_2 $$2MeSH$$aMiddle Aged
000271285 650_2 $$2MeSH$$aAged
000271285 650_2 $$2MeSH$$aGlucocorticoids: therapeutic use
000271285 650_2 $$2MeSH$$aGlucocorticoids: pharmacology
000271285 650_2 $$2MeSH$$aLung: pathology
000271285 650_2 $$2MeSH$$aAdult
000271285 693__ $$0EXP:(DE-2719)PRECISE-20190321$$5EXP:(DE-2719)PRECISE-20190321$$ePlatform for Single Cell Genomics and Epigenomics at DZNE  University of Bonn$$x0
000271285 7001_ $$aHelbig, Elisa T$$b1
000271285 7001_ $$0P:(DE-2719)9001875$$aDahm, Kilian$$b2$$udzne
000271285 7001_ $$aBolaji, Olufemi$$b3
000271285 7001_ $$aHamm, Frederik$$b4
000271285 7001_ $$aDietrich, Oliver$$b5
000271285 7001_ $$0P:(DE-2719)9002579$$avan Uelft, Martina$$b6$$udzne
000271285 7001_ $$0P:(DE-2719)9001774$$aMüller, Sophie$$b7$$udzne
000271285 7001_ $$0P:(DE-2719)9001512$$aBonaguro, Lorenzo$$b8$$udzne
000271285 7001_ $$0P:(DE-2719)9001500$$aSchulte-Schrepping, Jonas$$b9$$udzne
000271285 7001_ $$aPetrov, Lev$$b10
000271285 7001_ $$aKrämer, Benjamin$$b11
000271285 7001_ $$0P:(DE-2719)9000840$$aKraut, Michael$$b12$$udzne
000271285 7001_ $$aStubbemann, Paula$$b13
000271285 7001_ $$aThibeault, Charlotte$$b14
000271285 7001_ $$aBrumhard, Sophia$$b15
000271285 7001_ $$0P:(DE-2719)2812165$$aTheis, Heidi$$b16$$udzne
000271285 7001_ $$aHack, Gudrun$$b17
000271285 7001_ $$0P:(DE-2719)9000846$$aDe Domenico, Elena$$b18$$udzne
000271285 7001_ $$aNattermann, Jacob$$b19
000271285 7001_ $$0P:(DE-2719)2812750$$aBecker, Matthias$$b20$$udzne
000271285 7001_ $$0P:(DE-2719)2812219$$aBeyer, Marc D$$b21$$udzne
000271285 7001_ $$aHillus, David$$b22
000271285 7001_ $$aGeorg, Philipp$$b23
000271285 7001_ $$aLoers, Constantin$$b24
000271285 7001_ $$aTiedemann, Janina$$b25
000271285 7001_ $$aTober-Lau, Pinkus$$b26
000271285 7001_ $$aLippert, Lena$$b27
000271285 7001_ $$aMillet Pascual-Leone, Belén$$b28
000271285 7001_ $$aTacke, Frank$$b29
000271285 7001_ $$aRohde, Gernot$$b30
000271285 7001_ $$aSuttorp, Norbert$$b31
000271285 7001_ $$aWitzenrath, Martin$$b32
000271285 7001_ $$aGroup, CAPNETZ Study$$b33$$eCollaboration Author
000271285 7001_ $$aGroup, Pa-COVID-19 Study$$b34$$eCollaboration Author
000271285 7001_ $$aSaliba, Antoine-Emmanuel$$b35
000271285 7001_ $$0P:(DE-2719)9000845$$aUlas, Thomas$$b36$$udzne
000271285 7001_ $$aPolansky, Julia K$$b37
000271285 7001_ $$aSawitzki, Birgit$$b38
000271285 7001_ $$aSander, Leif E$$b39
000271285 7001_ $$0P:(DE-2719)2811660$$aSchultze, Joachim L$$b40$$udzne
000271285 7001_ $$0P:(DE-2719)2812913$$aAschenbrenner, Anna C$$b41$$udzne
000271285 7001_ $$aKurth, Florian$$b42
000271285 773__ $$0PERI:(DE-600)2001951-8$$a10.1016/j.cell.2024.06.014$$gVol. 187, no. 16, p. 4318 - 4335.e20$$n16$$p4318 - 4335.e20$$tCell$$v187$$x0092-8674$$y2024
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