Home > Publications Database > The life-saving benefit of dexamethasone in severe COVID-19 is linked to a reversal of monocyte dysregulation. > print

001     271285
005     20241203165112.0
024 7 _ |a 10.1016/j.cell.2024.06.014
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024 7 _ |a pmid:38964327
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024 7 _ |a 0092-8674
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024 7 _ |a 1097-4172
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037 _ _ |a DZNE-2024-01024
041 _ _ |a English
082 _ _ |a 610
100 1 _ |a Knoll, Rainer
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245 _ _ |a The life-saving benefit of dexamethasone in severe COVID-19 is linked to a reversal of monocyte dysregulation.
260 _ _ |a New York, NY
|c 2024
|b Elsevier
336 7 _ |a article
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336 7 _ |a ARTICLE
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520 _ _ |a 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.
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650 _ 7 |a COVID-19
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650 _ 7 |a companion diagnostics
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650 _ 7 |a glucocorticoid
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650 _ 7 |a in vivo target engagement
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650 _ 7 |a monocytes
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650 _ 7 |a single-cell analysis
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650 _ 7 |a transcriptomics
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650 _ 7 |a treatment response prediction
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650 _ 7 |a Dexamethasone
|0 7S5I7G3JQL
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650 _ 7 |a Glucocorticoids
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650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Dexamethasone: pharmacology
|2 MeSH
650 _ 2 |a Dexamethasone: therapeutic use
|2 MeSH
650 _ 2 |a Monocytes: metabolism
|2 MeSH
650 _ 2 |a Monocytes: drug effects
|2 MeSH
650 _ 2 |a COVID-19 Drug Treatment
|2 MeSH
650 _ 2 |a COVID-19
|2 MeSH
650 _ 2 |a SARS-CoV-2: drug effects
|2 MeSH
650 _ 2 |a Male
|2 MeSH
650 _ 2 |a Single-Cell Analysis
|2 MeSH
650 _ 2 |a Female
|2 MeSH
650 _ 2 |a Transcriptome
|2 MeSH
650 _ 2 |a Middle Aged
|2 MeSH
650 _ 2 |a Aged
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650 _ 2 |a Glucocorticoids: therapeutic use
|2 MeSH
650 _ 2 |a Glucocorticoids: pharmacology
|2 MeSH
650 _ 2 |a Lung: pathology
|2 MeSH
650 _ 2 |a Adult
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773 _ _ |a 10.1016/j.cell.2024.06.014
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