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@ARTICLE{Knoll:271285,
      author       = {Knoll, Rainer and Helbig, Elisa T and Dahm, Kilian and
                      Bolaji, Olufemi and Hamm, Frederik and Dietrich, Oliver and
                      van Uelft, Martina and Müller, Sophie and Bonaguro, Lorenzo
                      and Schulte-Schrepping, Jonas and Petrov, Lev and Krämer,
                      Benjamin and Kraut, Michael and Stubbemann, Paula and
                      Thibeault, Charlotte and Brumhard, Sophia and Theis, Heidi
                      and Hack, Gudrun and De Domenico, Elena and Nattermann,
                      Jacob and Becker, Matthias and Beyer, Marc D and Hillus,
                      David and Georg, Philipp and Loers, Constantin and
                      Tiedemann, Janina and Tober-Lau, Pinkus and Lippert, Lena
                      and Millet Pascual-Leone, Belén and Tacke, Frank and Rohde,
                      Gernot and Suttorp, Norbert and Witzenrath, Martin and
                      Saliba, Antoine-Emmanuel and Ulas, Thomas and Polansky,
                      Julia K and Sawitzki, Birgit and Sander, Leif E and
                      Schultze, Joachim L and Aschenbrenner, Anna C and Kurth,
                      Florian},
      collaboration = {Group, CAPNETZ Study and Group, Pa-COVID-19 Study},
      title        = {{T}he life-saving benefit of dexamethasone in severe
                      {COVID}-19 is linked to a reversal of monocyte
                      dysregulation.},
      journal      = {Cell},
      volume       = {187},
      number       = {16},
      issn         = {0092-8674},
      address      = {New York, NY},
      publisher    = {Elsevier},
      reportid     = {DZNE-2024-01024},
      pages        = {4318 - 4335.e20},
      year         = {2024},
      abstract     = {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.},
      keywords     = {Humans / Dexamethasone: pharmacology / Dexamethasone:
                      therapeutic use / Monocytes: metabolism / Monocytes: drug
                      effects / COVID-19 Drug Treatment / COVID-19 / SARS-CoV-2:
                      drug effects / Male / Single-Cell Analysis / Female /
                      Transcriptome / Middle Aged / Aged / Glucocorticoids:
                      therapeutic use / Glucocorticoids: pharmacology / Lung:
                      pathology / Adult / COVID-19 (Other) / companion diagnostics
                      (Other) / glucocorticoid (Other) / in vivo target
                      engagement (Other) / monocytes (Other) / single-cell
                      analysis (Other) / transcriptomics (Other) / treatment
                      response prediction (Other) / Dexamethasone (NLM Chemicals)
                      / Glucocorticoids (NLM Chemicals)},
      cin          = {AG Aschenbrenner / AG Schultze / AG Becker / AG Beyer /
                      PRECISE},
      ddc          = {610},
      cid          = {I:(DE-2719)5000082 / I:(DE-2719)1013038 /
                      I:(DE-2719)5000079 / I:(DE-2719)1013035 /
                      I:(DE-2719)1013031},
      pnm          = {354 - Disease Prevention and Healthy Aging (POF4-354) / 351
                      - Brain Function (POF4-351) / 352 - Disease Mechanisms
                      (POF4-352)},
      pid          = {G:(DE-HGF)POF4-354 / G:(DE-HGF)POF4-351 /
                      G:(DE-HGF)POF4-352},
      experiment   = {EXP:(DE-2719)PRECISE-20190321},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:38964327},
      doi          = {10.1016/j.cell.2024.06.014},
      url          = {https://pub.dzne.de/record/271285},
}