A Distinct Dexamethasone-Dependent Gene Expression Profile in the Lungs of COVID-19 Patients

Ulrik Fahnøe; Andreas Ronit; Ronan M G Berg; Sofie E Jørgensen; Trine H Mogensen; Alexander P Underwood; Troels K H Scheel; Jens Bukh; Ronni R Plovsing

doi:10.1093/infdis/jiac218

A Distinct Dexamethasone-Dependent Gene Expression Profile in the Lungs of COVID-19 Patients

J Infect Dis. 2022 Dec 13;226(12):2137-2141. doi: 10.1093/infdis/jiac218.

Authors

Ulrik Fahnøe^{1

2}, Andreas Ronit², Ronan M G Berg^{3

4

5

6}, Sofie E Jørgensen⁷, Trine H Mogensen^{7

8

9}, Alexander P Underwood^{1

2}, Troels K H Scheel^{1

2

10}, Jens Bukh^{1

2}, Ronni R Plovsing^{11

12}

Affiliations

¹ Copenhagen Hepatitis C Program, Department of Infectious Diseases, Hvidovre Hospital and Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
² Department of Infectious Diseases, Copenhagen University Hospital-Amager and Hvidovre Hospitals, Hvidovre, Denmark.
³ Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
⁴ Department of Clinical Physiology and Nuclear Medicine, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark.
⁵ Centre for Physical Activity Research, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark.
⁶ Neurovascular Research Laboratory, Faculty of Life Sciences and Education, University of South Wales, Pontypridd, United Kingdom.
⁷ Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark.
⁸ Department of Biomedicine, Aarhus Research Center for Innate Immunology, Aarhus University, Aarhus, Denmark.
⁹ Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
¹⁰ Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, New York, USA.
¹¹ Department of Anesthesiology and Intensive Care, Copenhagen University Hospital-Amager and Hvidovre Hospitals, Hvidovre, Denmark.
¹² Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

Abstract

The effects of dexamethasone (DXM) treatment on pulmonary immunity in COVID-19-associated acute respiratory distress syndrome (CARDS) remain insufficiently understood. We performed transcriptomic RNA-seq analysis of bronchoalveolar lavage fluid from 20 mechanically ventilated patients: 12 with CARDS (with or without DXM) and 8 non-COVID-19 critically ill controls. CARDS with DXM was characterized by upregulation of genes related to B-cell and complement pathway activation, antigen presentation, phagocytosis, and FC-γ receptor signaling. Most interferon-stimulated genes were upregulated in CARDS, particularly in CARDS without DXM. In conclusion, DXM treatment was not associated with regulation of proinflammatory pathways in CARDS but with regulation of other local immune responses. Clinical Trials Registration. NCT04354584.

Keywords: acute respiratory distress syndrome; bronchoalveolar lavage fluid; coronavirus disease 2019; inflammation; interferon stimulated genes; transcriptome profiling.

Publication types

Clinical Trial
Research Support, Non-U.S. Gov't

MeSH terms

Bronchoalveolar Lavage Fluid
COVID-19* / genetics
Dexamethasone / pharmacology
Dexamethasone / therapeutic use
Humans
Lung
Pneumonia*
Respiratory Distress Syndrome* / drug therapy
Transcriptome

Substances

Dexamethasone

Associated data

ClinicalTrials.gov/NCT04354584

Grants and funding

802899/ERC_/European Research Council/International