Dexamethasone Modulates the Cytokine Response but Not COVID-19-Induced Coagulopathy in Critically Ill

Mélanie Dechamps; Julien De Poortere; Marie Octave; Audrey Ginion; Valentine Robaux; Laurence Pirotton; Julie Bodart; Damien Gruson; Marie-Astrid Van Dievoet; Jonathan Douxfils; Hélène Haguet; Laure Morimont; Marc Derive; Lucie Jolly; Luc Bertrand; Pierre-François Laterre; Sandrine Horman; Christophe Beauloye

doi:10.3390/ijms24087278

Dexamethasone Modulates the Cytokine Response but Not COVID-19-Induced Coagulopathy in Critically Ill

Mélanie Dechamps, Julien De Poortere, Marie Octave, Audrey Ginion, Valentine Robaux, Laurence Pirotton, Julie Bodart, Damien Gruson, Marie-Astrid Van Dievoet, Jonathan Douxfils, Hélène Haguet, Laure Morimont, Marc Derive, Lucie Jolly, Luc Bertrand, Pierre-François Laterre, Sandrine Horman, Christophe Beauloye

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Abstract

Severe forms of coronavirus 2019 (COVID-19) disease are caused by an exaggerated systemic inflammatory response and subsequent inflammation-related coagulopathy. Anti-inflammatory treatment with low dose dexamethasone has been shown to reduce mortality in COVID-19 patients requiring oxygen therapy. However, the mechanisms of action of corticosteroids have not been extensively studied in critically ill patients in the context of COVID-19. Plasma biomarkers of inflammatory and immune responses, endothelial and platelet activation, neutrophil extracellular trap formation, and coagulopathy were compared between patients treated or not by systemic dexamethasone for severe forms of COVID-19. Dexamethasone treatment significantly reduced the inflammatory and lymphoid immune response in critical COVID-19 patients but had little effect on the myeloid immune response and no effect on endothelial activation, platelet activation, neutrophil extracellular trap formation, and coagulopathy. The benefits of low dose dexamethasone on outcome in critical COVID-19 can be partially explained by a modulation of the inflammatory response but not by reduction of coagulopathy. Future studies should explore the impact of combining dexamethasone with other immunomodulatory or anticoagulant drugs in severe COVID-19.

Original language	English
Article number	7278
Journal	International Journal of Molecular Sciences
Volume	24
Issue number	8
DOIs	https://doi.org/10.3390/ijms24087278
Publication status	Published - 14 Apr 2023

Keywords

Humans
Cytokines
SARS-CoV-2
Critical Illness
COVID-19 Drug Treatment
COVID-19/complications
Dexamethasone/pharmacology
COVID-19
low dose dexamethasone
cytokine storm
inflammation
coagulopathy

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.3390/ijms24087278

14959-2023-Dechamps

Cite this

Dechamps, M., De Poortere, J., Octave, M., Ginion, A., Robaux, V., Pirotton, L., Bodart, J., Gruson, D., Van Dievoet, M.-A., Douxfils, J., Haguet, H., Morimont, L., Derive, M., Jolly, L., Bertrand, L., Laterre, P.-F., Horman, S., & Beauloye, C. (2023). Dexamethasone Modulates the Cytokine Response but Not COVID-19-Induced Coagulopathy in Critically Ill. International Journal of Molecular Sciences, 24(8), Article 7278. https://doi.org/10.3390/ijms24087278

@article{af9342ce05154af6858c5e8f13ad1cc6,

title = "Dexamethasone Modulates the Cytokine Response but Not COVID-19-Induced Coagulopathy in Critically Ill",

abstract = "Severe forms of coronavirus 2019 (COVID-19) disease are caused by an exaggerated systemic inflammatory response and subsequent inflammation-related coagulopathy. Anti-inflammatory treatment with low dose dexamethasone has been shown to reduce mortality in COVID-19 patients requiring oxygen therapy. However, the mechanisms of action of corticosteroids have not been extensively studied in critically ill patients in the context of COVID-19. Plasma biomarkers of inflammatory and immune responses, endothelial and platelet activation, neutrophil extracellular trap formation, and coagulopathy were compared between patients treated or not by systemic dexamethasone for severe forms of COVID-19. Dexamethasone treatment significantly reduced the inflammatory and lymphoid immune response in critical COVID-19 patients but had little effect on the myeloid immune response and no effect on endothelial activation, platelet activation, neutrophil extracellular trap formation, and coagulopathy. The benefits of low dose dexamethasone on outcome in critical COVID-19 can be partially explained by a modulation of the inflammatory response but not by reduction of coagulopathy. Future studies should explore the impact of combining dexamethasone with other immunomodulatory or anticoagulant drugs in severe COVID-19.",

keywords = "Humans, Cytokines, SARS-CoV-2, Critical Illness, COVID-19 Drug Treatment, COVID-19/complications, Dexamethasone/pharmacology, COVID-19, low dose dexamethasone, cytokine storm, inflammation, coagulopathy",

author = "M{\'e}lanie Dechamps and {De Poortere}, Julien and Marie Octave and Audrey Ginion and Valentine Robaux and Laurence Pirotton and Julie Bodart and Damien Gruson and {Van Dievoet}, Marie-Astrid and Jonathan Douxfils and H{\'e}l{\`e}ne Haguet and Laure Morimont and Marc Derive and Lucie Jolly and Luc Bertrand and Pierre-Fran{\c c}ois Laterre and Sandrine Horman and Christophe Beauloye",

note = "Funding Information: The study was supported by a grant from the “Fondation Saint-Luc” (Brussels, Belgium). The funders had no role in study design, data collection and analysis, interpretation, or writing of the manuscript. Funding Information: This work was supported by grants from the Foundation Saint-Luc (Brussels, Belgium). The Division of Cardiology at Cliniques Universitaires Saint-Luc, Belgium, has received unrestricted research grants from AstraZeneca (Belgium). MD is Clinical Master Specialist Applicant to a Ph.D. at the Fonds National de la Recherche Scientifique et M{\'e}dicale (FNRS, Belgium). JDP was supported by a grant from the Salus Sanguinis Foundation (UCLouvain, Belgium). MO, LP, and JB are supported by Fund for Research Training in Industry and Agriculture (FRIA, FNRS). LB and SH are senior research associates at FNRS. QUALIblood s.a. offered the analyses for determining the cytokine profile. Publisher Copyright: {\textcopyright} 2023 by the authors.",

year = "2023",

month = apr,

day = "14",

doi = "10.3390/ijms24087278",

language = "English",

volume = "24",

journal = "International Journal of Molecular Sciences",

issn = "1661-6596",

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Dechamps, M, De Poortere, J, Octave, M, Ginion, A, Robaux, V, Pirotton, L, Bodart, J, Gruson, D, Van Dievoet, M-A, Douxfils, J , Haguet, H , Morimont, L, Derive, M, Jolly, L, Bertrand, L, Laterre, P-F, Horman, S & Beauloye, C 2023, 'Dexamethasone Modulates the Cytokine Response but Not COVID-19-Induced Coagulopathy in Critically Ill', International Journal of Molecular Sciences, vol. 24, no. 8, 7278. https://doi.org/10.3390/ijms24087278

TY - JOUR

T1 - Dexamethasone Modulates the Cytokine Response but Not COVID-19-Induced Coagulopathy in Critically Ill

AU - Dechamps, Mélanie

AU - De Poortere, Julien

AU - Octave, Marie

AU - Ginion, Audrey

AU - Robaux, Valentine

AU - Pirotton, Laurence

AU - Bodart, Julie

AU - Gruson, Damien

AU - Van Dievoet, Marie-Astrid

AU - Douxfils, Jonathan

AU - Haguet, Hélène

AU - Morimont, Laure

AU - Derive, Marc

AU - Jolly, Lucie

AU - Bertrand, Luc

AU - Laterre, Pierre-François

AU - Horman, Sandrine

AU - Beauloye, Christophe

N1 - Funding Information: The study was supported by a grant from the “Fondation Saint-Luc” (Brussels, Belgium). The funders had no role in study design, data collection and analysis, interpretation, or writing of the manuscript. Funding Information: This work was supported by grants from the Foundation Saint-Luc (Brussels, Belgium). The Division of Cardiology at Cliniques Universitaires Saint-Luc, Belgium, has received unrestricted research grants from AstraZeneca (Belgium). MD is Clinical Master Specialist Applicant to a Ph.D. at the Fonds National de la Recherche Scientifique et Médicale (FNRS, Belgium). JDP was supported by a grant from the Salus Sanguinis Foundation (UCLouvain, Belgium). MO, LP, and JB are supported by Fund for Research Training in Industry and Agriculture (FRIA, FNRS). LB and SH are senior research associates at FNRS. QUALIblood s.a. offered the analyses for determining the cytokine profile. Publisher Copyright: © 2023 by the authors.

PY - 2023/4/14

Y1 - 2023/4/14

N2 - Severe forms of coronavirus 2019 (COVID-19) disease are caused by an exaggerated systemic inflammatory response and subsequent inflammation-related coagulopathy. Anti-inflammatory treatment with low dose dexamethasone has been shown to reduce mortality in COVID-19 patients requiring oxygen therapy. However, the mechanisms of action of corticosteroids have not been extensively studied in critically ill patients in the context of COVID-19. Plasma biomarkers of inflammatory and immune responses, endothelial and platelet activation, neutrophil extracellular trap formation, and coagulopathy were compared between patients treated or not by systemic dexamethasone for severe forms of COVID-19. Dexamethasone treatment significantly reduced the inflammatory and lymphoid immune response in critical COVID-19 patients but had little effect on the myeloid immune response and no effect on endothelial activation, platelet activation, neutrophil extracellular trap formation, and coagulopathy. The benefits of low dose dexamethasone on outcome in critical COVID-19 can be partially explained by a modulation of the inflammatory response but not by reduction of coagulopathy. Future studies should explore the impact of combining dexamethasone with other immunomodulatory or anticoagulant drugs in severe COVID-19.

AB - Severe forms of coronavirus 2019 (COVID-19) disease are caused by an exaggerated systemic inflammatory response and subsequent inflammation-related coagulopathy. Anti-inflammatory treatment with low dose dexamethasone has been shown to reduce mortality in COVID-19 patients requiring oxygen therapy. However, the mechanisms of action of corticosteroids have not been extensively studied in critically ill patients in the context of COVID-19. Plasma biomarkers of inflammatory and immune responses, endothelial and platelet activation, neutrophil extracellular trap formation, and coagulopathy were compared between patients treated or not by systemic dexamethasone for severe forms of COVID-19. Dexamethasone treatment significantly reduced the inflammatory and lymphoid immune response in critical COVID-19 patients but had little effect on the myeloid immune response and no effect on endothelial activation, platelet activation, neutrophil extracellular trap formation, and coagulopathy. The benefits of low dose dexamethasone on outcome in critical COVID-19 can be partially explained by a modulation of the inflammatory response but not by reduction of coagulopathy. Future studies should explore the impact of combining dexamethasone with other immunomodulatory or anticoagulant drugs in severe COVID-19.

KW - Humans

KW - Cytokines

KW - SARS-CoV-2

KW - Critical Illness

KW - COVID-19 Drug Treatment

KW - COVID-19/complications

KW - Dexamethasone/pharmacology

KW - COVID-19

KW - low dose dexamethasone

KW - cytokine storm

KW - inflammation

KW - coagulopathy

UR - http://www.scopus.com/inward/record.url?scp=85156194201&partnerID=8YFLogxK

U2 - 10.3390/ijms24087278

DO - 10.3390/ijms24087278

M3 - Article

C2 - 37108440

SN - 1661-6596

VL - 24

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

IS - 8

M1 - 7278

ER -

Dexamethasone Modulates the Cytokine Response but Not COVID-19-Induced Coagulopathy in Critically Ill

Abstract

Keywords

UN SDGs

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Clinical Pharmacology Research Group

The COVILAB project : Clinical laboratory investigations related to COVID-19

Catholic University of Louvain (UCLouvain) Researcher Describes Recent Advances in COVID-19 (Dexamethasone Modulates the Cytokine Response but Not COVID-19-Induced Coagulopathy in Critically Ill)

Cite this

Dexamethasone Modulates the Cytokine Response but Not COVID-19-Induced Coagulopathy in Critically Ill

Abstract

Keywords

UN SDGs

Access to Document

Other files and links

Fingerprint

Projects

Clinical Pharmacology Research Group

The COVILAB project : Clinical laboratory investigations related to COVID-19

Press/Media

Catholic University of Louvain (UCLouvain) Researcher Describes Recent Advances in COVID-19 (Dexamethasone Modulates the Cytokine Response but Not COVID-19-Induced Coagulopathy in Critically Ill)

Cite this