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. 2023 Apr 14;24(8):7278.
doi: 10.3390/ijms24087278.

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

Mélanie Dechamps  1   2 , Julien De Poortere  1 , Marie Octave  1 , Audrey Ginion  1 , Valentine Robaux  1 , Laurence Pirotton  1 , Julie Bodart  1 , Damien Gruson  3 , Marie-Astrid Van Dievoet  3 , Jonathan Douxfils  4   5 , Hélène Haguet  4   5 , Laure Morimont  4   5 , Marc Derive  6 , Lucie Jolly  6 , Luc Bertrand  1   7 , Pierre-François Laterre  8   9 , Sandrine Horman  1 , Christophe Beauloye  1   10
Affiliations

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

Mélanie Dechamps et al. Int J Mol Sci. .

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: COVID-19; coagulopathy; cytokine storm; inflammation; low dose dexamethasone.

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Conflict of interest statement

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.

Figures

Figure 1
Figure 1
Corticosteroid effects on endothelial activation (A) and coagulation (B) in critical COVID-19 patients. Scatter graphs of soluble biomarkers of endothelial activation and coagulation. Individual values (dots), mean (colored rectangle), and standard deviation are presented on the graphs. ICAM, intercellular adhesion molecule; INR, international normalized ratio; PAI-1, plasminogen activator inhibitor-1; TAT, thrombin–antithrombin complex; TF, tissue factor; TFPI, tissue factor pathway inhibitor; tPA, tissue plasminogen activator; VCAM, vascular cell adhesion molecule; vWF, von Willebrand factor. ** p < 0.01.
Figure 2
Figure 2
Corticosteroid effects on platelet activation (A) and NETosis (B) in critical COVID-19 patients. Scatter graphs of soluble biomarkers of platelet activation and NETosis. Individual values (dots), mean (colored rectangle), and standard deviation are presented on the graphs. ** p < 0.01 between the no DXM group and the DXM group. sP-selectin, soluble p-selectin; Cit-H3, citrullinated histone 3; MPO, myeloperoxidase; NE, neutrophil elastase.
Figure 3
Figure 3
Corticosteroid effects on ubiquitous inflammatory reaction in critical COVID-19 patients. Scatter graphs of ubiquitous proinflammatory cytokines. Individual values (dots), mean (colored rectangle), and standard deviation are presented on the graphs. * p < 0.05, ** p < 0.01 between the no DXM group and the DXM group. CRP, C-reactive protein; IL, interleukin; TNF α, tumor necrosis factor α; WBCs, white blood cells.
Figure 4
Figure 4
Corticosteroid effects on myeloid immune response in critical COVID-19 patients. Scatter graphs of myeloid inflammatory cytokines. Individual values (dots), mean (colored rectangle), and standard deviation are presented on the graphs. ** p < 0.01 between the no DXM group and the DXM group. IL, interleukin; IL-1ra, IL-1 receptor antagonist; MCP-1, monocyte chemoattractant protein 1; MIP, macrophage inflammatory protein-1α; sTREM-1, soluble triggering receptor expressed on myeloid cells 1.
Figure 5
Figure 5
Corticosteroid effects on lymphoid immune response in critical COVID-19 patients. Scatter graphs of lymphoid inflammatory cytokines. Individual values (dots), mean (colored rectangle), and standard deviation are presented on the graphs. ** p < 0.01, **** p < 0.0001 between the no DXM group and the DXM group. CD40L, CD40 ligand; IFNγ, interferon gamma; IL, interleukin; IP-10, interferon gamma-induced protein 10.
Figure 6
Figure 6
Overview of corticosteroid effects on the inflammatory and immune responses, endothelial and platelet activation, NETosis, and coagulopathy in patients with severe COVID-19.
See this image and copyright information in PMC

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