Association between dexamethasone treatment and the host response in COVID-19 patients admitted to the general ward

Brabander, Justin de; Michels, Erik H.A.; Linge, Christine C. A. van; Douma, Renée A.; Engelen, Tjitske S. R. van; Agtmael, Michiel A. van; Algera, Anne Geke; Appelman, Brent; Baarle, Frank E.H.P. van; Bax, Diane; Beudel, Martijn; Bogaard, Harm Jan; Bomers, Marije; Bonta, Peter I.; Bos, Lieuwe; Botta, Michela; Bree, Godelieve J. de; Bruin, Sanne de; Bugiani, Marianne; Bulle, Esther; Chouchane, Osoul; Cloherty, Alex; Buis, David T.P.; Rotte, Maurits C F J de; Dijkstra, Mirjam; Dongelmans, Dave A.; Dujardin, Romein W. G.; Elbers, Paul; Fleuren, Lucas M.; Geerlings, Suzanne E.; Geijtenbeek, T.B.H.; Girbes, Armand R.J.; Goorhuis, Abraham; Grobusch, Martin P.; Hafkamp, Florianne; Hagens, Laura A.; Hamann, Jörg; Harris, Vanessa; Hemke, Robert; Hermans, Sabine; Heunks, Leo; Hollmann, Markus W.; Horn, Janneke; Hovius, Joppe W.; Jong, Menno D. de; Koning, Rutger; Lim, Endry H T; Mourik, Niels van; Nellen, Jeannine; Nossent, Esther J.; Paulus, Frederique; Peters, Edgar; Piña-Fuentes, Dan; Preckel, Bennedikt; Prins, Jan M.; Reijnders, Tom D.Y.; Schinkel, Michiel; Schrauwen, Femke A. P.; Schultz, Marcus J.; Schuurman, Alex R.; Schuurmans, Jaap; Sigalof, Kim; Slim, Marleen A.; Smeele, Patrick; Smit, Marry R.; Stijnis, Cornelis; Teunissen, Charlotte E.; Thoral, Patrick; Tsonas, Anissa M.; Tuinman, Pieter R.; Valk, Marc van der; Veelo, Denise P.; Volleman, Carolien; Vries, Heder de; Vught, Lonneke A. van; Vugt, Michèle van; Wouters, Dorien; Zwinderman, Koos; Brouwer, Matthijs C.; Vlaar, Alexander P. J.; Beek, Diederik van de; Wiersinga, W. Joost; Poll, Tom van der

doi:10.1186/s12931-022-02060-3

Cited by 7 publications

(4 citation statements)

References 11 publications

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“…IL-6 and TNF-alpha (TNF-α)) that may be affected by targeting CD14. 17 , 18 , 19 , 20 Presepsin, an N-terminal fragment of full length CD14 that is generated in the setting of CD14-dependent innate immune activation, and a marker of CD14 signaling, 9 , 21 has been associated with clinical outcomes in observational studies of patients with severe COVID-19. 22 , 23 , 24 , 25 , 26 In early phase clinical trials in bacterial sepsis and ARDS, IC14 reduced systemic inflammation (e.g.…”

Section: Introductionmentioning

confidence: 99%

Phase 2, randomized, double-blind, placebo-controlled multi-center trial of the clinical and biological effects of anti-CD14 treatment in hospitalized patients with COVID-19 pneumonia

Mabrey

Nian

et al. 2023

eBioMedicine

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Section: Introductionmentioning

confidence: 99%

Phase 2, randomized, double-blind, placebo-controlled multi-center trial of the clinical and biological effects of anti-CD14 treatment in hospitalized patients with COVID-19 pneumonia

Mabrey

Nian

et al. 2023

eBioMedicine

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“…Although this bias is inevitable in our design, its impact may be relatively modest. We previously showed that corticosteroid treatment given shortly before sampling only minimally affects plasma biomarkers ( 44 ). In addition, the proportion of patients receiving corticosteroids before sampling was similar between clusters and had no significant value in predicting cluster membership based on clinical variables ( see Table E9).…”

Section: Discussionmentioning

confidence: 99%

Host Response Changes and Their Association with Mortality in COVID-19 Patients with Lymphopenia

Michels,

Appelman,

de Brabander

et al. 2024

Am J Respir Crit Care Med

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Rationale Lymphopenia in coronavirus disease (COVID-19) is associated with increased mortality. Objectives To explore the association between lymphopenia, host response aberrations, and mortality in patients with lymphopenic COVID-19. Methods We determined 43 plasma biomarkers reflective of four pathophysiological domains: endothelial cell and coagulation activation, inflammation and organ damage, cytokine release, and chemokine release. We explored if decreased concentrations of lymphocyte-derived proteins in patients with lymphopenia were associated with an increase in mortality. We sought to identify host response phenotypes in patients with lymphopenia by cluster analysis of plasma biomarkers. Measurements and Main Results A total of 439 general ward patients with COVID-19 were stratified by baseline lymphocyte counts: normal (>1.0 × 10 9 /L; n = 167), mild lymphopenia (>0.5 to ⩽1.0 × 10 9 /L; n = 194), and severe lymphopenia (⩽0.5 × 10 9 /L; n = 78). Lymphopenia was associated with alterations in each host response domain. Lymphopenia was associated with increased mortality. Moreover, in patients with lymphopenia ( n = 272), decreased concentrations of several lymphocyte-derived proteins (e.g., CCL5, IL-4, IL-13, IL-17A) were associated with an increase in mortality (at P < 0.01 or stronger significance levels). A cluster analysis revealed three host response phenotypes in patients with lymphopenia: “hyporesponsive” (23.2%), “hypercytokinemic” (36.4%), and “inflammatory-injurious” (40.4%), with substantially differing mortality rates of 9.5%, 5.1%, and 26.4%, respectively. A 10-biomarker model accurately predicted these host response phenotypes in an external cohort with similar mortality distribution. The inflammatory-injurious phenotype showed a remarkable combination of relatively high inflammation and organ damage markers with high antiinflammatory cytokine levels yet low proinflammatory cytokine levels. Conclusions Lymphopenia in COVID-19 signifies a heterogenous group of patients with distinct host response features. Specific host responses contribute to lymphopenia-associated mortality in COVID-19, including reduced CCL5 levels.

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“…With regard to COVID-19, two studies showed results that were consistent with our study. In the first, for patients admitted to the general ward with lower severity scores than in our study, DXM that was administered within 19 h of collection reduced plasma IL-6 and IL-1ra levels but did not influence COVID-19 coagulation disorders [ 45 ]. In the second, for patients admitted to intensive care, DXM decreased plasma levels of cytokines (IL-1, IL-2, IL-6, IL-8, IL-10, IL-17, IFNγ, and MIP-1) and endothelial markers but biomarkers of coagulopathy were not measured [ 35 ].…”

Section: Discussionmentioning

confidence: 99%

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

Dechamps

Poortere

Octave

et al. 2023

IJMS

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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.

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Association between dexamethasone treatment and the host response in COVID-19 patients admitted to the general ward

Cited by 7 publications

References 11 publications

Phase 2, randomized, double-blind, placebo-controlled multi-center trial of the clinical and biological effects of anti-CD14 treatment in hospitalized patients with COVID-19 pneumonia

Phase 2, randomized, double-blind, placebo-controlled multi-center trial of the clinical and biological effects of anti-CD14 treatment in hospitalized patients with COVID-19 pneumonia

Host Response Changes and Their Association with Mortality in COVID-19 Patients with Lymphopenia

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

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