Multipathway Biomarker Profiling of Immunothrombosis in Moderate and Severe COVID-19
7 affiliations
- 1Medical Intensive Care Unit, North Hospital, Assistance Publique-Hôpitaux de Marseille (AP-HM), Chemin des Bourrely, 13015 Marseille, France
- 2Centre de Recherche en CardioVasculaire et Nutrition (C2VN), INSERM 1263, Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE) 1260, Aix Marseille University, 13005 Marseille, France
- 3Hematology Laboratory, La Timone University Hospital of Marseille, 13005 Marseille, France
- 4Clinique des Bronches Allergies et Sommeil, CIC 9502, Hôpital Nord, AP-HM, Aix Marseille University, Chemin des Bourrely, 13015 Marseille, France
- 5CNRS, EFS, ADES, Aix Marseille University, 13015 Marseille, France
- 6Centre d’Etudes et de Recherches sur les Services de Santé et Qualité de vie EA 3279, 13005 Marseille, France
- 7Clinical Research Department, Assistance Publique Hôpitaux de Marseille, 13005 Marseille, France
Abstract
Background/Objectives: Coronavirus disease 2019 (COVID-19) is associated with immunothrombosis involving endothelial dysfunction and coagulation activation. We aimed to compare biomarkers spanning multiple immunothrombotic pathways between patients with moderate and severe COVID-19 at baseline and according to clinical outcome. Secondary analyses compared biomarker levels at days 3 and 7. Methods: This prospective observational study included 42 hospitalized patients with COVID-19 enrolled between April 2020 and January 2021, comprising 21 with moderate and 21 with severe disease. Biomarkers of coagulation, endothelial dysfunction, endogenous anticoagulant pathways, fibrinolysis, and extracellular vesicle-mediated activity were measured at baseline and on days 3 and 7. The prespecified ventilation/death composite included invasive mechanical ventilation already ongoing at baseline or initiated subsequently and/or death by day 28. Results: Seventeen patients (40.5%) met the composite criterion, including 12 patients already receiving invasive mechanical ventilation at baseline. At baseline, severe disease was associated with higher D-dimer (1.74 [0.87–3.67] vs. 0.68 [0.46–0.94] µg/mL FEU), free tissue factor pathway inhibitor (TFPI; 55.00 [38.00–109.00] vs. 16.00 [14.00–29.00] ng/mL), extracellular vesicle-associated tissue factor activity (EV-TF; 28.86 [13.61–48.72] vs. 5.00 [5.00–5.70] fM), and extracellular vesicle-associated plasmin generation capacity (EV-PGC; 93.36 [41.60–303.10] vs. 24.50 [16.14–35.74] fM; all p < 0.01). Exploratory ROC analyses further illustrated the separation of these biomarker distributions between the predefined clinical groups. Conclusions: Severe COVID-19 and unfavorable outcomes were associated with baseline differences in biomarkers spanning several immunothrombotic pathways, some of which remained detectable at days 3 and 7. Interpretation of the marked TFPI elevation is limited by differences in heparin exposure between severity groups. These exploratory findings require confirmation in larger cohorts, and their incremental value beyond routine clinical assessment remains untested. Outcome analyses largely reflected baseline severity, with only five subsequent events.
Related
- Remission in moderate-to-severe pediatric asthma: Definitions, assessment, prevalence, predictors, and outcomes—a scoping review
- Prognostic Value of the Modified Endothelial Activation and Stress Index (m-EASIX) for 90-Day Mortality in Patients with Moderate-to-Severe Hypercalcemia of Malignancy
- Coexisting Moderate-to-Severe Tricuspid Regurgitation and Renal Dysfunction Identify a High-Risk Group After Transcatheter Aortic Valve Replacement
- A randomized double-blind non-inferiority trial comparing LUCENTRA with DYSPORT for moderate-to-severe glabellar line improvement
- Oscillometry-defined small airway dysfunction as a predictor of moderate-to-severe exacerbations in COPD: a systematic review and meta-analysis
BibTeX
@article{bousquet2026multipathway,
title = {{Multipathway Biomarker Profiling of Immunothrombosis in Moderate and Severe COVID-19}},
author = {Giovanni Bousquet and Romaric Lacroix and Laurie Pahus and Sabine Valera and Nathalie Hezard and Laurent Arnaud and Evelyne Abdili and Karine Baumstarck and Damien Barrau and Pascal Chanez and Françoise Dignat-George and Laurent Papazian and Jean-Marie Forel and Sami Hraiech and Pierre Morange and Christophe Guervilly},
journal = {Journal of Clinical Medicine},
year = {2026},
month = oct,
doi = {10.3390/jcm15218444},
url = {https://www.mdpi.com/2077-0383/15/21/8444},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Multipathway Biomarker Profiling of Immunothrombosis in Moderate and Severe COVID-19
AU - Giovanni Bousquet
AU - Romaric Lacroix
AU - Laurie Pahus
AU - Sabine Valera
AU - Nathalie Hezard
AU - Laurent Arnaud
AU - Evelyne Abdili
AU - Karine Baumstarck
AU - Damien Barrau
AU - Pascal Chanez
AU - Françoise Dignat-George
AU - Laurent Papazian
AU - Jean-Marie Forel
AU - Sami Hraiech
AU - Pierre Morange
AU - Christophe Guervilly
PY - 2026
DA - 2026/10/29
JO - Journal of Clinical Medicine
DO - 10.3390/jcm15218444
UR - https://www.mdpi.com/2077-0383/15/21/8444
AB - Background/Objectives: Coronavirus disease 2019 (COVID-19) is associated with immunothrombosis involving endothelial dysfunction and coagulation activation. We aimed to compare biomarkers spanning multiple immunothrombotic pathways between patients with moderate and severe COVID-19 at baseline and according to clinical outcome. Secondary analyses compared biomarker levels at days 3 and 7. Methods: This prospective observational study included 42 hospitalized patients with COVID-19 enrolled between April 2020 and January 2021, comprising 21 with moderate and 21 with severe disease. Biomarkers of coagulation, endothelial dysfunction, endogenous anticoagulant pathways, fibrinolysis, and extracellular vesicle-mediated activity were measured at baseline and on days 3 and 7. The prespecified ventilation/death composite included invasive mechanical ventilation already ongoing at baseline or initiated subsequently and/or death by day 28. Results: Seventeen patients (40.5%) met the composite criterion, including 12 patients already receiving invasive mechanical ventilation at baseline. At baseline, severe disease was associated with higher D-dimer (1.74 [0.87–3.67] vs. 0.68 [0.46–0.94] µg/mL FEU), free tissue factor pathway inhibitor (TFPI; 55.00 [38.00–109.00] vs. 16.00 [14.00–29.00] ng/mL), extracellular vesicle-associated tissue factor activity (EV-TF; 28.86 [13.61–48.72] vs. 5.00 [5.00–5.70] fM), and extracellular vesicle-associated plasmin generation capacity (EV-PGC; 93.36 [41.60–303.10] vs. 24.50 [16.14–35.74] fM; all p < 0.01). Exploratory ROC analyses further illustrated the separation of these biomarker distributions between the predefined clinical groups. Conclusions: Severe COVID-19 and unfavorable outcomes were associated with baseline differences in biomarkers spanning several immunothrombotic pathways, some of which remained detectable at days 3 and 7. Interpretation of the marked TFPI elevation is limited by differences in heparin exposure between severity groups. These exploratory findings require confirmation in larger cohorts, and their incremental value beyond routine clinical assessment remains untested. Outcome analyses largely reflected baseline severity, with only five subsequent events.
SN - 2077-0383
ER -