{
  "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.",
  "abstract_shown": true,
  "affiliations": [
    "Medical Intensive Care Unit, North Hospital, Assistance Publique-Hôpitaux de Marseille (AP-HM), Chemin des Bourrely, 13015 Marseille, France",
    "Centre 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",
    "Hematology Laboratory, La Timone University Hospital of Marseille, 13005 Marseille, France",
    "Clinique des Bronches Allergies et Sommeil, CIC 9502, Hôpital Nord, AP-HM, Aix Marseille University, Chemin des Bourrely, 13015 Marseille, France",
    "CNRS, EFS, ADES, Aix Marseille University, 13015 Marseille, France",
    "Centre d’Etudes et de Recherches sur les Services de Santé et Qualité de vie EA 3279, 13005 Marseille, France",
    "Clinical Research Department, Assistance Publique Hôpitaux de Marseille, 13005 Marseille, France"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 16,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Giovanni Bousquet",
      "orcid": "0000-0002-9818-6792"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Romaric Lacroix"
    },
    {
      "affs": [
        1,
        3,
        4
      ],
      "name": "Laurie Pahus",
      "orcid": "0000-0002-5265-2874"
    },
    {
      "affs": [
        0
      ],
      "name": "Sabine Valera"
    },
    {
      "affs": [
        2
      ],
      "name": "Nathalie Hezard"
    },
    {
      "affs": [
        2
      ],
      "name": "Laurent Arnaud"
    },
    {
      "affs": [
        2
      ],
      "name": "Evelyne Abdili"
    },
    {
      "affs": [
        5,
        6
      ],
      "name": "Karine Baumstarck",
      "orcid": "0000-0003-3602-6766"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Damien Barrau",
      "orcid": "0009-0007-8661-0094"
    },
    {
      "affs": [
        1,
        3,
        4
      ],
      "name": "Pascal Chanez"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Françoise Dignat-George"
    },
    {
      "affs": [
        0,
        5
      ],
      "name": "Laurent Papazian"
    },
    {
      "affs": [
        0,
        5
      ],
      "name": "Jean-Marie Forel"
    },
    {
      "affs": [
        0,
        5
      ],
      "name": "Sami Hraiech"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Pierre Morange"
    },
    {
      "affs": [
        0,
        5
      ],
      "name": "Christophe Guervilly",
      "orcid": "0000-0001-9066-6591"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/06q5hbmn9zzb2.bib",
  "cited_by": 0,
  "doi": "10.3390/jcm15218444",
  "fulltext_url": null,
  "id": "06q5hbmn9zzb2",
  "issns": [
    "2077-0383"
  ],
  "landing_url": "https://www.mdpi.com/2077-0383/15/21/8444",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [],
  "openalex": null,
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-29",
  "publisher": "MDPI AG",
  "ris": "https://research.draconitic.com/paper/06q5hbmn9zzb2.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:20:01Z",
      "native_id": "10.3390/jcm15218444",
      "source": "crossref",
      "url": "https://www.mdpi.com/2077-0383/15/21/8444"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "journal-openalex:F27",
      "subfield": "general"
    }
  ],
  "title": "Multipathway Biomarker Profiling of Immunothrombosis in Moderate and Severe COVID-19",
  "title_text": "Multipathway Biomarker Profiling of Immunothrombosis in Moderate and Severe COVID-19",
  "type": "peer-reviewed",
  "updated_at": "2026-10-31T00:21:07Z",
  "url": "https://research.draconitic.com/paper/06q5hbmn9zzb2",
  "venue": "Journal of Clinical Medicine",
  "versions": []
}