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15.01.2021 | COVID-19 | Original Paper Zur Zeit gratis

Circulating Von Willebrand factor and high molecular weight multimers as markers of endothelial injury predict COVID-19 in-hospital mortality

verfasst von: Aurélien Philippe, Richard Chocron, Nicolas Gendron, Olivier Bory, Agathe Beauvais, Nicolas Peron, Lina Khider, Coralie L. Guerin, Guillaume Goudot, Françoise Levasseur, Christophe Peronino, Jerome Duchemin, Julie Brichet, Elise Sourdeau, Florence Desvard, Sébastien Bertil, Frédéric Pene, Cherifa Cheurfa, Tali-Anne Szwebel, Benjamin Planquette, Nadia Rivet, Georges Jourdi, Caroline Hauw-Berlemont, Bertrand Hermann, Pascale Gaussem, Tristan Mirault, Benjamin Terrier, Olivier Sanchez, Jean-Luc Diehl, Michaela Fontenay, David M. Smadja

Erschienen in: Angiogenesis | Ausgabe 3/2021

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Abstract

Background

Coronavirus disease 2019 (COVID-19) is a respiratory disease associated with endotheliitis and microthrombosis.

Objectives

To correlate endothelial dysfunction to in-hospital mortality in a bi-centric cohort of COVID-19 adult patients.

Methods

Consecutive ambulatory and hospitalized patients with laboratory-confirmed COVID-19 were enrolled. A panel of endothelial biomarkers and von Willebrand factor (VWF) multimers were measured in each patient ≤ 48 h following admission.

Results

Study enrolled 208 COVID-19 patients of whom 23 were mild outpatients and 189 patients hospitalized after admission. Most of endothelial biomarkers tested were found increased in the 89 critical patients transferred to intensive care unit. However, only von Willebrand factor antigen (VWF:Ag) scaled according to clinical severity, with levels significantly higher in critical patients (median 507%, IQR 428–596) compared to non-critical patients (288%, 230–350, p < 0.0001) or COVID-19 outpatients (144%, 133–198, p = 0.007). Moreover, VWF high molecular weight multimers (HMWM) were significantly higher in critical patients (median ratio 1.18, IQR 0.86–1.09) compared to non-critical patients (0.96, 1.04–1.39, p < 0.001). Among all endothelial biomarkers measured, ROC curve analysis identified a VWF:Ag cut-off of 423% as the best predictor for in-hospital mortality. The accuracy of VWF:Ag was further confirmed in a Kaplan–Meier estimator analysis and a Cox proportional Hazard model adjusted on age, BMI, C-reactive protein and d-dimer levels.

Conclusion

VWF:Ag is a relevant predictive factor for in-hospital mortality in COVID-19 patients. More than a biomarker, we hypothesize that VWF, including excess of HMWM forms, drives microthrombosis in COVID-19.

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Titel: Circulating Von Willebrand factor and high molecular weight multimers as markers of endothelial injury predict COVID-19 in-hospital mortality
verfasst von: Aurélien Philippe
Richard Chocron
Nicolas Gendron
Olivier Bory
Agathe Beauvais
Nicolas Peron
Lina Khider
Coralie L. Guerin
Guillaume Goudot
Françoise Levasseur
Christophe Peronino
Jerome Duchemin
Julie Brichet
Elise Sourdeau
Florence Desvard
Sébastien Bertil
Frédéric Pene
Cherifa Cheurfa
Tali-Anne Szwebel
Benjamin Planquette
Nadia Rivet
Georges Jourdi
Caroline Hauw-Berlemont
Bertrand Hermann
Pascale Gaussem
Tristan Mirault
Benjamin Terrier
Olivier Sanchez
Jean-Luc Diehl
Michaela Fontenay
David M. Smadja
Publikationsdatum: 15.01.2021
Verlag: Springer Netherlands
Schlagwort: COVID-19
Erschienen in: Angiogenesis / Ausgabe 3/2021
Print ISSN: 0969-6970
Elektronische ISSN: 1573-7209
DOI: https://doi.org/10.1007/s10456-020-09762-6

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Methods

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