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

Adult Aged Biomarkers / blood COVID-19 / blood Cross-Sectional Studies Endothelium, Vascular / physiopathology Female Hospital Mortality Humans Kaplan-Meier Estimate Male Middle Aged Molecular Weight Pandemics Paris / epidemiology Proportional Hazards Models Protein Multimerization SARS-CoV-2 Severity of Illness Index Thrombosis / blood von Willebrand Factor / chemistry

COVID-19 Endothelial activation Microthrombosis Mortality Multimers Von Willebrand factor

Journal

Angiogenesis

ISSN: 1573-7209

Titre abrégé: Angiogenesis

Pays: Germany

ID NLM: 9814575

Informations de publication

Date de publication:
08 2021

Historique:

received: 03 12 2020

accepted: 14 12 2020

pubmed: 16 1 2021

medline: 30 7 2021

entrez: 15 1 2021

Statut: ppublish

Résumé

Coronavirus disease 2019 (COVID-19) is a respiratory disease associated with endotheliitis and microthrombosis. To correlate endothelial dysfunction to in-hospital mortality in a bi-centric cohort of COVID-19 adult patients. 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. 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. 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.

Sections du résumé

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.

Identifiants

DOI: 10.1007/s10456-020-09762-6 PMID: 33449299 PMC: PMC7809553

pubmed: 33449299

doi: 10.1007/s10456-020-09762-6

pii: 10.1007/s10456-020-09762-6

pmc: PMC7809553

doi:

Substances chimiques

Biomarkers 0

von Willebrand Factor 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

Pagination

505-517

Subventions

Organisme : ANR

ID : SARCODO

Commentaires et corrections

Type : CommentIn

Informations de copyright

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