Placental growth factor level in plasma predicts COVID-19 severity and in-hospital mortality.


Journal

Journal of thrombosis and haemostasis : JTH
ISSN: 1538-7836
Titre abrégé: J Thromb Haemost
Pays: England
ID NLM: 101170508

Informations de publication

Date de publication:
07 2021
Historique:
revised: 17 02 2021
received: 23 12 2020
accepted: 25 03 2021
pubmed: 9 4 2021
medline: 1 7 2021
entrez: 8 4 2021
Statut: ppublish

Résumé

Coronavirus disease 2019 (COVID-19) is a respiratory disease associated with vascular inflammation and endothelial injury. To correlate circulating angiogenic markers vascular endothelial growth factor A (VEGF-A), placental growth factor (PlGF), and fibroblast growth factor 2 (FGF-2) to in-hospital mortality in COVID-19 adult patients. Consecutive ambulatory and hospitalized patients with COVID-19 infection were enrolled. VEGF-A, PlGF, and FGF-2 were measured in each patient ≤48 h following admission. The study enrolled 237 patients with suspected COVID-19: 208 patients had a positive diagnostic for COVID-19, of whom 23 were mild outpatients and 185 patients hospitalized after admission. Levels of VEGF-A, PlGF, and FGF-2 significantly increase with the severity of the disease (P < .001). Using a logistic regression model, we found a significant association between the increase of FGF-2 or PlGF and mortality (odds ratio [OR] 1.11, 95% confidence interval [CI; 1.07-1.16], P < .001 for FGF-2 and OR 1.07 95% CI [1.04-1.10], P < .001 for PlGF) while no association were found for VEGF-A levels. Receiver operating characteristic curve analysis was performed and we identified PlGF above 30 pg/ml as the best predictor of in-hospital mortality in COVID-19 patients. Survival analysis for PlGF confirmed its interest for in-hospital mortality prediction, by using a Kaplan-Meier survival curve (P = .001) and a Cox proportional hazard model adjusted to age, body mass index, D-dimer, and C-reactive protein (3.23 95% CI [1.29-8.11], P = .001). Angiogenic factor PlGF is a relevant predictive factor for in-hospital mortality in COVID-19 patients. More than a biomarker, we hypothesize that PlGF blocking strategies could be a new interesting therapeutic approach in COVID-19.

Sections du résumé

BACKGROUND
Coronavirus disease 2019 (COVID-19) is a respiratory disease associated with vascular inflammation and endothelial injury.
OBJECTIVES
To correlate circulating angiogenic markers vascular endothelial growth factor A (VEGF-A), placental growth factor (PlGF), and fibroblast growth factor 2 (FGF-2) to in-hospital mortality in COVID-19 adult patients.
METHODS
Consecutive ambulatory and hospitalized patients with COVID-19 infection were enrolled. VEGF-A, PlGF, and FGF-2 were measured in each patient ≤48 h following admission.
RESULTS
The study enrolled 237 patients with suspected COVID-19: 208 patients had a positive diagnostic for COVID-19, of whom 23 were mild outpatients and 185 patients hospitalized after admission. Levels of VEGF-A, PlGF, and FGF-2 significantly increase with the severity of the disease (P < .001). Using a logistic regression model, we found a significant association between the increase of FGF-2 or PlGF and mortality (odds ratio [OR] 1.11, 95% confidence interval [CI; 1.07-1.16], P < .001 for FGF-2 and OR 1.07 95% CI [1.04-1.10], P < .001 for PlGF) while no association were found for VEGF-A levels. Receiver operating characteristic curve analysis was performed and we identified PlGF above 30 pg/ml as the best predictor of in-hospital mortality in COVID-19 patients. Survival analysis for PlGF confirmed its interest for in-hospital mortality prediction, by using a Kaplan-Meier survival curve (P = .001) and a Cox proportional hazard model adjusted to age, body mass index, D-dimer, and C-reactive protein (3.23 95% CI [1.29-8.11], P = .001).
CONCLUSION
Angiogenic factor PlGF is a relevant predictive factor for in-hospital mortality in COVID-19 patients. More than a biomarker, we hypothesize that PlGF blocking strategies could be a new interesting therapeutic approach in COVID-19.

Identifiants

pubmed: 33830623
doi: 10.1111/jth.15339
pmc: PMC8250221
pii: S1538-7836(22)01818-9
doi:

Substances chimiques

Biomarkers 0
Vascular Endothelial Growth Factor A 0
Placenta Growth Factor 144589-93-5

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

1823-1830

Subventions

Organisme : Agence Nationale de la Recherche / Fondation de France
ID : SARCODO
Organisme : Assistance Publique - Hôpitaux de Paris
ID : Mecenat COVID

Informations de copyright

© 2021 International Society on Thrombosis and Haemostasis.

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Auteurs

David M Smadja (DM)

Université de Paris, Innovative Therapies in Haemostasis, INSERM, Paris, France.
Hematology Department and Biosurgical Research Lab (Carpentier Foundation), Assistance Publique Hôpitaux de Paris-Centre (APHP-CUP), Paris, France.

Aurélien Philippe (A)

Université de Paris, Innovative Therapies in Haemostasis, INSERM, Paris, France.
Hematology Department and Biosurgical Research Lab (Carpentier Foundation), Assistance Publique Hôpitaux de Paris-Centre (APHP-CUP), Paris, France.

Olivier Bory (O)

Université de Paris, Emergency Department, Assistance Publique Hôpitaux de Paris-Centre (APHP-CUP), Paris, France.

Nicolas Gendron (N)

Université de Paris, Innovative Therapies in Haemostasis, INSERM, Paris, France.
Hematology Department and Biosurgical Research Lab (Carpentier Foundation), Assistance Publique Hôpitaux de Paris-Centre (APHP-CUP), Paris, France.

Agathe Beauvais (A)

Université de Paris, Emergency Department, Assistance Publique Hôpitaux de Paris-Centre (APHP-CUP), Paris, France.

Maxime Gruest (M)

Université de Paris, Innovative Therapies in Haemostasis, INSERM, Paris, France.
Hematology Department and Biosurgical Research Lab (Carpentier Foundation), Assistance Publique Hôpitaux de Paris-Centre (APHP-CUP), Paris, France.

Nicolas Peron (N)

Université de Paris, Intensive Care Department, Assistance Publique Hôpitaux de Paris-Centre (APHP-CUP), Paris, France.

Lina Khider (L)

Université de Paris, Vascular Medicine Department and Biosurgical Research Lab (Carpentier Foundation), Assistance Publique Hôpitaux de Paris-Centre (APHP-CUP), Paris, France.

Coralie L Guerin (CL)

Université de Paris, Innovative Therapies in Haemostasis, INSERM, Paris, France.
Curie Institute, Cytometry Department, Paris, France.

Guillaume Goudot (G)

Université de Paris, Vascular Medicine Department and Biosurgical Research Lab (Carpentier Foundation), Assistance Publique Hôpitaux de Paris-Centre (APHP-CUP), Paris, France.

Françoise Levavasseur (F)

Université de Paris, Institut Cochin, INSERM, Paris, France.
Hematology Department Assistance Publique Hôpitaux de Paris-Centre (APHP-CUP), Paris, France.

Jérome Duchemin (J)

Université de Paris, Institut Cochin, INSERM, Paris, France.
Hematology Department Assistance Publique Hôpitaux de Paris-Centre (APHP-CUP), Paris, France.

Frédéric Pene (F)

Internal Medicine Department, Assistance Publique Hôpitaux de Paris-Centre (APHP-CUP), Paris, France.

Cherifa Cheurfa (C)

Intensive Care Medicine and Reanimation Department, Assistance Publique Hôpitaux de Paris-Centre (APHP-CUP), Paris, France.

Tali-Anne Szwebel (TA)

Internal Medicine Department, Assistance Publique Hôpitaux de Paris-Centre (APHP-CUP), Paris, France.

Elise Sourdeau (E)

Emergency Unit, Hôpital Hôtel-Dieu, Assistance Publique Hôpitaux de Paris-Centre (APHP-CUP), Paris, France.

Benjamin Planquette (B)

Université de Paris, Innovative Therapies in Haemostasis, INSERM, Paris, France.
Respiratory Medicine Department and Biosurgical Research Lab (Carpentier Foundation), Assistance Publique Hôpitaux de Paris-Centre (APHP-CUP), Paris, France.

Caroline Hauw-Berlemont (C)

Université de Paris, Intensive Care Department, Assistance Publique Hôpitaux de Paris-Centre (APHP-CUP), Paris, France.

Bertrand Hermann (B)

Université de Paris, Intensive Care Department, Assistance Publique Hôpitaux de Paris-Centre (APHP-CUP), Paris, France.

Pascale Gaussem (P)

Université de Paris, Innovative Therapies in Haemostasis, INSERM, Paris, France.
Hematology Department and Biosurgical Research Lab (Carpentier Foundation), Assistance Publique Hôpitaux de Paris-Centre (APHP-CUP), Paris, France.

Charles-Marc Samama (CM)

Intensive Care Medicine and Reanimation Department, Assistance Publique Hôpitaux de Paris-Centre (APHP-CUP), Paris, France.

Tristan Mirault (T)

Université de Paris, PARCC, INSERM, Paris, France.
Vascular Medicine Department, Assistance Publique - Hôpitaux de Paris-Centre (APHP-CUP), Paris, France.

Benjamin Terrier (B)

Internal Medicine Department, Assistance Publique Hôpitaux de Paris-Centre (APHP-CUP), Paris, France.
Université de Paris, PARCC, INSERM, Paris, France.

Olivier Sanchez (O)

Emergency Unit, Hôpital Hôtel-Dieu, Assistance Publique Hôpitaux de Paris-Centre (APHP-CUP), Paris, France.

Bastien Rance (B)

Université de Paris, Department of Medical Informatics, AP-HP, Georges Pompidou European Hospital, Paris, France.

Michaela Fontenay (M)

Université de Paris, Institut Cochin, INSERM, Paris, France.
Hematology Department Assistance Publique Hôpitaux de Paris-Centre (APHP-CUP), Paris, France.

Jean-Luc Diehl (JL)

Université de Paris, Innovative Therapies in Haemostasis, INSERM, Paris, France.
Intensive Care Unit and Biosurgical Research Lab (Carpentier Foundation), Assistance Publique - Hôpitaux de Paris-Centre (APHP-CUP), Paris, France.

Richard Chocron (R)

Université de Paris, PARCC, INSERM U970, Paris, France.
Emergency Department, AH-HP-Centre Université de Paris (APHP-CUP), Paris, France.

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