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

Smadja, David M.; Philippe, Aurélien; Bory, Olivier; Gendron, Nicolas; Beauvais, Agathe; Gruest, Maxime; Peron, Nicolas; Khider, Lina; Guerin, Coralie L.; Goudot, Guillaume; Levavasseur, Françoise; Duchemin, Jérome; Pene, Frédéric; Cheurfa, Cherifa; Szwebel, Tali‐Anne; Sourdeau, Elise; Planquette, Benjamin; Hauw‐Berlemont, Caroline; Hermann, Bertrand; Gaussem, Pascale; Samama, Charles‐Marc; Mirault, Tristan; Terrier, Benjamin; Sanchez, Olivier; Rance, Bastien; Fontenay, Michaela; Diehl, Jean‐Luc; Chocron, Richard

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.