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

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a respiratory disease associated with vascular inflammation and endothelial injury. OBJECTIVES: Correlate circulating angiogenic markers VEGF-A, PlGF and 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: 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<0.001). Using a logistic regression model we found a significant association between the increase of FGF-2 or PlGF and mortality (OR 1.11, 95% CI [1.07-1.16], p<0.001 for FGF-2 and OR 1.07 95% CI [1.04-1.10], p<0.001 for PlGF) while no association were found for VEGF-A levels. ROC 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 curves (p=0.001) and a Cox proportional hazard model adjusted to age, body mass index, D-dimer and CRP (3.23 95% CI [1.29-8.11], p=0.001). 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.