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
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.
['Smadja|David M|DM|0000-0001-7731-9202', 'Philippe|Aurélien|A|', 'Bory|Olivier|O|0000-0001-7909-3905', 'Gendron|Nicolas|N|0000-0003-4852-4738', 'Beauvais|Agathe|A|', 'Gruest|Maxime|M|', 'Peron|Nicolas|N|', 'Khider|Lina|L|', 'Guerin|Coralie L|CL|', 'Goudot|Guillaume|G|', 'Levavasseur|Françoise|F|', 'Duchemin|Jérome|J|', 'Pene|Frédéric|F|', 'Cheurfa|Cherifa|C|', 'Szwebel|Tali-Anne|TA|', 'Sourdeau|Elise|E|', 'Planquette|Benjamin|B|', 'Hauw-Berlemont|Caroline|C|', 'Hermann|Bertrand|B|', 'Gaussem|Pascale|P|', 'Samama|Charles-Marc|CM|', 'Mirault|Tristan|T|', 'Terrier|Benjamin|B|', 'Sanchez|Olivier|O|', 'Rance|Bastien|B|', 'Fontenay|Michaela|M|', 'Diehl|Jean-Luc|JL|', 'Chocron|Richard|R|']
D000328:Adult D015415:Biomarkers D000086382:COVID-19 D005260:Female D017052:Hospital Mortality D006801:Humans D000072483:Placenta Growth Factor D000086402:SARS-CoV-2 D042461:Vascular Endothelial Growth Factor A
placental growth factor COVID-19 mortality PlGF FGF-2 angiogenesis