Plasma Von Willebrand Factor Levels Predict Survival in COVID-19 Patients Across the Entire Spectrum of Disease Severity

Abstract

Background: Characterization of reticulo-endothelial activation in COVID-19 may guide treatment.

Objectives: To assess reticulo-endothelial activation and its correlation with disease severity and death in patients across the entire spectrum of COVID-19 severity.

Methods: Consecutive hospitalized COVID-19 patients were studied, with similar number of patients in each disease severity category. Baseline serum ferritin, sCD163 (macrophage activation markers) and plasma von Willebrand factor (VWF) antigen (endothelial activation marker) levels were studied. Clinical parameters and plasma D-dimer levels were also studied. The study parameters were correlated with COVID-19 severity and survival.

Results: The 143 patients (104 males [80%], age 54 [42 - 65] years, median [inter-quartile range]) presented 4 (3-7) days after symptom onset. Thirty-four patients had mild disease, 36 had moderate disease, 36 had severe disease and 37 had critical disease at baseline. With increasing COVID-19 severity, ferritin, sCD163, VWF and D-dimer levels significantly increased at baseline, however, 139 patients had normal sCD163 levels. Of the reticulo-endothelial markers, VWF level independently correlated with COVID-19 severity and with survival. VWF level > 332.6 units/dl correlated with COVID-19 severity (odds ratio [OR]: 2.77 [95% confidence interval (C.I): 1.1 - 6.99], p value: 0.031) and in-hospital death (OR [95% CI]: 29.28 [5.2 - 165], p value < 0.001).

Conclusions: Reticulo-endothelial activation markers increased incrementally with worsening COVID-19 severity. Baseline endothelial activation marker (VWF), and not macrophage activation markers, independently correlated with COVID-19 severity and death.

Keywords: COVID-19; Endothelium; Reticulo-endothelial system; Von Willebrand factor.

Fig. 1

Plasma von Willebrand factor antigen levels in 143 COVID-19 patients classified as per WHO criteria for disease severity at admission to hospital. The long horizontal lines represent the median and short horizontal lines represent inter-quartile range (IQR)

Fig. 2

Baseline plasma von Willebrand factor antigen levels in 143 COVID-19 patients who were discharged alive (n = 120) compared those who died (n = 23). The long horizontal lines represent the median and short horizontal lines represent inter-quartile range (IQR)