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.

COVID-19 and biomarkers of thrombosis: focus on von Willebrand factor and extracellular vesicles

“…Plasma levels of ADAMTS13 inhibitors like IL-6, thrombospondin and platelet factor 4 are often elevated in patients with severe COVID-19[36]. Other investigators and groups have drawn similar conclusions[37,[38][39][40][41].Henry et al[42] identified a lower ADAMTS13 activity/VWF:Ag ratio in patients with COVID-19 and acute kidney injury and those who developed infection compared to patient with neither. In a prospective study of 50 patients with COVID-19 requiring hospital admission[34], higher D-dimer, fibrinogen and VWF:Ag levels and lower ADAMTS13 activity were observed compared to patients not requiring hospitalization.…”

Role of Tocilizumab in Down Regulating sCD163 Plasmatic Levels in a Cohort of COVID-19 Patients

“…Elevated CD163 expression on alveolar macrophages has been reported in patients with chronic obstructive pulmonary disease (BPCO) and in idiopathic pulmonary fibrosis ( 9 ). Several authors reported an increment of sCD163 plasmatic levels with worsening COVID-19 severity, underlining a preponderant role for monocyte-macrophage activation in the development of immunopathology of COVID-19 patients ( 6 , 15 – 17 ).…”

Prognostic value of von Willebrand factor and ADAMTS13 in patients with COVID-19: A systematic review and meta-analysis

“…The final full-text review included 163 reports, from which 123 studies did not meet the inclusion criteria and were excluded. A total of 40 studies comprising of 3764 patients met the including criteria and were included in this systematic review and meta-analysis [24] , [49] , [50] , [51] , [52] , [53] , [54] , [55] , [56] , [57] , [58] , [59] , [60] , [61] , [62] , [63] , [64] , [65] , [66] , [67] , [68] , [69] , [70] , [71] , [72] , [73] , [74] , [75] , [76] , [77] , [78] , [79] , [80] , [81] , [82] , [83] , [84] , [85] , [86] , [87] . Fig.…”