Endotheliopathy Marked by High von Willebrand Factor (vWF) Antigen in COVID-19 is Associated with Poor Outcome: A Systematic Review and Meta-analysis

Wibowo, Arief; Pranata, Raymond; Lim, Michael Anthonius; Akbar, Mohammad Rizki; Martha, Januar Wibawa

Background: In this systematic review and meta-analysis, we aimed to compare the level of von Willebrand Factor (vWF) antigen in patients with poor outcome compared to those without. Additionally, we also explored factors that may affect the difference in terms of vWF antigen between the two groups. Methods: A comprehensive literature search was performed using the PubMed, Embase, and Scopus databases from inception up until 7 April 2021. The main outcome was poor outcome, which is a composite of mortality and severe COVID-19. Results: There are 10 studies comprising of 996 patients included in this systematic review and meta-analysis. vWF antigen was higher in patients with poor outcome (standardized mean difference [SMD] 0.84 [0.45, 1.23], p<0.001; I(2): 87.3, p<0.001). Subgroup analysis on vWF antigen that uses percentage as unit (mean difference 121.6 [53.7, 189.4], p<0.001; I(2): 92.0, p<0.001). Meta-regression showed that the SMD between poor outcome and good outcome was affected by platelets (coefficient: 0.0061, p=0.001), d-dimer (coefficient: 0.0007, p=0.026), and factor VIII level (coefficient: 0.0057, p=0.031), but not by age (coefficient: -0.0610, p=0.440), gender (coefficient: 0.0135, p=0.698), obesity (coefficient: 0.0282, p=0.666), hypertension (coefficient: 0.0273, p=0.423), diabetes (coefficient: 0.0317, p=0.398), malignancy (coefficient: 0.0487, p=0.608). Conclusion: This meta-analysis showed that the level of vWF antigen was significantly higher in patients with poor outcome, signaling a marked endotheliopathy. Meta-regression showed that differences became larger as the number of platelets, d-dimer levels, and factor VIII levels increases.