Endotheliopathy marked by high von Willebrand factor (vWF) antigen in COVID-19 is associated with poor outcome: a systematic review and meta-analysis

Background This systematic review and meta-analysis aimed to compare the levels of von Willebrand Factor (vWF) antigen in patients with coronavirus disease 2019 (COVID-19) with a poor outcome compared with those with a good outcome, and explored factors that may affect the difference in terms of vWF antigen between the two groups. Methods A comprehensive literature search of PubMed, Embase and Scopus databases was undertaken from inception until 7 April 2021. The primary outcome was poor outcome, which is a composite of mortality and severity of COVID-19. Results Ten studies including a total of 996 patients were included in this systematic review and meta-analysis. vWF antigen was higher in patients with poor outcomes [standardized mean difference (SMD) 0.84 [0.45–1.23], P <0.001; I 2 =87.3, P <0.001). For subgroup analysis on studies that reported the vWF antigen level as a percentage, the mean difference was 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 the platelet count (coefficient 0.0061, P =0.001), d-dimer level (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) or malignancy (coefficient 0.0487, P =0.608). Conclusion This meta-analysis showed that the level of vWF antigen was significantly higher in patients with COVID-19 with a poor outcome, signalling marked endotheliopathy. Meta-regression showed that the differences became larger as the platelet count, d-dimer level and factor VIII level increased.