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

• Published in: International journal of infectious diseases Vol. 117; pp. 267 - 273
• Main Authors: Wibowo, Arief, Pranata, Raymond, Lim, Michael Anthonius, Akbara, Mohammad Rizki, Martha, Januar Wibawa
• Format: Journal Article
• Language: English
• Published: Canada Elsevier Ltd 01-04-2022; The Authors. Published by Elsevier Ltd on behalf of International Society for Infectious Diseases; Elsevier
• Subjects: Coagulopathy; Coronavirus; COVID-19; Endothelial dysfunction; Humans; Mortality; Thrombosis; von Willebrand Factor; Endothelial dysfunction; Coronavirus; Thrombosis; Mortality; Coagulopathy
• ISSN: 1201-9712; 1878-3511
• DOI: 10.1016/j.ijid.2021.06.051

•Severe coronavirus disease 2019 was associated with marked endotheliopathy.•Von Willebrand factor antigen was higher in patients with a poor outcome.•The strength of association was affected by platelet count, d-dimer level and factor VIII level.
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.
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.
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; I2=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; I2=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).
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.