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

Abstract

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.

Dipeptidyl peptidase-4 (DPP-IV) inhibitor was associated with mortality reduction in COVID-19 — A systematic review and meta-analysis

“…The finding of lower soluble DPP-IV receptor in COVID-19 in compare to healthy subject might also indicates the role of DPP-IV in facilitating viral entry although the exact interactions between DPP-IV and coronavirus and how it influence the viral entry has not been established [ [59] , [60] , [61] ]. However, since poor glucose control, cytokine storm, and multiorgan dysfunction have been established as a risk factor for worse outcome [ 40 , [62] , [63] , [64] , [65] , [66] , [67] , [68] , [69] , [70] , [71] , [72] , [73] , [74] ], one might consider the benefit of excellent glucose control, cardiorenal effect and inflammatory modulation of DPP-IV inhibitor as an potential drug in treating T2DM patient with COVID-19 [ 5 , 75 ].…”

COVID-19 and Cardiovascular Complications: An Updated Review

“…The induction of hypoxia-induced factors and endothelial inflammation during hypoxia and systemic inflammatory response may contribute to the formation of microthrombi [29]. Coagulopathy is one of the hallmarks of COVID-19, there is an alteration in several important parameters of platelet and coagulation function such as von Willebrand factor, d-dimer, and thromboplastin time [34], [35], [39], [42], [43]. Coagulopathy is hypothesized to be one of the most important complications, leading to mortality in patients with COVID-19 [39].…”

“…In a retrospective cohort study from China, elevated D-dimer was associated with poor prognosis and a higher risk of mortality [28]. Metaanalysis showed that changes in von Willebrand factor level, d-dimer, and thromboplastin time were strongly associated with mortality in patients with COVID-19 [34], [35], [39], [42], [43].…”

Viral-Induced Inflammatory Coagulation Disorders: Preparing for Another Epidemic

“…Internalization of angiotensin-converting enzyme 2 (ACE2) to increase angiotensin II levels causes vasoconstriction, hyperinflammation, and the release of prothrombotic substances such as von Willebrand factor (VWF), P-selectin, factor VIII, and angiopoietin 2. 17 18 These factors are all involved in the pathogenesis of thrombogenicity in COVID-19. 19 In CAC, bleeding can occur, especially in advanced stages of critically ill patients.…”