The Role of Von Willebrand Factor in the Pathogenesis of Pulmonary Vascular Thrombosis in COVID-19

Abstract

The increased plasma levels of von Willebrand factor (VWF) in patients with COVID-19 was reported in many studies, and its correlation with disease severity and mortality suggest its important role in the pathogenesis of thrombosis in COVID-19. We performed histological and immunohistochemical studies of the lungs of 29 patients who died from COVID-19. We found a significant increase in the intensity of immunohistochemical reaction for VWF in the pulmonary vascular endothelium when the disease duration was more than 10 days. In the patients who had thrombotic complications, the VWF immunostaining in the pulmonary vascular endothelium was significantly more intense than in nonsurvivors without thrombotic complications. Duration of disease and thrombotic complications were found to be independent predictors of increased VWF immunostaining in the endothelium of pulmonary vessels. We also revealed that bacterial pneumonia was associated with increased VWF staining intensity in pulmonary arterial, arteriolar, and venular endothelium, while lung ventilation was an independent predictor of increased VWF immunostaining in arterial endothelium. The results of the study demonstrated an important role of endothelial VWF in the pathogenesis of thrombus formation in COVID-19.

Plasma Proteomics Unveil Novel Immune Signatures and Biomarkers upon SARS-CoV-2 Infection

“…Moreover, extracellular matrix proteins were found to be upregulated in patients with COVID-19 that indicates the potential tissue damage and remodeling due to a SARS-CoV-2 infection such as the pro-inflammatory TNC [ 88 ], COL6A3, MATN2 and THBS4/TSP4, which are involved in tissue regeneration and wound healing [ 89 ], not previously found in patients with COVID-19. In agreement with previous findings, the Von Willebrand factor (VWF) was upregulated in patients with COVID-19 which can contribute to their hypercoagulable state and increased venous thromboembolism rate [ 90 , 91 ].…”

Targeting IL-6 trans-signalling by sgp130Fc attenuates severity in SARS-CoV-2 -infected mice and reduces endotheliopathy

“…6 a). Other endothelial cell activation markers described in COVID-19, including vWF and VCAM1, 49 , 50 were analysed. vWF expression was found in endothelium as well as in oedematous fluid and thrombi.…”

Spatiotemporal analysis of SARS-CoV-2 infection reveals an expansive wave of monocyte-derived macrophages associated with vascular damage and virus clearance in hamster lungs

“…The increased vascular hyperpermeability contributes to severe COVID-19 [37]. vWF and other coagulation factors play a central role in platelet adhesion to damaged vascular subendothelium and cloth formation [46], and their role in thrombosis in COVID-19 was recently shown [47]. Upregulation of coagulation factors associated with endothelial injury suggests that such areas may serve as leaky entry points for MDM.…”