Von Willebrand factor propeptide in severe coronavirus disease 2019 (COVID-19): evidence of acute and sustained endothelial cell activation.

Abstract

Endothelial cell (EC) activation plays a key role in the pathogenesis of pulmonary microvascular occlusion, which is a hallmark of severe coronavirus disease 2019 (COVID-19). Consistent with EC activation, increased plasma von Willebrand factor antigen (VWF:Ag) levels have been reported in COVID-19. Importantly however, studies in other microangiopathies have shown that plasma VWF propeptide (VWFpp) is a more sensitive and specific measure of acute EC activation. In the present study, we further investigated the nature of EC activation in severe COVID-19. Markedly increased plasma VWF:Ag [median (interquatile range, IQR) 608·8 (531-830)iu/dl] and pro-coagulant factor VIII (FVIII) levels [median (IQR) 261·9 (170-315) iu/dl] were seen in patients with severe severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. Sequential testing showed that these elevated VWF-FVIII complex levels remained high for up to 3 weeks. Similarly, plasma VWFpp levels were also markedly elevated [median (IQR) 324·6 (267-524) iu/dl]. Interestingly however, the VWFpp/VWF:Ag ratio was reduced, demonstrating that decreased VWF clearance contributes to the elevated plasma VWF:Ag levels in severe COVID-19. Importantly, plasma VWFpp levels also correlated with clinical severity indices including the Sequential Organ Failure Assessment (SOFA) score, Sepsis-Induced Coagulopathy (SIC) score and the ratio of arterial oxygen partial pressure to fractional inspired oxygen (P/F ratio). Collectively, these findings support the hypothesis that sustained fulminant EC activation is occurring in severe COVID-19, and further suggest that VWFpp may have a role as a biomarker in this setting.

• Authors: Soracha E Ward, Gerard F Curley, Michelle Lavin, Helen Fogarty, Ellie Karampini, Natalie L McEvoy, Jennifer Clarke, Maria Boylan, Razi Alalqam, Amy P Worrall, Claire Kelly, Eoghan de Barra, Siobhan Glavey, Cliona Ni Cheallaigh, Colm Bergin, Ignacio Martin-Loeches, Liam Townsend, Patrick W Mallon, Jamie M O'Sullivan, James S O'Donnell, Irish COVID-19 Vasculopathy Study (ICVS) Investigators
• Journal: British journal of haematology (Br J Haematol) Vol. 192 Issue 4 Pg. 714-719 (02 2021) ISSN: 1365-2141 [Electronic] England
• PMID: 33326604 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2020 British Society for Haematology and John Wiley & Sons Ltd.

Chemical References

• Biomarkers
• Protein Precursors
• von Willebrand Factor

Topics

• Adult
• Aged
• Biomarkers (blood)
• COVID-19 (blood)
• Endothelial Cells (metabolism, pathology)
• Female
• Humans
• Male
• Middle Aged
• Protein Precursors (blood)
• SARS-CoV-2 (metabolism)
• Severity of Illness Index
• von Willebrand Factor (metabolism)