Von Willebrand Factor and ADAMTS-13 Are Associated with the Severity of COVID-19 Disease

Abstract

Coagulopathy in COVID-19 patients is presumably based on systemic hypercoagulation with the inflammatory response. As a result of endothelial dysfunction, tissue factor and von Willebrand factor (vWF) are released into the blood stream, which leads to prothrombinase activation. The vWF/ADAMTS-13 ratio can be used for monitoring the severity of the disease. This observational prospective study included 141 patients with COVID-19. In patients with mild COVID-19 (group 1), the assessment was performed on the 3rd–7th day of illness (point 1) and 14–28 days after recovery (point 2). In patients with moderate (groups 2) and severe (group 3) COVID-19, the assessment was performed during hospitalization (point 1) and after 14 days (point 2). The vWF:RCo/ADAMTS-13:activity (point 1), vWF/ADAMTS-13 (point 2) and vWF:RCo/ADAMTS-13:activity (point 2) ratios were significantly higher in patients with moderate and severe COVID-19. Moreover, in these patients, both ratios increased after recovery (point 2), which is a negative prognostic factor of thrombotic complications. Thus, COVID-19 is characterized by a decrease in the concentration and activity of ADAMTS-13 metalloproteinase, especially in patients with the severe form of COVID-19. A decrease in ADAMTS-13 activity results in an increase in vWF concentration and activity so the ratio of vWF to ADAMTS-13 changes significantly.

Biomarkers of endothelial dysfunction are associated with poor outcome in COVID‐19 patients: A systematic review and meta‐analysis

“…84 Indeed, numerous studies have reported elevated levels of vWF in COVID-19 patients. [28][29][30][32][33][34] On the other hand, decreased levels of ADAMTS13 has been detected in these patients, 31,47,48 and ratio of vWF antigen to ADAMTS13 activity is reportedly elevated in them. 6,49 Joly et al highlighted that increased vWF antigen to ADAMTS13 activity ratio is correlated with mortality, 34 while Mancini et al reported that imbalance between vWF antigen and ADAMTS13 activity is associated with disease severity.…”

“…We reviewed 7 studies 10,31,34,40,46–48 examining the serum levels of ADAMTS13 antigen among 651 patients (136 with poor outcome and 515 with good outcome). The pooled standard mean difference between the two groups was −0.69 (−0.90, −0.47) ( p < 0.00001), indicating the decreased ADAMTS13 antigen levels in critically ill patients (Figure 2, panel C).…”

“…We reviewed 7 studies 10,31,34,40,[46][47][48] indicating the decreased ADAMTS13 antigen levels in critically ill patients (Figure 2, panel C). The heterogeneity between studies was low (I 2 = 0%, p = 0.73).…”

“…The heterogeneity between studies was low (I 2 = 0%, p = 0.73). Regarding ADAMTS13 activity, we analysed 10 studies 6,28,30,34,38,39,42,43,47,49 that assessed 736 patients, 318…”

“…ADAMTS13 activity also showed a significant decline in patients with poor outcome (SMD: −0.84 (−1.06, −0.61), p < 0.00001) (Figure 2, panel B) and the heterogeneity between studies was low (I 2 = 43%, p = 0.07). Three outlier studies 38,43,47 were excluded resulting in considerable reduction of heterogeneity among studies (I 2 = 0%, p = 0.52), however, the overall effect size remained significant (SMD: −1.03 (−1.25, −0.81), p < 0.00001).…”