Von Willebrand factor collagen-binding capacity predicts in-hospital mortality in COVID-19 patients: insight from VWF/ADAMTS13 ratio imbalance.

ABSTRACT

BACKGROUND: Microthrombosis is a hallmark of COVID-19. We previously described von willebrand factor (VWF) and their high molecular weight multimers (HMWMs) as potential trigger of microthrombosis. OBJECTIVES: Investigate VWF activity with collagen-binding assay and ADAMTS13 in COVID-19. METHODS AND RESULTS: Our study enrolled 77 hospitalized COVID-19 patients including 37 suffering from a non-critical form and 40 with critical form. Plasma levels of VWF collagen-binding ability (VWFCB) and ADAMTS13 activity (ADAMTS13Act) were measured in the first 48 hours following admission. VWFCB was increased in critical (631% IQR [460-704]) patients compared to non-critical patients (259% [235-330], p < 0.005). VWFCB was significantly associated (r = 0.564, p < 0.001) with HMWMs. Moreover, median ADAMTS13Act was lower in critical (64.8 IU/dL IQR 50.0-77.7) than non-critical patients (85.0 IU/dL IQR 75.8-94.7, p < 0.001), even if no patients displayed majors deficits. VWFAg-to-ADAMTS13Act ratio was highly associated with VWFCB (r = 0.916, p < 0.001). Moreover, VWFCB level was highly predictive of COVID-19 in-hospital mortality as shown by the ROC curve analysis (AUC = 0.92, p < 0.0001) in which we identified a VWFCB cut-off of 446% as providing the best predictor sensitivity-specificity balance. We confirmed this cut-off thanks to a Kaplan-Meier estimator analysis (log-rank p < 0.001) and a Cox-proportional Hazard model (HR = 49.1, 95% CI 1.81-1328.2, p = 0.021) adjusted on, BMI, C-reactive protein, and D-dimer levels. CONCLUSION: VWFCB levels could summarize both VWF increased levels and hyper-reactivity subsequent to ADAMTS13 overflow and, therefore, be a valuable and easy to perform clinical biomarker of microthrombosis and COVID-19 severity.