Biomarkers of thromboinflammation correlate to COVID-19 infection and admission status in emergency department patients

ABSTRACT

Background COVID-19-associated coagulopathy is incompletely understood. Objectives To characterize thrombin generation, Von Willebrand Factor (VWF), neutrophil extracellular traps (NETs), and their role in COVID-19 risk stratification in the emergency department (ED). Patients/methods Plasma samples from 67 ED COVID-19 patients were compared to 38 healthy volunteers (HVs). Thrombin generation (calibrated automated thrombogram, CAT) was expressed as lag time (LT, min), peak height (PH, min), and time to peak (ttPeak, min). Citrullinated nucleosomes and histones were quantified with ELISA, VWF antigen and activity (IU/dL) through latex immunoassay, Factor VIII (IU/dL) through one-stage optical clot detection, and VWF multimers with western blot densitometry. Wilcoxon testing and multivariable logistic regression were performed. Results presented as median [Q1, Q3];p < 0.05 significant. Results COVID-19 patients had longer LT (4.00 [3.26, 4.67];2.95 [2.67, 3.10], p < 0.001) and ttPeak (7.33 [6.33, 8.04];6.45 [6.00, 7.50], p = 0.004), greater VWF antigen (212 [158, 275];110 [91, 128], p < 0.001) and Factor VIII levels (148 [106, 190];106 [86, 129], p < 0.001), with decreased high molecular weight multimers (Normalized multimer ratio 0.807 [0.759, 0.869];0.891 [0.858, 0.966], p < 0.001), than HVs. COVID-19 patients requiring admission from the ED had longer LT and ttPeak with greater VWF antigen and Factor VIII levels than those not admitted. Two and three variable models of CAT parameters and VWF correlated with COVID-19 and admission status (C-statistics 0.677 to 0.922). Conclusions Thrombin generation kinetics and VWF levels, independent of NETs, may have a role in predicting admission need for COVID-19 patients.