Dengue virus non-structural protein 1 binding to thrombin as a dengue severity marker: Comprehensive patient analysis in south Taiwan

Background: Previously we identified a complex of non-structural protein (NS) 1 – Thrombin (NST) in dengue infected patients. Here, we investigated how the concentration of NS1 and NST differ in various dengue severity levels as well as their demographic and clinical features. Several comorbid (hypertension, diabetes, and chronic renal failure) often found in dengue patients were also measured and analyzed. Methods: A total of 86 dengue patients (52 not severe and 34 severe), were enrolled and had their blood taken. Blood samples were further verified for clinical blood parameters, including liver and renal function tests and serologic assays (NS1 and NST). Patients' severity was grouped based on WHO 2009 classification, which separates patients into dengue without warning signs (DNWS), dengue with warning signs (DWWS), and severe dengue (SD). DWWS is explained as DNWS with warning signs (persistent abdominal pain, persistent vomiting, liver enlargement, bleeding (any kind), fatigue, and restlessness). SD are those with severe plasma leakage, severe bleeding, or severe organ impairment. Multivariate regression analysis was used to predict the role of NST on the dengue severity development and receiver operating characteristic (AUROC) test was utilized to evaluate separability. Results: The analysis revealed that NS1 significantly impacts the disease outcome (p 0.018, OR = 2.467 (1.171–5.197)) but not beyond the effect through NST (p 0.108, OR = 0.085 (0.004–1.719)). We also prove that NST was a better severity biomarker compared to NS1, as it can predict progression from DNWS to DWWS (AUC: NS1 = 0.771∗∗, NST = 0.81∗∗) and SD (AUC: NS1 = 0.607, NST = 0.754∗) significantly. Conclusions: This finding suggests the importance of NST in mediating the NS1 effect to promote dengue severity progression and its promising capability as an acute stage dengue severity biomarker.