Secondary dengue virus infection is associated with endothelial activation and hypotension in an outpatient cohort from the Philippines.

BACKGROUND

Secondary dengue virus (DENV) infection is a known risk factor for severe clinical manifestations. Antibody-dependent enhancement of viral pathogenesis explains this phenomenon; however, the underlying mechanisms remain incompletely defined.

OBJECTIVES

To compare the frequency of hypotension, endothelial activation, systemic inflammation, and thrombocytopenia in patients with primary and secondary DENV infection.

METHODS

This was a cross-sectional study among children and young adults aged 1-26 years conducted at an outpatient clinic in the Philippines. Secondary infection was defined by the presence of detectable anti-DENV IgG antibodies at presentation. Clinical data and haematologic parameters were recorded. Plasma concentration of circulating markers of endothelial activation and inflammation were quantified by Luminex® assay.

RESULTS

Among 244 patients (median age 9 years, 40% female), 93 (38%) were IgG positive. Secondary infection was associated with a 2.2-fold increased odds (95% CI, 1.1-4.1) of hypotension compared to primary infection. Endothelial activation, quantified using a composite index of six endothelial markers (Ang1, Ang2, sTie2, sFlt1, sICAM1, and sEndoglin), was significantly higher in secondary infection (p < 0.001). Platelet counts were lower in secondary infection (170 × 109/L vs 230 × 109/L, p < 0.0001). IL-10 levels were elevated in secondary infection (76 pg/mL vs 33 pg/mL, p < 0.001). Systemic inflammation, quantified using a composite index of four plasma markers (TNF, CXCL8/IL-8, CXCL10/IP-10, PCT), correlated with endothelial activation (τ = 0.39, p < 0.001) and IL-10 (τ = 0.32, p < 0.0001).

CONCLUSION

Endothelial activation, IL-10-mediated immune dysregulation, and platelet depletion are associated with transient vascular hyperpermeability in secondary DENV infection.