Antioxidant Response as a Candidate Prognostic Factor for Dengue Hypotensive and Hemorrhagic Complications: Results from a Nested Case-Control Study in Colombia

Dengue infection has been associated with oxidative stress (OS) induction; however, whether such a response predicts the development of complications remains unknown. We conducted a case-control study (1:2 ratio) nested within a cohort of febrile patients with a presumptive or confirmed diagnosis of dengue. Incident cases were patients who developed hypotension or severe bleeding during the follow-up, whereas controls did not. Total antioxidant status (TAS), superoxide dismutase (SOD), and glutathione peroxidase activity (GPx) were quantified in serums obtained ≤96 h from disease onset. The association between each biomarker and complications was evaluated by estimating adjusted odds ratios (ORs) using logistic regression. We evaluated 132 patients (median age: 19.0 years; 58.2% males). TAS and SOD were higher among cases than controls (2.1 versus 1.7 mM and 6.7 versus 6.0 U/mL, respectively), and the opposite was observed for GPx (128.1 versus 133.7 mmol/min/mL); however, none of these contrasts reached statistical significance. In the multivariate analysis, higher levels of TAS and SOD were associated with a higher likelihood of complications up to 3.5 mM (OR = 2.46; 95%CI: 1.10–5.53) and 8.0 U/mL (OR = 1.69; 95%CI: 1.01–2.83), respectively. GPx did not show an association with hypotension or severe bleeding. Our results suggest that the induction of OS during the acute phase of dengue infection might be a prognostic factor of hypotensive and hemorrhagic complications.