Clinical and immunometabolic profiles of overweight and obese patients with dengue: A matched cohort study

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Abstract Background Obesity is a risk factor for severe dengue, but underlying mechanisms remain unclear. This study compared clinical features, outcomes, and biomarkers between overweight/obese and healthy-weight patients with dengue infection. Methods We conducted an observational matched cohort study (2019-2022) including 75 overweight/obese patients and 75 matched healthy-weight patients with dengue (by age, sex, illness phase, and inpatient ward). The primary clinical outcome was overall severity per WHO 2009 classification. Secondary outcomes included warning signs, ICU admission, fever clearance, and hospital stay. Laboratory outcomes comprised trajectories of hematology, biochemistry, and endothelial, inflammatory, and lipid biomarkers. Results The majority of patients were enrolled on day 2-3 of illness, with DENV-2 (63.3%) as the predominant serotype and secondary infections in 93.4%. Clinical signs and symptoms at enrolment and severe dengue development (6.3% vs. 9.2%) were comparable between groups. However, the overweight/obese group developed fluid accumulation more frequently (64.1% vs. 41.5%). Laboratory profiles showed consistently higher leukocyte (∼0.55-1 K/μL), neutrophil (∼0.19-0.84 K/μL), and lymphocyte counts (∼0.04-0.28 K/μL), total cholesterol (∼0.39-0.46 mmol/L), low-density lipoprotein cholesterol (∼0.36-0.48 mmol/L), triglycerides (∼0.21-0.44 log2-mmol/L), C-reactive protein (∼0.21-0.43 log10-mg/L), ferritin (∼0.12-0.15 log10-ng/mL), and leptin (∼0.89-1 log10-ng/mL) in the overweight/obese group, alongside lower high-density lipoprotein cholesterol (∼0.06-0.23 mmol/L) and adiponectin (∼0.05-0.24 log10-ng/mL). Liver transaminases were initially higher (days 1-5) in the overweight/obese group. Conclusions Overweight/obese patients with dengue infection display distinct clinical and immunometabolic profiles, particularly greater fluid accumulation, higher inflammatory markers and liver injury. These findings suggest obesity modifies the host response to dengue, and this patient group should be prioritized for upcoming immunomodulatory and other host-directed therapeutic trials. Author summary Dengue is a major global health problem, and people with obesity appear to have a higher risk of developing severe disease. However, the reasons for this increased vulnerability are still poorly understood. In this study, we compared 75 overweight or obese patients with dengue to 75 patients of healthy weight who were carefully matched by age, sex, disease stage, and hospital ward. Although both groups had similar symptoms at enrollment and similar rates of severe dengue, the overweight/obese group developed fluid accumulation more often-a key sign of clinical deterioration. They also showed distinct laboratory patterns throughout their illness. Overweight/obese patients consistently had higher levels of white blood cells, inflammatory markers, liver enzymes, and lipid measures, as well as higher leptin and lower adiponectin, two hormones linked to metabolic health. These findings suggest that excess body weight alters the body’s immune and metabolic response to dengue infection, even when outward symptoms appear comparable. Understanding these differences is important because it can help clinicians identify patients at higher risk and guide the development of new treatments. Our results support prioritizing overweight and obese individuals for future trials of immunomodulatory or other host-directed therapies for dengue.

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