Association of intermediate monocytes with dengue severity among the pediatric population of Odisha, India

Dengue virus (DENV) infection in children exhibits varied clinical presentations, wherein the role of monocytes is important in the innate immune response. In this study, laboratory-confirmed DENV pediatric patients (n = 120), with DENV-2 infection, were categorized into dengue fever (DF), dengue with warning signs (DWS) and severe dengue (SD) were assessed for monocyte subpopulation analysis using immunophenotyping involving CD14 and CD16 host-surface markers. Molecular docking was performed using HADDOCK 2.4 to analyze the interactions between CD14, CD16 and DENV envelope and capsid proteins. Among the cases, 84 (70%) were classified as DF and 36 (30%) as DWS & SD. Hematological and biochemical parameters indicated that thrombocytopenia and elevated hematocrit (> 40%) were significantly more common in DWS & SD, with markedly elevated liver enzymes (ALT and AST) in severe cases. Classical monocytes (CM-CD14++ CD16-) constituted 72.51% and 66.25% of the monocyte population in DF and DWS & SD cases, respectively. Intermediate monocytes (IM-CD14+ CD16+) comprised 9.89% and 30.86% in DF and DWS & SD cases, respectively. Non-classical monocytes (NCM-CD14+ CD16++) comprised 5.75% and 8.12% in DWS & SD and DF cases, respectively. In silico analysis revealed host CD16 and CD14 exhibited potential interactions with DENV capsid and envelope proteins, with binding energies - 8.9, - 10.1, - 8.6, and - 11.1 kcal/mol, respectively. IM was significantly increased in DWS & SD compared to DF (p < 0.05). These findings suggest that IM could act as host markers of DENV severity in children.