Contribution of Hematological, Biochemical, and Inflammatory Factors in Temporal Variation of Disease Severity Among Eastern Indian Dengue Patients

India, being dengue (DENV) endemic country, faces recurrent outbreaks. Favorable environmental conditions for dengue in eastern India also enhanced patient mortality during 2019–2024. The current study was performed to understand the effect of DENV secondary infection, hematological and biochemical parameters, serotypic shift, and viral load on disease severity. DENV was screened among 1169 symptomatic patients by qRT-PCR, NS1-antigen, anti-dengue-IgM, IgG-ELISA, and categorized according to WHO classification during 2020–2023. DENV-titer, serotype was determined by qRT-PCR. Statistical analysis was performed using GraphPad Prism 9 software. Among total 663 dengue + patients, 42.23%, 55.5%, 51.88%, 41.78% were confirmed by DENV-NS1-antigen, anti-dengue-IgM and IgG-antibody ELISA, qRT-PCR, respectively. Markedly increased prevalence of severe dengue symptoms, namely thrombocytopenia, hemorrhage, ascites, and liver enlargement, was observed during 2021–2022 and among secondary dengue patients. Severe dengue patients were mostly detected by IgM+, IgM+PCR+, NS1+IgG+PCR+, and NS1+IgM+IgG+PCR+ marker combinations. DENV3 and DENV2 + 3 serotypes were most prevalent during 2021–2022. Moreover, significantly decreased count of WBC, RBC, MCHC, platelet, albumin, HDL, LDL; increased amount of hemoglobin, HCT, ALT, ALP, urea, and AST/ALT was observed among patients of 2021–2022 and those with thrombocytopenia, hemorrhage, ascites and liver enlargement (p value < 0.0001–0.0282). Significantly higher concentration of IL-6 and IL-8 among those with high viral load, secondary dengue infection, and disease severity also substantiated this finding (p value = 0.0104–0.0464). Thus, the present study provided evidence for the role of co-infecting serotypes, hematological, biochemical, and pro-inflammatory factors on year-wise complexity of dengue severity among eastern Indian patients.