Correlation of clinical, biochemical and molecular profile of dengue with disease severity.

Purpose: The Indian subcontinent is endemic to dengue, with an estimated 33 million clinically apparent dengue cases annually, contributing to one-third of the total global dengue burden. This study aimed to assess the disease burden among dengue-suspected patients visiting our tertiary care center in North India and to explore the correlation between clinical-biochemical parameters in dengue fever or severe dengue with disease severity. Methods: A total of 318 dengue patients were enrolled in dengue fever with/without warning signs (DF ± WS, n = 229) and severe dengue (SD, n = 89) cohorts. Demographical, clinical, and biochemical data were collected during recruitment. Blood samples were screened for dengue NS1 antigen and IgM antibodies using ELISA. Representative NS1 antigen-positive samples (n = 50) were further tested for dengue RNA and serotyping via reverse transcriptase RT-PCR, followed by phylogenetic analysis of 17 PCR-positive samples. Results: The mean age was 36.02 ± 14.73 years and 35.46 ± 13.61 years for DF ± WS and SD individuals, respectively. Among DF ± WS patients, 49 (21.4%) were NS1 antigen positive, 122 (53.28%) had dengue IgM, and 58 (25.32%) were positive for both. In the severe dengue cohort, 14 (15.73%) and 45 (50.56%) were positive for NS1 and IgM, respectively, with 30 (33.71%) patients positive for both NS1 antigen and IgM antibodies. Among the DF ± WS and SD cohort, 35/229 (15.29%) and 31/79 (39.25%) patients had IgG antibodies depicting secondary dengue. The majority of patients were from Chandigarh (n = 130), followed by Punjab (n = 85) and Haryana (n = 46). With approximately six days of illness at the time of enrolment, fever, joint pain, lethargy, vomiting, hematocrit, and rashes were present in more than 50% of cases in DF ± WS and SD patients. Severe dengue patients exhibited significant thrombocytopenia (88,340 ± 6,575/ml vs. 40,620 ± 5,280/ml) and elevated liver enzymes compared to DF ± WS (AST: 1506 ± 220.4 IU/L vs. 179.3 ± 16.79 IU/L; ALT: 906.8 ± 141.4 IU/L vs. 124.8 ± 10.17 IU/L; ALP: 169.3 ± 20.06 IU/L vs. 120.4 ± 7.14 IU/L). Among SD patients, 20 deaths (22.47%) were reported, primarily due to multiple organ dysfunction syndrome (MODS), while only two deaths occurred in the DF ± WS cohort for unrelated reasons. Sequencing revealed 14 and 3 isolates belonging to serotype-2 and serotype-4, respectively. Conclusion: Elevated liver function tests and severe thrombocytopenia in dengue patients indicate progression towards severe dengue with high mortality. A notable prevalence of secondary dengue infection (39.25%) was found in severe cases, with serotype-2 predominating in the north-Indian population. Supplementary Information: The online version contains supplementary material available at 10.1007/s13337-025-00930-0.