Neutrophil kinetics in dengue patients compared to other febrile illnesses: results from 6082 patients in Vietnam

Background Neutrophils are implicated in dengue pathogenesis, yet their kinetics and association with clinical outcomes remain poorly characterized. We investigated neutrophil count trajectories and their relationship with disease severity using a large, pooled dataset from clinical studies conducted over 20 years in Vietnam. Methods This analysis included data from 11,290 patients across nine studies (1999–2018). Patients were enrolled in outpatient settings (54.2%), at hospital admission (28.9%), or in intensive care units (16.9%). Clinical and laboratory parameters were recorded daily. Dengue was laboratory-confirmed via RT-PCR, NS1, or IgM seroconversion. Dengue shock syndrome (DSS) was defined according to WHO 1997 and 2009 criteria. Linear mixed-effects models were employed to characterize the kinetics of total white cell, neutrophil, and lymphocyte counts. Results Among 6,082 patients with available neutrophil data, 4,071 had confirmed dengue (including 1,067 [26%] with DSS) and 2,011 had other febrile illnesses (OFI). Neutrophil and total white cell counts declined during the febrile phase, reaching a nadir on illness days 4–6. This trajectory differed significantly from lymphocytes, which reached a nadir earlier, on days 2–3. Transient neutropenia (< 1.5 K/µL) was more prevalent in uncomplicated dengue (84%) than in DSS (47%) or OFI (33%). Conclusions Transient neutropenia is a hallmark of dengue infection, particularly in uncomplicated cases. Neutrophils follow a distinct kinetic profile compared to lymphocytes, with a significantly later nadir. These findings suggest that neutrophil dynamics are closely linked to the clinical course of dengue and warrant further mechanistic research to clarify their role in pathogenesis and recovery.