Utility of blood biomarkers in inpatients with West Nile virus infection: an exploratory study

Background: West Nile virus (WNV) infection is an emerging public health concern in Southern Europe and may present with heterogeneous clinical phenotypes, ranging from predominantly neurologic manifestations to systemic inflammatory and septic presentations. While lymphocytopenia and immune dysregulation are well-recognized features of WNV infection, data on routine hematological parameters and composite inflammatory indices, and their potential association with different clinical presentations, remain limited. Methods: We retrospectively analyzed a multicenter Italian cohort of 30 consecutive inpatients with confirmed neuroinvasive WNV infection. Patients were classified according to their predominant clinical presentation at admission as neurologic or septic phenotype. Baseline clinical characteristics, routine hematological parameters, routine hemostasis tests and composite inflammatory indices were collected. Between-group comparisons were performed using non-parametric tests. Univariable logistic regression was used to screen for laboratory variables associated with the septic phenotype, and a parsimonious multivariable model including only significant predictors was then fitted. Results: Seventeen patients (56.7%) presented with a predominantly neurologic phenotype and 13 (43.3%) with a septic phenotype. Median age was 77 years, and baseline comorbidities were broadly similar between groups. Both phenotypes showed marked systemic inflammation, lymphocytopenia and elevated composite inflammatory indices. Patients with a septic presentation displayed numerically higher neutrophil-to-lymphocyte ratio, systemic immune-inflammation index and platelet-related inflammatory indices, although these differences did not reach statistical significance. In univariable logistic regression analyses, lower mean corpuscular hemoglobin (MCH) and lower monocyte percentage were significantly associated with the septic phenotype. In a parsimonious multivariable model, lower MCH remained independently associated with septic presentation (OR 0.41, 95% CI 0.18-0.95), whereas monocyte percentage showed a non-significant trend. Conclusion: In this exploratory cohort of patients with neuroinvasive WNV infection, subtle alterations in erythrocyte indices and monocyte counts were associated with a septic clinical presentation, whereas inflammatory indices showed only non-significant trends. These findings suggest that routine hematological parameters may contribute to the early phenotypic characterization of WNV infection. Larger, multicenter studies are warranted to confirm these observations and to clarify the prognostic value of routine hematological and inflammation-related biomarkers in this setting.