Clinical Spectrum and Exploratory Mortality Markers in Hospitalized Patients with Different Clinical Presentations of West Nile Virus Infection: A Multicenter Cohort from Southern Italy

Background and Objectives: West Nile virus (WNV) infection has a broad clinical spectrum ranging from asymptomatic or mild disease to severe neuroinvasive forms. Data on hospitalized patients with atypical or non-neurological presentations remain limited. Materials and Methods: We conducted a retrospective multicenter observational study including 30 patients with laboratory-confirmed WNV infection admitted to internal medicine wards during a seasonal outbreak in Southern Italy. Clinical characteristics, hematological parameters, and in-hospital outcomes were analyzed. Results: Median age was 77 years, and 53% of patients were male. Neurological involvement was observed in 50% of patients, whereas 37% presented with septic-like manifestations. Overall in-hospital mortality was 43%, and early mortality within 10 days occurred in 17%. Neurological involvement was significantly more frequent among non-survivors and was associated with increased in-hospital mortality. Higher monocyte percentages were associated with overall mortality, whereas eosinopenia, leukopenia, and thrombocytopenia were associated with early mortality in exploratory analyses. Conclusions: Hospitalized patients with WNV infection may present with heterogeneous clinical phenotypes extending beyond classical neuroinvasive disease. Neurological involvement appears to be the main clinical marker of adverse outcome, while selected hematological parameters may provide preliminary prognostic information. Given the limited sample size and retrospective design, these findings should be considered hypothesis-generating.