West Nile Neuroinvasive Disease: Epidemiology, Risk Factors, Neurological Outcomes, and the Role of Corticosteroid and Immunoglobulin Therapy

Background: West Nile virus (WNV) infection is an emerging arboviral disease with increasing relevance in Northern Italy. Although most infections are asymptomatic or mildly symptomatic, WNV may cause neuroinvasive disease, neurological sequelae, and death. Evidence regarding prognostic factors and the clinical role of corticosteroid and intravenous immunoglobulin therapy remains limited. Methods: Epidemiological data on WNV cases reported in the province of Modena from 2015 to 2025 were obtained from the local Public Health Service. Then, a retrospective single-center study was conducted, including patients diagnosed with WNV infection at the University Hospital of Modena between 2013 and 2024. Patients were identified through hospital discharge diagnoses and included after manual review of electronic medical records. Demographic, clinical, laboratory, microbiological, neuroradiological, therapeutic, and composite outcome (the presence of one or more outcomes between exitus and neurological sequelae) data were collected in a dedicated database and analysed using STATA. Results: In the provincial epidemiological analysis, 238 WNV cases were reported between 2015 and 2025, with two major peaks in 2018 and 2024. 173 patients were hospitalized, whereas 60 patients were managed at home. A total of 77 patients with confirmed WNV infection were studied as inpatient. Mean age was 68.34 years and 47 patients (61.04%) were male. Meningoencephalitis was the most frequent clinical form, occurring in 57 patients (74.03%), while 20 patients (25.97%) presented with West Nile fever. Overall mortality was 25.97%, and 30-day mortality occurred in 7 patients (9.09%). Neurological sequelae were reported in 30.56%. In univariate logistic regression analysis, factors associated with composite outcomes were: hypertension (OR 3.10, 95% CI 1.17–8.15, p = 0.022), positive MRI findings (OR 4.37, 95% CI 1.23–15.48, p = 0.022), ICU admission (p = 0.037). Steroid therapy didn’t show any significant ipact on outcome. Steroid was more frequently prescribed in patients with confusion at disease onset (p= 0.039) and with more comorbidites (p= 0.048). Conclusions: West Nile virus infection still represents a relevant public health issue in the province of Modena, particularly during the summer seasons of specific epidemic years. In this cohort, WNV infection was associated with a substantial clinical burden, including mortality and neurological sequelae. Corticosteroid therapy was not associated with a clear improvement in clinical outcomes; rather, it appeared to be administered more frequently to patients with a higher comorbidity burden and more severe clinical presentation. These findings suggest that steroid use likely reflected disease severity rather than an independent predictor of better outcome.