Objective:

To describe West Nile virus (WNV) epidemiology and report a series of four fatal neuroinvasive cases.

Background:

WNV is the leading cause of arboviral neuroinvasive disease in the United States. Cook County, Illinois ranks among the top WNV-burdened areas, contributing 6.3% of all CDC-reported neuroinvasive cases from 1999–2022. Seroprevalence data suggest that fewer than 1% of infections become neuroinvasive, yet these cases dominate surveillance; true infection rates are 50–100× higher than reported. Most cases occur in persons aged ≥50 years and peak in late summer, when WNV amplifies in a bird–mosquito–bird cycle involving passerines (crows, robins, & jays). Neuroinvasive WNV mortality approaches 9%, with nearly half of cases requiring ICU admission. No official guidelines exist for WNV in immunocompromised patients; management relies on vector avoidance and supportive therapy in severe infection.

Design/Methods:

We reviewed publicly available surveillance data from the CDC ArboNET Surveillance System and Cook County Department of Public Health. Four cases are detailed as follows:

Results:

Four patients (ages 69–87; 3 male, 1 female) with CSF WNV IgM positivity were cared for in a tertiary hospital ICU setting in September, 2025. Two patients were immunocompromised secondary to malignancy with chemotherapy or lung transplant. Approximately one week of nonspecific flu-like symptoms preceded presentation before all patients became acutely encephalopathic, requiring intubation and mechanical ventilation for airway protection. Neuroimaging findings included bilateral thalamic hyperintensities on MRI. Three developed worsening leukopenia with secondary pulmonary and bloodstream infections, two with fungemia, requiring broad-spectrum empiric treatment. Two received IVIG without significant clinical benefit. All died during hospitalization (mean, 20 days).

Conclusions:

WNV has high mortality in elderly and immunocompromised patients who commonly reside in urban high-risk centers like Chicago. IVIG has been used anecdotally but lacks proven efficacy in the treatment of neuroinvasive WNV. Prevention of WNV through public and provider awareness and robust vector control remains paramount.