TOPLINE:

In a cohort of US adults with West Nile virus infection, multiple comorbidities — including chronic kidney disease, cerebrovascular disease, hematologic malignancies, and multiple sclerosis — and older age were associated with a higher risk for West Nile neuroinvasive disease (WNND). Those who developed WNND had a nearly 2.5-fold higher risk for 30-day mortality.

METHODOLOGY:

• In this retrospective cohort study, researchers identified risk factors for WNND and mortality among US adults with West Nile virus infection between 2013 and 2024 using the TriNetX Research Network database.
• Overall, 3064 patients had West Nile virus infection; demographic data were available for 1127 patients with WNND (mean age at diagnosis, 59 years; 61% men) and 1249 patients with West Nile fever (mean age at diagnosis, 55 years; 48% men).
• Potential risk factors were assessed if documented within 30 days before or on the date of West Nile virus diagnosis.
• The primary outcomes were the development of WNND and all-cause mortality.

TAKEAWAY:

• The risk for WNND was significantly higher with older age (adjusted hazard ratio [aHR], 1.10 per decade), male sex (aHR, 1.29), chronic kidney disease (aHR, 1.21), cerebrovascular disease (aHR,1.22), hematologic malignancies (aHR, 1.38), immunosuppressant use (aHR, 1.43), hypertension (aHR, 1.18), alcohol-related disorders (aHR, 1.54), and multiple sclerosis (aHR, 2.34; P < .05 for all).
• Overall, 13% of patients died, with 33% of deaths occurring within 30 days of diagnosis; the overall case fatality rate for WNND in this cohort was 16%.
• Within 30 days of diagnosis, the risk for all-cause mortality was significantly higher with WNND (aHR, 2.49), older age (aHR, 1.32 per decade), heart diseases other than ischemic disease (aHR, 5.50), chronic kidney disease (aHR, 2.08), and cerebrovascular disease (aHR, 2.00; P < .05 for all).
• The associations of mortality with WNND, age, chronic kidney disease, and cerebrovascular disease were consistent at 30 days, 90 days, and overall, whereas the association with heart diseases other than ischemic disease was significantly stronger within 30 days.

IN PRACTICE:

“This risk, coupled with the increasing prevalence of multiple risk factors associated with WNND (such as age, immunocompromise, hypertension, heart disease, CEVD [cerebrovascular disease], and CKD [chronic kidney disease]), indicates that a growing population in the US may be at risk for morbidity and mortality following WNV [West Nile virus] infection,” the authors wrote.

SOURCE:

The study was led by Seth D. Judson, MD, MHS, David Geffen School of Medicine, University of California, Los Angeles. It was published online on December 10, 2025, in JAMA Network Open.

LIMITATIONS:

The analysis relied on diagnostic codes, which could have misclassified cases and affected risk estimates. The TriNetX platform did not allow checks for collinearity, clustering by site, or time-varying effects, potentially making variance estimates too narrow. Because most data came from academic and acute care settings, the findings may have limited generalizability to lower-acuity clinical settings.

DISCLOSURES:

The study was supported by the National Institutes of Health and by the Sherrilyn and Ken Fisher Center for Environmental Infectious Diseases, Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore. The authors reported having no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.