West Nile virus (WNV) is a mosquito-borne flavivirus resulting in substantial morbidity and mortality for patients who develop neuroinvasive disease (encephalitis, meningitis, and/or myelitis). Anti-CD20 therapies are increasingly used for inflammatory diseases and malignancy, and may predispose patients to poor outcomes from WNND due to impaired humoral immunity. Diagnosis of WNND is challenging for patients on anti-CD20 therapies due to poor sensitivity of antibody testing in this population.  Given the near doubling year-over-year of WNND reported by CDC ArboNET in 2023, better understanding this patient population is critical, especially as use of B-cell depleting therapies expands.

Characterize diagnostic strategies and clinical outcomes for a cohort of anti-CD20 treated patients with West Nile virus neuroinvasive disease (WNND).

Retrospective chart review of patients in the UCHealth system who received anti-CD20 therapies and were diagnosed with WNND between 2008-2023.

23 patients (17 women, 6 men) were included with mean age 56 years (range 27-86 years). Indications for anti-CD20 therapy included multiple sclerosis (13), rheumatological disease (5), malignancy (3), anti-NMDAR encephalitis (1), and transplant rejection (1); mean duration of treatment was 45.4 months (range 1-127 months). All patients presented with meningoencephalitis. For patients with available data, 8/19 had hypogammaglobulinemia while 17/17 had CD19+ depletion. While CSF WNV-IgM was positive in only 3/20 tested patients, CSF WNV-RT-PCR was positive in 13/14. The remaining patients were identified based on serum WNV-IgM and RT-PCR testing. 11/24 patients were treated with IVIG. 8/24 patients required intubation and 4/24 died. 19/24 patients had decline in modified Rankin Scale (mRS) 90 days from discharge compared to baseline, with median mRS pre-WNND 1 (range 0-3) and post-WNND 3 (range 1-6).  

Descriptions of WNND in the setting of anti-CD20 treatment remain limited. This cohort emphasizes the importance of diagnostic CSF RT-PCR and need for targeted therapies given considerable morbidity and mortality.