WNV-neutralizing plasma did not reduce death or functional decline in hospitalized older patients

BACKGROUND: In 2024, Israel faced a major West Nile virus (WNV) disease outbreak. We aimed to evaluate the efficacy and safety of WNV-neutralizing plasma for hospitalized patients with WNV disease. METHODS: We conducted a randomized, double-blind, placebo-controlled trial. Patients hospitalized with laboratory-confirmed symptomatic WNV disease, 60 years of age or older, or 18 to 59 years of age and immunocompromised, were eligible. Participants were randomly assigned (2:1) to donor-derived WNV-neutralizing plasma or placebo. The primary outcome was a composite of all-cause mortality and any functional deterioration at 30 days, defined as a decrease of more than 5 points from baseline on the Barthel Index (range 0-100; higher scores indicate greater independence) for activities of daily living (i.e., failure to return to pre-illness functional status). Key secondary outcomes included mortality, functional capacity (Barthel Index), and cognitive score (Modified Mini-Mental State Examination; range 0-30; higher scores indicate higher cognitive ability) at 30 and 90 days. RESULTS: Of the 34 participants enrolled, 22 were randomly assigned to the intervention group and 12 to placebo. Median age was 74 (interquartile range, 64-82), 50% were women, and 91% had neuroinvasive disease at enrollment. At 30 days, 11/22 (50%) and 6/12 (50%) patients in the treatment and placebo group, respectively, died or had functional deterioration (risk ratio [RR], 0.96; 95% confidence interval [CI], 0.51-1.79). Two patients (2/22) died in the intervention group, compared with 4 (4/12) in the placebo group (RR, 0.33, 95% CI, 0.09-1.15). The intervention was associated with higher functional capacity (Barthel Index 85 in the intervention group vs. 78 in the placebo group; RR, 1.15; 95% CI, 1.05-1.27), and higher cognitive scores (Mini-Mental score 25 vs. 22; RR, 1.24; 95% CI, 1.04-1.47) at 30 days. One (4.5%) allergic reaction was observed in the intervention group. CONCLUSIONS: In this small, randomized trial of predominantly severe neuroinvasive WNV, treatment with WNV-neutralizing plasma did not reduce the composite outcome of death or functional deterioration at 30 days compared to placebo. It was associated with improved cognitive and functional outcomes. Potential differences in mortality warrant further evaluation. (ClinicalTrials.gov number, NCT06590207.).