Clinical spectrum, outcomes, and risk factors of West Nile virus infection: a systematic review and meta-analysis

Abstract

Background West Nile virus (WNV) infection has a broad and heterogeneous clinical spectrum, yet systematic syntheses focusing on clinically and laboratory-confirmed cases remain limited. Objectives To characterize the clinical spectrum reported in clinically recognized, laboratory-supported WNV cases, explore differences in symptom profiles according to plaque reduction neutralization test (PRNT) confirmation status, and summarize environmental risk factors described in the clinical literature. Method This study was registered in PROSPERO (CRD420250650535) and conducted according to PRISMA guidelines. Results A total of 4062 patients with West Nile virus (WNV) infection from 39 published studies were analysed. Most patients were male (55%), with a mean age of 52. The pooled mortality proportion was 6.23%, increasing to 62% among intensive care unit patients. Central nervous system manifestations were the most frequent (39.39%), followed by systemic (31.21%) symptoms. Only 53% of reported cases were confirmed by PRNT, while the remaining cases were diagnosed using other laboratory-based methods. Cases without PRNT confirmation more often presented with nonspecific symptoms, whereas PRNT-confirmed cases showed a more consistent neurological profile. Conclusion West Nile virus infection is a multisystemic disease associated with substantial morbidity and mortality, particularly in neuroinvasive cases. Improved recognition of symptom patterns may facilitate earlier diagnosis. Expanding access to confirmatory diagnostic and strengthening surveillance, especially in at-risk regions, is essential to reduce misclassification bias among clinically recognised WNV cases and improve public health preparedness.