Inflammatory Response Associated with West Nile Neuroinvasive Disease: A Systematic Review.

BACKGROUND: West Nile virus (WNV) infection is a seasonal arbovirosis with the potential to cause severe neurological disease. Outcomes of the infection from WNV depend on viral factors (e.g., lineage) and host-intrinsic factors (e.g., age, sex, immunocompromising conditions). Immunity is essential to control the infection but may also prove detrimental to the host. Indeed, the persistence of high levels of pro-inflammatory cytokines and chemokines is associated with the development of blood-brain barrier (BBB) damage. Due to the importance of the inflammatory processes in the development of West Nile neuroinvasive disease (WNND), we reviewed the available literature on the subject. METHODS: According to the 2020 updated PRISMA guidelines, all peer-reviewed articles regarding the inflammatory response associated with WNND were included. RESULTS: One hundred and thirty-six articles were included in the data analysis and sorted into three groups (in vitro on-cell cultures, in vivo in animals, and in humans). The main cytokines found to be increased during WNND were IL-6 and TNF-α. We highlighted the generally small quantity and heterogeneity of information about the inflammatory patterns associated with WNND. CONCLUSIONS: Further studies are needed to understand the pathogenesis of WNND and to investigate the extent and the way the host inflammatory response either helps in controlling the infection or in worsening the outcomes. This might prove useful both for the development of target therapies and for the development of molecular markers allowing early identification of patients displaying an inflammatory response that puts them at a higher risk of developing neuroinvasive disease and who might thus benefit from early antiviral therapies.

The WEST Study: A Retrospective and Multicentric Study on the Impact of Steroid Therapy in West Nile Encephalitis.

Background: The use of steroid therapy in potentially life-threatening neuroinvasive forms of West Nile infection (WNND) is controversial. The aim of this study is to assess the efficacy of steroid therapy in reducing intrahospital mortality, length of stay, and neurological sequelae at discharge. Methods: This was a multicenter, retrospective, observational study conducted in 5 hospitals in Northern Italy, headed by the Fondazione IRCSS Policlinico San Matteo (Pavia). We extracted all patient data with WNND diagnoses, comparing patients who received steroid treatment with patients who did not receive steroid treatment between January 2014 and January 2022. Comparisons between the 2 groups were performed using chi-square tests for categorical variables and Mann-Whitney tests for non-normal continuous data, and a generalized linear model for the binomial family was carried out. Results: Data from 65 WNND patients were extracted. Among these patients, 33 (50.7%) received steroid therapy at any point during their hospitalization. Receiving steroid therapy did not significantly reduce intrahospital mortality (odds ratio [OR], 1.70; 95% CI, 0.3-13.8; P = .89) or neurological sequelae at discharge (OR, 0.53; 95% CI, 0.16-1.76; P = .47). Conclusions: Steroid treatment is currently used on a single-case basis in severe WNND. More prospective data are needed to demonstrate a protective effect on mortality and neurological sequelae.