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.
According to the 2020 updated PRISMA guidelines, all peer-reviewed articles regarding the inflammatory response associated with WNND were included.
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.
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.

In October 2020, the first case of autochthonous West Nile virus neuroinvasive disease was diagnosed in the Netherlands with a presumed infection in the last week of August. Investigations revealed five more cases of local West Nile virus (WNV) infection. The cases resided in a region where WNV was detected in a bird and mosquitoes in August 2020. Molecular analysis was successful for two cases and identified the presence of WNV lineage 2.

West Nile virus (WNV) is one of the most prevalent mosquito-borne viruses. Although the infection in humans is mostly asymptomatic, 15-20% of cases show flu-like symptoms with fever. In 1% of infections, humans develop severe nervous symptoms and even die, a condition known as West Nile neuroinvasive disease (WNND). The aim of our study was to analyze the influence of abiotic and biotic factors with the human WNND cases during the period 2015-2019. A database containing all the localities in Romania was developed. Abiotic and biotic predictors were included for each locality: geographic variables, climatic data, and biotic factors. Spatial distribution of the WNND infections was analyzed using directional distribution (DD). The Spearman\'s rank correlation coefficient was employed to assess the strength of association between the WNND infections and predictors. A model was generated using the random forest ensemble learning method. A total number of 535 human WNND cases were confirmed in 308 localities. The DD showed a south-eastern geographical distribution. Weak correlation was observed between the number of human WNND cases for each year and the predictors. The highest predicted probability was around urbanized patches in the south and southeast. Increased surveillance and control measures of vectors in risk areas should be implemented and educational campaigns should be made available for the general public in order to raise awareness of the disease and inform the population about prophylactic measures.

West Nile virus (WNV) is a flavivirus transmitted by mosquitoes. Birds are the reservoir for the virus; humans, horses and other mammals are dead-end hosts. Infections caused by WNV in humans can vary from asymptomatic infections to West Nile fever (WNF) or West Nile neuroinvasive disease (WNND). In 1995, a serosurvey was performed in Slovenia on forest workers, and WNV specific IgG antibodies were confirmed in 6.8% of the screened samples, indicating that WNV is circulating in Slovenia. No human disease cases were detected in Slovenia until 2013, when the first case of WNV infection was confirmed in a retrospective study in a 79-year old man with meningitis. In 2018, three patients with WNND were confirmed by laboratory tests, with detection of IgM antibodies in the cerebrospinal fluid of the patients. In one of the patients, WNV RNA was detected in the urine sample. In 2017, 2018 and 2019, a mosquito study was performed in Slovenia. Mosquitoes were sampled on 14 control locations and 35 additional locations in 2019. No WNV was detected in mosquitoes in 2017 and 2019, but we confirmed the virus in a pool of Culex sp. mosquitoes in 2018. The virus was successfully isolated, and complete genome sequence was acquired. The whole genome of the WNV was also sequenced from the patient\'s urine sample. The whole genome sequences of the WNV virus detected in Slovenian patient and mosquito indicate the virus most likely spread from the north, because of the geographic proximity and because the sequences cluster with the Austrian and Hungarian sequences. A sentinel study was performed on dog sera samples, and we were able to confirm IgG antibodies in 1.8% and 4.3% of the samples in 2017 and 2018, respectively. Though Slovenia is not a highly endemic country for WNV, we have established that the virus circulates in Slovenia.

Infection with West Nile virus (WNV) has a well-characterized acute disease process. However, long-term consequences are less understood. We searched death records for 4,142 residents of Texas, USA, infected with WNV during 2002-2012 and identified 557 (13%) deaths. We analyzed all-cause and cause-specific deaths after WNV infection by calculating standardized mortality ratios and using statewide mortality data. Acute-phase deaths (<90 days after symptom onset) occurred in 289 (7%) of case-patients; of those deaths, 289 (92%) were cases of West Nile neuroinvasive disease (WNND). Convalescent-phase deaths (>90 days after symptom onset) occurred in 268 (7%) of the remaining 3,853 case-patients; 210 (78%) of these deaths occurred in patients with WNND. Convalescent-phase WNND case-patients showed excess deaths from infectious and renal causes; case-patients <60 years of age had increased risk for all-cause death, specifically from renal, infectious, digestive, and circulatory causes. We provide population-level evidence of increased risk for death after WNV infection resulting in WNND.