# West Nile Virus Lineage 2 Neuroinvasive Infection Presenting as Intraparenchimal Cerebral Hemorrage

## TL;DR

This study reports on nine adult cases of neuroinvasive West Nile virus infection in Italy, highlighting cerebral hemorrhage and other severe neurological complications.

## Contribution

The paper presents new clinical and phylogenetic data on West Nile virus lineage 2 in Southern Italy, including rare manifestations like cerebral hemorrhage.

## Key findings

- Nine WNDD cases showed severe neurological symptoms, including cerebral hemorrhage and Guillain–Barré syndrome.
- Phylogenetic analysis grouped Italian WNV strains with Central–Southern–Eastern European sequences, distinct from northern Italian strains.
- The study identified sub-lineage 2a of WNV-2, clustering mainly with Hungarian sequences.

## Abstract

Objective: The aim of this retrospective study was to evaluate clinical and laboratory characteristics in adult patients with neuroinvasive West Nile virus (WNDD). We also studied the phylogeny and molecular characteristics of some of the WNV strains. Methods: A retrospective analysis was conducted at “Annunziata” Hub Hospital, a secondary referral facility in Calabria region, in Southern Italy. Sample pre-processing, sequencing and bioinformatic analyses were carried out at IRCCS Sacro Cuore Don Calabria Hospital in Negrar di Valpolicella, Verona, Veneto region in North-East Italy. Results: Nine cases of WNDD were analyzed, involving eight males and one female, with a mean age of 70.33 years (range 60–85). The overall average hospital stay was 20.6 days (range 6–46). Six patients made a full recovery after a mean of 35.3 days of acute care. Thirty-day mortality rate was 23%. VNDD in some of our patients manifested itself in the form of cerebral hemorrhage (ICH) in three patients, causing lethality in two patients and other unusual manifestations, such as Guillain–Barré syndrome with fatal outcome and severe facial palsy. Phylogenetic analysis shows that our sequences are closely related to other southern-Italian and cluster with Central–Southern–Eastern European sequences, while being evidently separated from northern Italian and Central–Western European ones, belonging to the sub-lineage 2a of the WNV-2, clustering with sequences from the Central–South–Eastern clade, mainly to Hungary. Conclusions: Cerebrovascular complications of WNE may be an important clinical manifestation of WNV neuroinvasive infection. Preliminary data do not allow us to determine whether our strains, closely related to other southern-Italian and cluster with Central–Southern–Eastern European sequences, really presented an increased neurovirulence.