mNGS detects Sindbis virus in cerebrospinal fluid, revealing neuroinvasive potential in human infections
Investigators report the first detection of Sindbis virus RNA in the cerebrospinal fluid of four patients with acute neurological symptoms in Italy, using metagenomic next generation sequencing. Complete viral genomes were reconstructed and phylogenetic analysis identified co-circulating Clade D lineages, establishing a direct link between the mosquito-borne alphavirus and central nervous system involvement. The findings expand the recognized clinical spectrum of Sindbis virus beyond arthritogenic disease and demonstrate the utility of mNGS for identifying atypical neurotropic pathogens. Laboratories in endemic regions should consider Sindbis virus in the differential diagnosis of viral CNS infections and prioritize enhanced molecular surveillance.
The original study
Molecular evidence of neuroinvasive Sindbis virus infection in humans: detection in cerebrospinal fluid by next generation sequencing.
- Authors
- Cusi MG, Savellini GG, Cassol C, Nencioni C, Bernini L, Tacconi D, et al.
- Journal
- Emerging microbes & infections
- Type
- Journal Article
- PMID
- 42434987
Original abstract
Sindbis virus (SINV) is a mosquito borne alphavirus causing seasonal outbreaks in northern Europe, Africa and Russia. Neurological involvement in humans is poorly documented, and detection in cerebrospinal fluid (CSF) has not previously been reported. This study provides the first unequivocal evidence of human CNS involvement by detecting SINV RNA directly in the cerebrospinal fluid of four autochthonous patients presenting with acute neurological symptoms in south eastern Tuscany, Italy, July-August 2025. Utilizing metagenomic Next Generation Sequencing (mNGS), we reconstructed complete viral genomes, strongly supporting a causal relationship between SINV and neurological manifestations. Phylogenetic analysis revealed a complex epidemiological landscape in Italy characterized by the co-circulation of Clade D lineages. Our findings fundamentally expand the clinical spectrum of SINV, demonstrating that it is not merely an arthritogenic pathogen, but a neuroinvasive threat to humans. This highlights the critical need to include SINV in the differential diagnosis of viral CNS infections in endemic areas and underscores the urgency for enhanced European laboratory surveillance.