Viral metagenomic sequencing reveals rare pathogens and improves diagnostic accuracy in neuroinflammatory disorders

Neuroinflammatory disorders are frequently of unknown aetiology. Unbiased metagenomic next-generation sequencing of cerebrospinal fluid could help bridge the current diagnostic gap by identifying more infectious pathogens inducing central nervous system disorders. This study examined the advantages of adding viral metagenomics to standard testing procedures.

Patients presenting with symptoms indicative of a neuroinflammatory disorder were enrolled at a Swiss tertiary care hospital through prospective and retrospective recruitment. Participants were diagnosed with infectious or autoimmune neuroinflammatory disorders based on the results of routine diagnostics and viral metagenomic sequencing.

Of the 70 study participants, 50 were classified as having an infectious disorder. Among these, a total of 37 pathogens were identified in 29 individuals (56 %), including 32 viral, three bacterial, one fungal, and one prion infection. Conventional virus testing and viral metagenomic sequencing produced the same positive and negative results for 13 and 21 cases, respectively. This resulted in an overall percent agreement of 59 %. Disparate viral results were observed in 19 cases. Ten cases were detected only by conventional testing, and nine were detected only by viral metagenomics. Notably, we report the detection of Toscana virus by viral metagenomic sequencing, a relatively rare pathogen in Switzerland that is not routinely screened for, underscoring the advantages of integrating viral metagenomics with conventional testing.

Viral metagenomic sequencing as a first-line diagnostic tool in combination with conventional methods yields the most comprehensive results to diagnose patients with infectious neuroinflammatory disorders. Its unbiased approach enables the detection of rare or unconsidered viruses.