Viral capture sequencing detects unexpected viruses in the cerebrospinal fluid of adults with meningitis - 08/04/22

Doi : 10.1016/j.jinf.2021.12.042

Fiona McGill ^a,^d,^k,^l,^⁎ , Rafal Tokarz ^b, Emma C Thomson ^c, Ana Filipe ^c, Stephen Sameroff ^b, Komal Jain ^b, Nishit Bhuva ^b, Shirin Ashraf ^c, W. Ian Lipkin ^b, Caroline Corless ⁿ, Chitra Pattabiraman ^a,^m, Barry Gibney ^e, Michael J Griffiths ^a,^f,^l, Anna Maria Geretti ^a,^d,^o, Benedict D Michael ^a,^g,^l, Nicholas J Beeching ^d,^h,^l, David McKee ⁱ, Ian J Hart ⁿ, Ken Mutton ^j, Agam Jung ^k, Alastair Miller ^a, Tom Solomon ^a,^g,^l,^⁎
^a Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, UK
^b Center for Infection and Immunity, Mailman School of Public Health, Columbia University, NY, USA
^c Institute of infection, immunity and inflammation, University of Glasgow, Glasgow, UK
^d Tropical and Infectious Disease Unit, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK
^e UK Health Security Agency (previously Public Health England), UK
^f Alder Hey Children's NHS Foundation Trust, Liverpool, UK
^g Department of Neurology, The Walton Centre NHS Foundation Trust, Liverpool, UK
^h Liverpool School of Tropical Medicine, Liverpool, UK
ⁱ Central Manchester Foundation Trust, Manchester, UK
^j University of Manchester, Manchester, UK
^k Leeds Teaching Hospitals NHS Trust, Leeds, UK
^l National Institute for Health Research Health Protection Research Unit in Emerging and Zoonotic Infections, University of Liverpool, Liverpool, UK
^m National Institute for Mental Health and Neurosciences, Bangalore, India
ⁿ Liverpool Specialist virology centre, Department of Infection and Immunity, Liverpool Clinical Laboratories, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK
^o Faculty of Medicine, University of Rome Tor Vergata

^⁎Corresponding authors at: National Institute for Health Research Health Protection Research Unit on Emerging and Zoonotic Infections, University of Liverpool, Liverpool, UK.National Institute for Health Research Health Protection Research Unit on Emerging and Zoonotic InfectionsUniversity of LiverpoolLiverpoolUK

Highlights

•	Viral capture sequencing detected a virus in 42% of patients with meningitis.
•	Potentially pathogenic virus detected in 68% of those.
•	Capture sequencing allows detection of unexpected pathogens.

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Abstract

Objectives

Many patients with meningitis have no aetiology identified leading to unnecessary antimicrobials and prolonged hospitalisation. We used viral capture sequencing to identify possible pathogenic viruses in adults with community-acquired meningitis.

Methods

Cerebrospinal fluid (CSF) from 73 patients was tested by VirCapSeq-VERT, a probe set designed to capture viral targets using high throughput sequencing. Patients were categorised as suspected viral meningitis – CSF pleocytosis, no pathogen identified (n = 38), proven viral meningitis – CSF pleocytosis with a pathogen identified (n = 15) or not meningitis – no CSF pleocytosis (n = 20).

Results

VirCapSeq-VERT detected virus in the CSF of 16/38 (42%) of those with suspected viral meningitis, including twelve individual viruses. A potentially clinically relevant virus was detected in 9/16 (56%). Unexpectedly Toscana virus, rotavirus and Saffold virus were detected and assessed to be potential causative agents.

Conclusion

VirCapSeq-VERT increases the probability of detecting a virus. Using this agnostic approach we identified Toscana virus and, for the first time in adults, rotavirus and Saffold virus, as potential causative agents in adult meningitis. Further work is needed to determine the prevalence of atypical viral candidates as well as the clinical impact of using sequencing methods in real time. This knowledge can help to reduce antimicrobial use and hospitalisations leading to both patient and health system benefits.

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Keywords : Meningitis, Viral, High throughput sequencing, Toscana virus, Rotavirus, Saffold virus

Plan

Detection of commonly recognised pathogens

Detection of potential viral bystanders

Detection of unexpected viruses

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Vol 84 - N° 4

P. 499-510 - avril 2022 Retour au numéro

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Viral capture sequencing detects unexpected viruses in the cerebrospinal fluid of adults with meningitis - 08/04/22

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