Feasibility and clinical utility of local rapid Nanopore influenza A virus whole genome sequencing for integrated outbreak management, genotypic resistance detection and timely surveillance

Tom G.S. Williams*, Luke B. Snell, Christopher Alder, Themoula Charalampous, Adela Alcolea-Medina, Jasveen K. Sehmi, Noor Al-Yaakoubi, Gul Humayun, Shahjahan Miah, Angie Lackenby, Maria Zambon, Rahul Batra, Sam Douthwaite, Jonathan D. Edgeworth, Gaia Nebbia*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

Rapid respiratory viral whole genome sequencing (WGS) in a clinical setting can inform real-time outbreak and patient treatment decisions, but the feasibility and clinical utility of influenza A virus (IAV) WGS using Nanopore technology has not been demonstrated. A 24 h turnaround Nanopore IAV WGS protocol was performed on 128 reverse transcriptase PCR IAV-positive nasopharyngeal samples taken over seven weeks of the 2022–2023 winter influenza season, including 25 from patients with nosocomial IAV infections and 102 from patients attending the Emergency Department. WGS results were reviewed collectively alongside clinical details for interpretation and reported to clinical teams. All eight segments of the IAV genome were recov-ered for 97/128 samples (75.8%) and the haemagglutinin gene for 117/128 samples (91.4%). Infection prevention and control identified nosocomial IAV infections in 19 patients across five wards. IAV WGS revealed two separate clusters on one ward and excluded transmission across different wards with contemporaneous outbreaks. IAV WGS also identified neuraminidase inhibi-tor resistance in a persistently infected patient and excluded avian influenza in a sample taken from an immunosuppressed patient with a history of travel to Singapore which had failed PCR subtyping. Accurate IAV genomes can be generated in 24 h using a Nanopore protocol accessible to any laboratory with SARS-CoV-2 Nanopore sequencing capacity. In addition to replicat-ing reference laboratory surveillance results, IAV WGS can identify antiviral resistance and exclude avian influenza. IAV WGS also informs management of nosocomial outbreaks, though molecular and clinical epidemiology were concordant in this study, limiting the impact on decision-making.

Original languageEnglish
Article number001083
JournalMicrobial Genomics
Volume9
Issue number8
DOIs
Publication statusPublished - 1 Aug 2023

Bibliographical note

Publisher Copyright:
© 2023 The Authors.

Keywords

  • Nanopore
  • antiviral drug resistance
  • avian influenza
  • influenza A
  • nosocomial outbreaks
  • whole genome sequencing

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