Nanopore metagenomic sequencing of influenza virus directly from respiratory samples: Diagnosis, drug resistance and nosocomial transmission, United Kingdom, 2018/19 influenza season

Yifei Xu*, Kuiama Lewandowski, Louise O. Downs, James Kavanagh, Thomas Hender, Sheila Lumley, Katie Jeffery, Dona Foster, Nicholas D. Sanderson, Ali Vaughan, Marcus Morgan, Richard Vipond, Miles Carroll, Timothy Peto, Derrick Crook, A. Sarah Walker, Philippa C. Matthews, Steven T. Pullan

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Influenza virus presents a considerable challenge to public health by causing seasonal epidemics and occasional pandemics. Nanopore metagenomic sequencing has the potential to be deployed for near-patient testing, providing rapid infection diagnosis, rationalising antimicrobial therapy, and supporting infection-control interventions. Aim: To evaluate the applicability of this sequencing approach as a routine laboratory test for influenza in clinical settings. Methods: We conducted Oxford Nanopore Technologies (Oxford, United Kingdom (UK)) metagenomic sequencing for 180 respiratory samples from a UK hospital during the 2018/19 influenza season, and compared results to routine molecular diagnostic standards (Xpert Xpress Flu/RSV assay; BioFire FilmArray Respiratory Panel 2 assay). We investigated drug resistance, genetic diversity, and nosocomial transmission using influenza sequence data. Results: Compared to standard testing, Nanopore metagenomic sequencing was 83% (75/90) sensitive and 93% (84/90) specific for detecting influenza A viruses. Of 59 samples with haemagglutinin subtype determined, 40 were H1 and 19 H3. We identified an influenza A(H3N2) genome encoding the oseltamivir resistance 533112 mutation in neuraminidase, potentially associated with an emerging distinct intra-subtype reassortant. Whole genome phylogeny refuted suspicions of a transmission cluster in a ward, but identified two other clusters that likely reflected nosocomial transmission, associated with a predominant community-circulating strain. We also detected other potentially pathogenic viruses and bacteria from the metagenome.

Conclusion: Nanopore metagenomic sequencing can detect the emergence of novel variants and drug resistance, providing timely insights into antimicrobial stewardship and vaccine design. Full genome generation can help investigate and manage nosocomial outbreaks.

Original languageEnglish
Article number2000004
Number of pages12
JournalEurosurveillance
Volume26
Issue number27
DOIs
Publication statusPublished - 8 Jul 2021

Bibliographical note

Funding Information:
PCM is funded by the Wellcome Trust (grant ref 110110) and holds an NIHR senior fellowship award. DWC, TEAP and ASW are NIHR Senior Investigators.

Funding Information:
Funding statement: The study was funded by the NIHR Oxford Biomedical Research Centre. Computation used the Oxford Biomedical Research Computing (BMRC) facility, a joint development between the Wellcome Centre for Human Genetics and the Big Data Institute supported by Health Data Research UK and the NIHR Oxford Biomedical Research Centre.

Publisher Copyright:
© 2021 European Centre for Disease Prevention and Control (ECDC). All rights reserved.

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