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Clinical metagenomics for diagnosis and surveillance of viral pathogens

Nature Reviews Microbiology (2025)Cite this article

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Abstract

Metagenomics is becoming more widely used for diagnosis of viral infections and surveillance of viruses. Its pathogen-agnostic approach makes metagenomics useful for unknown and novel infection diagnosis, outbreak investigation, and new and emerging pathogen surveillance. New metagenomics methods, such as the use of rapid sequencing technologies and approaches that can selectively enrich for a wide range of viruses, are expanding the range of clinical and public health scenarios in which metagenomics can be used. Following the COVID-19 pandemic, there is increasing interest in viral surveillance worldwide, using clinical samples, potential zoonotic reservoirs and environmental sources, such as wastewater. Validation and accreditation of metagenomics protocols to ensure quality, together with further innovation in methods, will be necessary to bring metagenomics into routine service in clinical and public health laboratories.

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Fig. 1: Clinical metagenomics workflow.
Fig. 2: Summary of bioinformatics analysis for metagenomics for viral detection.

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Acknowledgements

The authors acknowledge the clinical metagenomics team at Great Ormond Street Hospital and colleagues at University College London Genomics. O.E.T.M., S.B. and S.M. acknowledge the support of the National Institute for Health Research Blood and Transplant Research Unit in Genomics to Enhance Microbiology Screening (NIHR BTRU-GEMS). All research at Great Ormond Street Hospital NHS Foundation Trust and UCL Great Ormond Street Institute of Child Health is made possible by the NIHR Great Ormond Street Hospital Biomedical Research Centre. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health.

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  1. These authors contributed equally: Oscar Enrique Torres Montaguth, Sarah Buddle.

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  1. Infection, Immunity and Inflammation Department, Great Ormond Street Institute of Child Health, University College London, London, UK

    Oscar Enrique Torres Montaguth, Sarah Buddle, Sofia Morfopoulou & Judith Breuer

  2. Department of Microbiology, Virology and Infection Prevention & Control, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK

    Judith Breuer

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Competing interests

J.B. receives research support from Illumina PLC, Oxford Nanopore Technologies, and Twist Bioscience. O.E.T.M., S.B. and J.B. are authors on a patent application concerning the use of target capture sequencing with ONT. S.M. declares no competing interests.

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Related links

ISO/IEC 17025:2017: https://www.virology.uzh.ch/de/services.html

NCBI RefSeq: https://www.ncbi.nlm.nih.gov/refseq/

Six sequences of the novel coronavirus: https://virological.org/t/novel-2019-coronavirus-genome/319

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Torres Montaguth, O.E., Buddle, S., Morfopoulou, S. et al. Clinical metagenomics for diagnosis and surveillance of viral pathogens. Nat Rev Microbiol (2025). https://doi.org/10.1038/s41579-025-01223-5

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