Reporting and interpretation of respiratory metagenomic results in clinical practice: a systematic review and consensus guidelines from the UK NHS Respiratory Metagenomics Network

Abstract Background: Metagenomic next-generation sequencing (mNGS) offers culture-independent pathogen detection and is increasingly being adopted in clinical practice. However, approaches to reporting and interpreting metagenomic results remain poorly standardised. No previous society or professional guidelines exist for reporting and interpretation of metagenomic data. We aimed to synthesise current practice and evidence, identify gaps in knowledge, and to develop national consensus statement for clinical reporting and interpretation of respiratory metagenomics. Methods: We undertook a systematic review of studies using metagenomic sequencing for clinical reporting and interpretation of human respiratory samples following PRISMA guidelines. The findings were informed by two workshops and a three-round Delphi process involving clinicians (physicians, microbiologists, virologists and clinical scientists) within the UK National Health System (NHS) Respiratory Metagenomics Network. Results: For the systematic review, 53 studies including 6,000 participants met inclusion criteria but showed high heterogeneity in reporting and interpretation practices with a high risk of bias. Nineteen panellists from six NHS sites participated in the workshops and Delphi process with 27 statements reaching consensus. The guidelines provide principles for setting detection thresholds, using negative controls, reporting of detections, and interpretation of findings. A decision algorithm for reporting respiratory metagenomic results is presented. Knowledge gaps and priorities for future research were identified. Conclusions: Use of respiratory metagenomic tests in practice is heterogeneous and often at risk of bias or subjective interpretation. Our consensus statement supports transparent, standardised interpretation and reporting of respiratory metagenomic results, and highlights priorities for future research and validation studies.