Metagenomic analysis by massive parallel sequencing is a high‑complexity molecular technique that sequences all genetic material in a sample to identify viruses, bacteria, fungi, and parasites without knowing the target in advance. Its diagnostic application, clinical metagenomics (mNGS), is emerging as a transformative approach in infectious disease diagnostics, and mNGS tests are rapidly entering routine clinical practice. Three ESCV‑ENNGS members, together with Charles Chiu (UCSF), have led a systematic Review in The Lancet Infectious Diseases that evaluates the real clinical impact of mNGS for severe infections and how it can improve care pathways and therapeutic decisions.
Focusing on more than 100 prospective clinical studies, the Review provides a real‑world picture of how mNGS is being used to diagnose infections in hospitalised patients. The strongest data come from intensive care settings, where mNGS improves the diagnosis of severe or atypical pneumonias in mechanically ventilated patients and supports faster, more targeted antimicrobial management. mNGS is also clinically useful in complex cases of meningitis or encephalitis in which conventional testing fails to identify a pathogen, and in high‑risk groups such as oncology and transplant patients or those with profound immunosuppression, where rapid pathogen detection can be critical for survival.
Across syndromes, the most frequent use of clinical mNGS is in difficult‑to‑diagnose infections and in the detection of drug‑resistant or unexpected pathogens. This enables clinicians to adjust, escalate, de‑escalate or even discontinue empirical antibiotics more confidently and, in selected settings, can shorten time to appropriate therapy. Overall, the current body of evidence supports the performance of clinical mNGS, its clear utility in multiple specific “difficult‑to‑diagnose” scenarios, and its potential as a truly transformative diagnostic test for infectious diseases.
- Xavier López‑Labrador, based at the University of Valencia and serving as speaker for ESCV‑ENNGS, underlines that “Clinical metagenomics is moving from proof‑of‑concept into carefully defined, real‑world indications, where it complements rather than replaces conventional microbiology and helps us treat the sickest patients more precisely.”
Original Article:
Julianne R. Brown, Charles Y. Chiu, F. Xavier López-Labrador, Jutte J. C. de Vries, The impact of clinical metagenomic testing on patient management: facts versus fantasy, The Lancet Infectious Diseases, 2026, ISSN 1473-3099, https://doi.org/10.1016/S1473-3099(26)00106-4.