Metagenomic sequencing test proves effective in diagnosing almost any kind of pathogen

Good news! A good diagnosis precedes a successful treatment!

"... It uses a powerful genomic sequencing technique, called metagenomic next-generation sequencing (mNGS).

Rather than looking for one type of pathogen at a time, mNGS analyzes all the nucleic acids, RNA and DNA, that are present in a sample. ...

The test has now been performed on thousands of patients with unexplained neurological symptoms, both at UCSF and other hospitals across the country.

In a paper ... the team demonstrated that the mNGS test correctly identified 86% of neurological infections. ...

In a companion study ... the team also used mNGS to identify pathogens in respiratory fluid that can cause pneumonia, and automated it to get results faster. ..."

From the abstract (1):

"Metagenomic next-generation sequencing (mNGS) of cerebrospinal fluid (CSF) is an agnostic method for broad-based diagnosis of central nervous system (CNS) infections. Here we analyzed the 7-year performance of clinical CSF mNGS testing of 4,828 samples from June 2016 to April 2023 performed by the University of California, San Francisco (UCSF) clinical microbiology laboratory. Overall, mNGS testing detected 797 organisms from 697 (14.4%) of 4,828 samples, consisting of 363 (45.5%) DNA viruses, 211 (26.4%) RNA viruses, 132 (16.6%) bacteria, 68 (8.5%) fungi and 23 (2.9%) parasites. We also extracted clinical and laboratory metadata from a subset of the samples (n = 1,164) from 1,053 UCSF patients. Among the 220 infectious diagnoses in this subset, 48 (21.8%) were identified by mNGS alone. The sensitivity, specificity and accuracy of mNGS testing for CNS infections were 63.1%, 99.6% and 92.9%, respectively. mNGS testing exhibited higher sensitivity (63.1%) than indirect serologic testing (28.8%) and direct detection testing from both CSF (45.9%) and non-CSF (15.0%) samples (P < 0.001 for all three comparisons). When only considering diagnoses made by CSF direct detection testing, the sensitivity of mNGS testing increased to 86%. These results justify the routine use of diagnostic mNGS testing for hospitalized patients with suspected CNS infection."

From the abstract (2):

"Tools for rapid identification of novel and/or emerging viruses are urgently needed for clinical diagnosis of unexplained infections and pandemic preparedness. Here we developed and clinically validated a largely automated metagenomic next-generation sequencing (mNGS) assay for agnostic detection of respiratory viral pathogens from upper respiratory swab and bronchoalveolar lavage samples in <24 h. The mNGS assay achieved mean limits of detection of 543 copies/mL, viral load quantification with 100% linearity, and 93.6% sensitivity, 93.8% specificity, and 93.7% accuracy compared to gold-standard clinical multiplex RT-PCR testing. Performance increased to 97.9% overall predictive agreement after discrepancy testing and clinical adjudication, which was superior to that of RT-PCR (95.0% agreement). To enable discovery of novel, sequence-divergent human viruses with pandemic potential, de novo assembly and translated nucleotide algorithms were incorporated into the automated SURPI+ computational pipeline used by the mNGS assay for pathogen detection. Using in silico analysis, we showed that after removal of all human viral sequences from the reference database, 70 (100%) of 70 representative human viral pathogens could still be identified based on homology to related animal or plant viruses. Our assay, which was granted breakthrough device designation from the US Food and Drug Administration (FDA) in August of 2023, demonstrates the feasibility of routine mNGS testing in clinical and public health laboratories, thus facilitating a robust and rapid response to the next viral pandemic."

Metagenomic sequencing test proves effective in diagnosing almost any kind of pathogen "A genomic test developed at UC San Francisco to rapidly detect almost any kind of pathogen—virus, bacteria, fungus or parasite—has proved successful after a decade of use."

1 Genomic Test Can Diagnose Nearly Any Infection (original news release) "Next-generation metagenomic sequencing test developed at UCSF proves its effectiveness in quickly diagnosing almost any kind of pathogen."

Seven-year performance of a clinical metagenomic next-generation sequencing test for diagnosis of central nervous system infections (open access)

Laboratory validation of a clinical metagenomic next-generation sequencing assay for respiratory virus detection and discovery (open access)

Fig. 1: Schematic of the mNGS assay workflow.