The Pathologist: Sequencing-Based Metagenomics Could Improve Respiratory Testing
It’s no wonder physicians take respiratory infections so seriously. They’re a leading cause of sepsis, a significant driver of antibiotic utilisation, and a potential trigger for new pandemics.
In a commentary article published in The Pathologist, infectious disease expert Jonathan Edgeworth wrote about the need for a new approach to diagnosing and treating respiratory infections, based on metagenomic sequencing. With his roles as professor of clinical infectious diseases at King’s College London and consultant microbiologist at Guy’s and St. Thomas’ NHS Foundation Trust, Jonathan has the expertise to support this valuable perspective. (We’re also very fortunate that he serves as VP, Medical Affairs here at Oxford Nanopore Technologies).
The commentary is short, but we’ve included highlights here if you don’t have a chance to check it out.
Status quo
Currently, the most common test used for respiratory infections is the same one used a century ago: culture. It takes days for a culture-based test to identify the pathogen responsible for an infection — and some pathogens can’t even be grown in culture, or grow so slowly it’s not relevant for clinical use. Another challenge is detecting markers of antibiotic resistance, which are essential for getting patients on the right treatment.
‘In healthcare systems where respiratory infection testing is based solely on cultures, there is no opportunity to adjust a patient’s treatment’, Jonathan wrote. ‘Not only does it lead to poorer patient outcomes, but it also contributes to the growing epidemic of antibiotic resistance’.
Molecular diagnostic platforms can be used as an alternative or as a supplement to culture-based testing, but they have their own challenges. Tests are only able to identify pathogens that clinicians know to look for, so ‘rare, novel, or emerging pathogens are missed by these tests’, Jonathan noted.
The metagenomic approach
Clinicians have the opportunity for faster and more reliable tests through a concept commonly used in the research world: metagenomic sequencing. This technique uses modern sequencing tools to analyse all organisms in a small biological community. In a respiratory test, sequencing-based metagenomics could make it possible to identify every virus, bacterium, and fungus present in a clinical sample.
Metagenomics has been limited by short-read sequencing, which produces such tiny snippets of DNA that it is not always possible to identify a pathogen or connect drug-resistance markers to their host. ‘Long-read sequencing platforms can help address the alignment challenges associated with short-read data; they can also fully resolve more complex genomes, such as those characteristic of fungal pathogens’, Jonathan explained. ‘With long-read data, it is also possible to link resistance-carrying plasmids to their host genomes’.
Metagenomics in action
The commentary points to an example from Guy’s and St. Thomas’ Hospital NHS Foundation Trust in London, where clinical lab members deployed nanopore sequencing for a rapid metagenomics-based workflow for respiratory testing. In most cases, the team delivered same-day results to clinicians.
‘Interestingly, nearly half of the results led to shifts in antimicrobial selection’, Jonathan reported. ‘Several unexpected organisms and cases of co-infections were reported; these would not have been found with conventional tests’.
Noting that additional evaluations will be needed before the value of sequencing-based metagenomics can be fully understood for respiratory testing, Jonathan concluded that ‘rapid metagenomics has the potential to serve as a one-and-done test for respiratory infections to ease the testing burden on clinical laboratories and help physicians deliver better outcomes for their patients’.