LUMC participates in super-fast European test to detect thousands of viruses at once
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To be better prepared for the next epidemic or pandemic, the European Union has allocated €24 million to the so-called RANGER* project. Clinical virologist Jutte de Vries (pictured right) is coordinator of LUMC work** within this project.
Super detective
The test works like a super detective that can detect different viruses in one sample, such as mucus, based on their unique genetic code. To do this, the European scientists in the RANGER project use a technique called metagenomic sequencing. This is a method for reading hereditary material (DNA or RNA) from a virus or other organism without knowing in advance which virus or organism you are looking for. According to De Vries, the latter is a major advantage over, say, a PCR test, which only allows you to detect a specific virus.
An example: Someone comes into the hospital with a fever and complaints of shortness of breath. In such a case, a doctor or nurse takes a swab through the nose or throat, which is then examined in the laboratory with a PCR test. This test recognizes only targeted genetic material from a predetermined virus, such as coronavirus. PCR is effective if you know in advance which virus or viruses you are looking for. But sometimes PCR offers no solution and the exact pathogen remains unknown. In such cases, a test based on metagenomic (literally: the whole of genomes, or “the complete DNA”) sequencing can offer a solution. “That makes the new test particularly valuable in detecting new or rare virus outbreaks,” says De Vries.
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More than viruses alone
Metagenomic sequencing is not limited to viruses, but can also detect other disease processors (pathogens) such as bacteria and fungi. This makes a superpathogen test possible, but even this is not yet on the market. Current regulations practically stand in the way of its introduction. "For each pathogen we have to provide a separate dossier, but how do you do that for thousands, sometimes still unknown pathogens? The way the rules are now, they don't fit this innovative, incredibly broad test. That makes the situation new for industry, academia and rule makers," says De Vries.
To still get approval, LUMC is working hard with the institutions involved and the European (EMA) and American (FDA) regulators to find a workable solution to this problem. A joint appeal in the scientific journal JAMA should help contribute to this.
Expertise
LUMC has long been doing metagenomic sequencing to detect viruses that are not found with a PCR test. "Take the astrovirus. It was known to cause diarrhea, but with this test it became clear that it can also cause damage in the brain. That link would never have been made with standard testing methods, because no one had yet associated the astrovirus with brain infections and it was therefore not tested for with PCR," says the clinical virologist.
But if LUMC already has this technique for finding viruses, why the RANGER project? De Vries: "As an academic hospital, LUMC is allowed to do such self-developed laboratory tests under strict conditions. Outside academic centers this is difficult because of the complex work process and the lack of bioinformatics expertise and facilities. In addition, sequencing is more expensive and takes longer to obtain a result compared to PCR. Commercial parties are also reluctant to step in because there is no guarantee that they will get approval to get their product on the market - after all, no one has done it before. This creates a stalemate. With RANGER, we hope to break it. In doing so, we are encouraged by the EU. Developing and getting this test approved to get the field moving is therefore an important deal we made with EU."
Better prepared for epidemics
The EU wants these types of tests to become more readily and widely available, as they contribute to better preparedness for epidemics. By acting together and with EU support, the partners involved hope to convince regulators to make the test available to a wide range of patients. The goal is to quickly detect infections whose cause is unknown - with a test result within six hours.
The project will take four years and proceed in three phases: developing the device, testing with patients in European hospitals - including LUMC - and obtaining European approval to market the test. De Vries explains: "In the first year we focus on design and practical feasibility, followed by user testing and an effectiveness study - how good is the test compared to current tests? - in the final year. In this way, we as LUMC fulfill a dual role: we advise as well as test the device - from early development to final clinical application."
* Also involved from the LUMC are: Medical Molecular Microbiologist Stefan Boers and bioinformatician Igor Sidorov.
** RANGER: RApid Next Generation Sequencing for Effective Medical Response.
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