NEW YORK – A European research consortium will pilot three new point-of-care platforms for diagnosing SARS-CoV-2, the virus that causes COVID-19, in patients. Called CoronaDx, the effort has a budget of €3 million ($3.5 million) and will run through April 2023.
Investigators at the Technical University of Denmark (DTU) are leading CoronaDx, which commenced earlier this year. Other participants include Statens Serum Institut (SSI), a Danish research institute; the Medical University of Vienna; Gothenburg, Sweden-based TATAA Biocenter; and the Università Vita-Salute San Raffaele and Fondazione iCons in Italy.
CoronaDx also involves two Chinese partners, Sun Yat-sen University and the Chinese Center for Disease Control and Prevention, which will test the new platforms in the field. The EU is funding CoronaDx via its Horizon 2020 program.
The aim of CoronaDx is to develop three point-of-care systems for clinical application, including one front-line platform and two second-line diagnostic platforms. The intent is that these systems will find use in remote areas that have limited infrastructure, according to investigators.
Pathag is the front-line test under evaluation. It relies on antibodies to the virus that are fixed to microscopic latex beads. The latex fixation assay can be carried out on paper strips using nasopharyngeal swab or sputum samples and read visually, making it an inexpensive POC test. Developers foresee its use as a screening tool in airports and quarantine settings.
The other two tests in development are Pathpod, which relies on a loop-mediated isothermal amplification (LAMP) assay run on a portable instrument to diagnose SARS-CoV-2 infection within 30 minutes; and Pathlock, which uses CRISPR-Cas13 to recognize SARS-CoV-2, and register signals when the virus has been cut. Clinicians can register the signal using lateral flow assays, according to developers. They are positioning the test for use in field labs and mobile clinics.
Much of the initial work on the three platforms was underway prior to the outbreak of the COVID-19 pandemic last year. Lead investigator Anders Wolff, a professor of biotechnology and biomedicine at DTU, said that the LAMP-based Pathpod platform emerged from a separate EU project called Vivaldi that focused on applying the technology for the detection of different animal viruses. The Vivaldi system is capable of processing 10 samples per run on disposable cartridges and is as accurate as real-time PCR, though developers claim that it is faster.
"We were making a system based on LAMP for detecting different pathogens in animals," noted Wolff. "In the middle of evaluating the system, the coronavirus pandemic broke loose," he said. "We thought maybe we could use the system for detecting the coronavirus and that was the beginning of the CoronaDx project."
Numerous companies have also turned to LAMP as an alternative to RT-PCR, which has emerged as the standard technique for diagnosing SARS-CoV-2. Wolff maintained that the technique is preferable to PCR because it's faster and simpler. "We just take a swab sample, heat treat it for five minutes, and then use that in the assay," he said. "It's done without any purification step and that is of course cheaper and faster because you don't have to do that step."
Of the three platforms, Pathpod has the most imminent commercial future. Wolff said the DTU investigators are working with TATAA in Sweden to commercialize the Pathpod platform through collaboration with a large pharmaceutical partner. He said that they are currently looking for such a partner to make the platform available for sale. The test instrument weighs about 1.2 kg and supports analysis of 10 samples plus a positive and negative control. All reagents are already included in the consumable cartridges, he noted. "You just have to put the sample in the cartridge, put it in the machine and press start," said Wolff. "It's well suited for point of care."
Pathag and Pathlock
Pathag and Pathlock, the other two platforms being assessed via CoronaDx, were developed within SSI, which functions as a national center for disease control in Denmark and is based in the capital Copenhagen. Wolff said that rather than looking to commercialize these tests, SSI will instead share them among other reference laboratories in Europe, as soon as early next year.
Indeed, Hans-Christian Slotved, a senior scientist at SSI, said that Pathag, the latex fixation assay that can be carried out on strips of paper, could be ready by January. Like Wolff, Slotved had been developing Pathag for a different application, in his case, testing for diverse bacteria and viruses, when COVID-19 struck. The assay has thus also been repurposed for detecting the virus.
"We needed some speedy tests," acknowledged Slotved. At the beginning of the pandemic, European officials scrambled to adopt a variety of rapid tests for mass SARS-CoV-2 testing, in some cases returning batches of assays to manufacturers because of subpar test performance.
Pathag is a potential solution to this need, given its inexpensive footprint and potential high accuracy. Slotved said that it was natural that the community has faced issues early on, as COVID-19 is a new disease, and it takes time to prepare reliable point-of-care tests for use.
"It's the time factor of going back to scratch and then developing everything," said Slotved. "For a lot of diseases that have been around for years, you already have the sera and what you need to develop tests, but for COVID-19, which is quite new, you have to build it from scratch," he said.
So far, Slotved said, the SSI researchers have established proof of concept for Pathag and that the "sensitivity and specificity of the test is excellent." He also said that SSI has access to plenty of standard swab samples to validate the assay. "We have the capacity to test it, build it up, and test it on samples," he said. "We hope to have it ready by 2021, the new year, that is our goal."
Like Pathag, CRISP-Cas13 Pathlock does not have a commercial future, but instead will be shared among kindred reference labs. The investigators responsible for Pathlock did not respond to a query seeking comment. Several other groups have sought to apply CRISPR-Cas13 to diagnose SARS-CoV-2. A Chinese team published a study in August that described a new approach that combines isothermal amplification and CRISPR-Cas13a to detect the virus. In the paper, the researchers also compared their method to metagenomic next-generation sequencing and reverse-transcription PCR-based tests.
In May, Sherlock Biosciences received Emergency Use Authorization from the US Food and Drug Administration for its Sherlock CRISPR SARS-CoV-2 kit. Also in May, Mammoth Biosciences announced that it had signed a deal with GlaxoSmithKline to develop a CRISPR-based SARS-CoV-2 diagnostic test.