Delivering Better COVID-19 Diagnostics

KAUST-funded research initiative develops all-in-one COVID-19 testing kit

Testing, quarantine measures and vaccinations against COVID-19 are likely here to stay. Even as inoculation programs are being rolled out across much of Europe, the Middle East and North America, it is expected that the disease will remain a challenge in the years to come. Cases are high across many parts of the developing world, and public health experts have warned that the SARS-CoV-2 virus will eventually become endemic, meaning that it will continue to circulate in pockets of populations around the world for years to come. Influenza and the four human coronaviruses that cause common colds are also endemic, but acquired immunity and seasonal flu vaccines have rendered them manageable. Scientists still do not know if SARS-CoV-2 will follow the same path or if it will remain as deadly as it was in 2020 and 2021.

As such, tracking its evolution and the emergence of new variants is key. So too is continuing to develop more effective, efficient and affordable testing methods. KAUST-backed research has yielded one of the most dynamic all-in-one testing solutions to date. In 2020 Mo Li, an Assistant Professor of Bioscience at KAUST, was brainstorming ways to leverage his genetic engineering expertise to help combat the COVID-19 pandemic. Professor Li wondered whether a gene detection and sequencing approach called recombinase polymerase amplification (RPA) might be more useful – as well as faster, cheaper and more portable – than the polymerase chain reaction (PCR) approach commonly used for testing. He partnered with Juan Carlos Izpisua Belmonte, Roger Guillemin Chair at the Salk Institute for Biological Studies and Professor at the Gene Expression Laboratory, to find out.

PCR tests are the standard method to detect genetic material from the SARS-CoV-2 virus. If the sample is negative, however, patients and clinicians do not receive information on what may be causing the COVID-19-like symptoms. To do so, they must run separate PCR tests using different swab samples. Moreover, if the sample tests positive for COVID-19, it is unclear which variant is present. Another round of testing must be conducted, and this requires a large, expensive, next-generation gene-sequencing machine, which may not be available in all locations.

MO LI Assistant Professor of Bioscience

THE DESIGN OF THIS TEST IS REALLY FLEXIBLE, SO IT IS NOT JUST LIMITED TO THE EXAMPLES WE HAVE SHOWN. WE CAN EASILY ADAPT IT TO TACKLE ANOTHER PATHOGEN, EVEN SOMETHING NEW AND EMERGENT.

SALK INSTITUTE FOR BIOLOGICAL STUDIES

“The pandemic has provided two important lessons: first, test widely and quickly, and second, know your variants. Our NIRVANA method provides a promising solution to these two challenges, not only for the Covid-19 pandemic, but also for possible future ones.”

Juan Carlos Izpisua Belmonte, Roger Guillemin Chair and Professor at the Gene Expression Laboratory at the Salk Institute for Biological Studies

Unlike PCR tests, which cycle through lower and higher temperatures to separate and copy DNA strands, RPA uses proteins rather than temperature changes. The technology allows researchers copy longer lines of DNA, and probe for multiple genes at the same time. Professors Li and Izpisua Belmonte quickly realized that they could use this technique to not only detect COVID-19, but other viruses as well.

Backed by a competitive research grant from KAUST, and with assistance from physicians in hospitals affiliated with the Ministry of Health and several Saudi university partners, the team of researchers developed a small, briefcase-sized kit that, in a matter of hours, has the ability to not only test for COVID-19, but also identify the specific strain of the virus and simultaneously test for the presence of other viruses – such as influenza – with similar symptoms that may be mistaken for COVID-19. They call the method NIRVANA, an acronym for “nanopore sequencing of isothermal rapid viral amplification for near-real-time analysis”.

The scientists designed NIRVANA to test up to 96 samples for COVID-19, influenza A, human adenovirus and non-SARS-CoV-2 human coronavirus. In initial tests, the device reported positive and negative results within 15 minutes. Within three hours, the device finalized results on all samples, including the sequencing of five regions of the SARS-CoV-2 virus genome that are particularly prone to mutations, which can lead to new variants. Tracking this is especially important, as new variants could be vaccine-resistant. Additionally, the researchers tested NIRVANA on 10 samples known to be positive for COVID-19 and 60 samples of unknown SARS-CoV-2 status, as well as samples of municipal wastewater harboring SARS-CoV-2 and other viruses. In all cases, RPA was able to correctly identify which viruses were present. Moreover, the sequencing data also allowed them to determine the origin of SARS-CoV-2 in positive samples, differentiating strains from China and Europe, for instance. It is hoped that the machine can be commercialized to help fight the virus and ultimately save lives. With its small size and portability, it could be used for quick detection at schools, airports and seaports. It also could be used to monitor wastewater or streams for the presence of new viruses. Unlike existing detection and surveillance methods, NIRVANA does not require expensive infrastructure and can achieve what multiple tests and machines are currently required to do. NIRVANA is but one example of the innovative health care solutions being developed at KAUST, which continues to prioritize public health in the Kingdom and beyond.