According to medical researchers, major breakthroughs in blood testing technology that use immune system response and genetic analysis to identify disease quickly and cost-effectively will be on the market within a few years.
Shannon Fernandes, Tayah Fernandes’ mother, realised her four-year-old daughter was seriously ill one morning last May and rushed her to the nearest emergency room in Manchester, England. The coronavirus had arrived on British soil weeks before, and doctors were initially unsure how to treat Tayah’s symptoms, which included stomach pains and a bright red rash.
They gave her antibiotics for a possible bacterial infection, but her condition worsened, with her fever skyrocketing. This was the ultimate medical nightmare for her parents, or any parents; doctors were in the dark for days about the cause of their daughter’s illness.
Following additional blood tests, doctors determined that Tayah was suffering from an unusual inflammatory syndrome that paediatric infectious disease specialists had only recently begun to see, but suspected had links to Sars-COV-2.
Young patients in the United Kingdom and the United States were arriving in intensive care units with symptoms similar to another disease known to doctors as Kawasaki. However, there was no guarantee that the same course of treatment — injecting a solution of donors’ antibodies into the bloodstream — would be effective.
Tayah’s parents were relieved when the antibodies solution, known as immunoglobulin, worked. However, around the same time last May, a team of Imperial College London researchers confirmed, through complex analyses of blood samples taken from patients like Tayah, that this was, in fact, a new disease distinct from Kawasaki.
A related breakthrough in that same laboratory, focused specifically on the behaviour of individual genes, could have seismic implications for a multibillion-dollar diagnostics sector that has received unprecedented attention from patients, regulators, and the business world during the course of this pandemic.
A new method for identifying a specific illness from blood samples is based on a correlation between the activity of a small set of genes, which represents the immune response, and specific pathogens that cause a specific disease — just as the poliovirus causes polio, so does the coronavirus (SARS-COV-2, a pathogen) cause Covid-19. Scientists believe that by studying a small number of genes, they will be able to quickly determine which pathogen is in a patient’s system, what disease they have, and how to best treat them.
Companies ranging from small research university spin-offs to industry behemoths like Abbott Laboratories and Danaher’s Cepheid are attempting to build on two decades of research into how our own immune systems naturally respond to foreign substances in our bodies, such as pathogens like bacteria or viruses. Current technology, such as Cepheid’s GeneXpert technology, can differentiate between the different RNA of various viruses, such as SARS-COV-2 or a specific influenza strain, but experts say it’s becoming increasingly clear that our bodies’ immune systems can be faster, more accurate detection systems.
Traditionally, doctors had to rely on a patient’s case history and symptoms to determine the cause of an illness and develop a treatment plan. Recently, molecular laboratory inspections, such as the Cepheid technology, have enabled clinicians to identify specific pathogens in nasal mucus, throat swabs, or blood samples that may have caused an illness. However, searching for bacteria or viruses in this manner can be time-consuming, expensive, and sometimes simply ineffective. A virus’s specific RNA signature can be difficult to detect.
Abbott and Cepheid did not respond to requests for comment.
The Imperial College London team, working independently but concurrently with several counterparts around the world, is now convinced that future diagnoses can soon be performed using table-top tests that take only a few minutes.
These tests would not explicitly screen for a specific pathogen, but would instead allow scientists and medical professionals to simply observe how specific genes in the body are behaving as an indication of how an immune system is already responding to a pathogen that would otherwise be difficult to detect.
Mike Levin, an Imperial College professor, is currently leading a European Union-funded study on this potential, dubbed “Diamonds.” In recent years, he and other researchers have demonstrated how observed activity in a small number of our genes can serve as a kind of shorthand for our body’s immune response to a pathogen. If a few specific genes are seen to be activated — or, conversely, inhibited — in a blood sample, it can indicate that a person is preparing to fight off a specific pathogen.
Levin and colleagues have already demonstrated proof of concept for this diagnostic approach in studies involving thousands of tuberculosis patients and hundreds of Kawasaki patients. And his Imperial College team’s work with the “Diamonds” study is beginning to bear fruit, which could aid in identifying the distinct immunological markers of illnesses such as the coronavirus-linked multi-system inflammatory syndrome in children like Tayah Fernandes, now known as MIS-C.
When Covid-19 was discovered in multiple locations, trailed by MIS-C, Levin and his colleagues were given an unprecedented opportunity to test this technique on an entirely new disease.
In the future, these tests should be able to produce multi-class results rather than just binary results by relying on massive amounts of data and machine learning. This means they could determine not only whether a pathogen is bacterial or viral, or whether someone has a specific disease, but also which of a plethora of illnesses is afflicting their patient.
In short, Levin anticipates that by studying the behaviour of a relatively small number of genes, clinicians will be able to classify patients into all major disease classes within an hour.
“We believe this is a completely novel approach to medical diagnosis,” Levin said. He believes the research will serve as the foundation for new technology, but he has no financial stake in any business that stems from it.
Rather than the “stepwise process” of first eliminating bacterial infections, then treating for the most common conditions, and then doing more research, “this idea is that the very first blood test can tell you whether the patient has an infection or not, and what group of infection that is, right down to the individual pathogens.”
According to Purvesh Khatri, an associate professor at the Stanford Institute for Immunity, Transplantation, and Infection and the Department of Medicine, our immune systems have been evolving for millennia to combat pathogens, so studying our bodies’ responses may be more effective and efficient.
“Until now, we didn’t have a technology that could measure a set of genes at the point of care,” he explained. “However, in the last few years, there have been enough technologies available that allow us to measure a few genes in a rapid multiplex point of care assay.”
While neither the FDA nor European regulators have approved gene-based pathogen detection systems, Khatri, who is assisting in the launch of a related commercial venture, believes they will be available soon. “Several will be available on the market within the next year or two.”