Blood-based test IDs viral infection before symptoms appear
A team of scientists at Duke Health has identified biomarkers that accurately detect viral infections before a person becomes symptomatic. The findings, published in The Lancet Infectious Diseases, could have broad potential for slowing, treating and managing infectious disease outbreaks and pandemics.
The blood-based test uses a gene expression assay to predict the presence of nine respiratory viral infections, including influenza, enterovirus, adenovirus and coronaviruses, which include common colds. To develop the assay, scientists looked at tens of thousands of genes to see how they react in a given situation and used machine learning to reveal patterns, or signatures, in the data. They were able to identify distinct gene expression signatures for both viral and bacterial infection.
Scientists from Durham, N.C.-based startup Predigen Inc., who maintain academic positions at Duke University, were involved in the design and execution of the study. A 2016 Duke spinout, Predigen has licensed the diagnostic biomarkers from the school and is developing tests for clinical use.
“This study is exciting because, currently, there is no reliable way to identify presymptomatic patients,” said Ephraim Tsalik, co-founder and chief scientific officer of Predigen and associate professor of medicine at Duke, who was also a clinical investigator in the study. “Early diagnosis can lead to earlier, more effective therapy as well as quarantine before someone can spread the infection to others.”
For the study, the researchers enrolled 1,465 Duke students between Sept. 1, 2009, and April 10, 2015, and monitored them over the course of each school year for the presence and severity of eight symptoms of respiratory tract infection. The students completed a daily web-based survey, rating their symptoms on a scale of 0-4.
Index cases were defined as participants who reported a six-point rise in cumulative daily symptom score. Biospecimens were collected from 264 index cases with reported symptoms of disease, 150 of whom had a viral cause confirmed by real-time polymerase chain reaction (RT-PCR) assay.
The researchers also monitored 555 close contacts of the sick study participants who were enrolled in the study. Of those, 162 showed signs of respiratory tract infection and 106 were confirmed to be sick using PCR testing.
According to the researchers, the transcriptomic assay predicted viral infection as much as three days before the disease was full blown and often before any symptoms or detectable viral shedding occurred.
“While our study was conducted prior to the COVID-19 pandemic, our data show that these biomarkers of viral infection are present and detectable before clinical disease develops and thus could form the basis of novel approaches to early identification and management of emerging viral outbreaks and pandemics,” said Micah McClain, associate professor in the Department of Medicine at Duke and lead study author.
Partnership with Biomeme
Predigen is partnering with Biomeme Inc., of Philadelphia, to deliver host response tests to the point-of need, applying Predigen’s tests to Biomeme’s “PCR anywhere” platform.
“Duke has told us what we need to measure (discovery). Predigen is working on how we measure it (implementation),” Tsalik told BioWorld. “The joining of Biomeme’s rapid PCR technology with Predigen’s host response content establishes an end-to-end solution with considerable upside for precision medicine.”
Biomeme’s 27-target, multiplex, quantitative RT-PCR assay yields results in about an hour. The gene expression signatures and algorithms have been combined in a point-of-need prototype using Biomeme’s Franklin thermocycler and companion mobile app.
“Although this test can detect presymptomatic viral infection, it is also a highly accurate test for viral infection in symptomatic patients,” Tsalik said. “Patients often seek care for vague symptoms that could be due to viral infection, bacterial infection, allergies, asthma or many other possibilities. The test described in this study could also help identify a viral infection as the cause of those symptoms.”
Predigen is in the process of finalizing the viral infection test and another test identifies the presence of bacterial infection. Once finalized on the Biomeme platform, it will start clinical studies to support U.S. FDA clearance and commercial launch.
COVID-19 and beyond
“The Biomeme platform has already received EUA [emergency use authorization] approval for the detection of SARS-CoV-2, so we will build on that success to rapidly commercialize this groundbreaking host response test,” Tsalik said.
Predigen’s plans include a host response test for bacterial vs. viral infection, as well as the specific detection of SARS-CoV-2. “Our hope is to accelerate the test’s development so it can have a positive impact on the pandemic,” Tsalik said.
The company currently is capable of producing tens of thousands of tests per week. With FDA clearance or EUA, it would move quickly to scale up to meet demand, he added.
The pathogen-agnostic approach demonstrated in the Lancet study could have real value in future pandemics involving novel pathogens. It could also help to curb the unnecessary use of antibiotics, a major source of antibiotic resistance, by quickly ruling out bacterial infection.