By Deborah Borfitz
May 26, 2021 | Before COVID-19 came along, most people did not understand “presymptomatic” meant being contagious before exhibiting symptoms. They would scratch their head, wondering why they should care about a disease that had not yet made an obvious appearance.
Today the term is thrown into casual conversations around the dinner table, and large diagnostic companies are interested in producing products providing presymptomatic notice of infection with a pathogen, according to Ephraim Tsalik, associate professor in the departments of medicine and molecular genetics and microbiology at Duke University School of Medicine. Tsalik is also co-founder of Predigen, which has developed host response bacterial-viral (HR-B/V) tests that could offer that type of early warning system.
In a study newly published in Critical Care Medicine (DOI: 10.1097/CCM.0000000000005085), Tsalik and colleagues measured the host response to bacterial or viral infection in collaboration with a diagnostic platform developed by BioFire Diagnostics, owned by the French in vitro diagnostics firm, bioMérieux. The test was shown to differentiate bacterial and viral infections better than procalcitonin (the standard barometer) among 623 patients presenting in the emergency department (ED) with acute respiratory illness or suspected sepsis and did so in under an hour.
HR-B/V tests employ a gene expression method that has several advantages over current diagnostic strategies focused on identifying specific pathogens, says Tsalik. They are, for starters, more accurate, correctly identifying bacterial and viral infections 80% and 87% of the time, respectively, compared to the roughly 69% accuracy of procalcitonin.
They can also produce results quickly and without first identifying a suspected pathogen. That is because HR-B/V tests look for a distinct immune signal unique to the type of infection the body is fighting, he explains. A different set of genes is involved depending on whether the bug is bacterial or viral.
Last fall, results of a five-year study involving 1,465 patients was published in The Lancet Infectious Diseases (DOI: 10.1016/S1473-3099(20)30486-2), indicating a “previral” version of the host transcriptomic test could detect infections before clinical disease develops.
In another paper published earlier this year in Nature Communications (DOI: 10.1038/s41467-021-21289-y), the research team demonstrated considerable overlap between host gene expression in response to SARS-CoV-2 and a variety of other infections, but also found distinct features to distinguish between different viruses such as influenza and seasonal coronavirus.
The launch of the Molecular and Epidemiological Study of Suspected Infection (aka MESSI) study last summer marked the team’s pivot to examining whether the host gene expression test would work for patients with the pandemic virus, says Tsalik. When COVID struck, it was no longer sufficient to know if someone had a bacterial or viral infection without confirming if SARS-CoV-2 was present.
The team has separately been working with Biomeme on a test combining the measurement of host response to infection and detection of the culprit pathogen, providing more robust accuracy in test results and the potential to identify illness prior to symptoms. This collaboration takes advantage of Biomeme’s “PCR Anywhere” approach, offering a mobile, battery-operated system that delivers molecular diagnostics wherever they are needed.
In 2019, during the initial legs of the Antimicrobial Resistance Diagnostic Challenge run by the National Institutes of Health Division of Program Coordination, Planning, and Strategic Initiatives, Biomeme was Predigen’s teammate as finalists in the competition. The $19 million award ultimately went to Visby Medical (formerly Click Diagnostics) for a single-use test for detecting gonorrhea that includes assessment of antibiotic susceptibility.
Multiple companies have also expressed interest in measuring host response markers with the gene expression technology, says Tsalik, noting it is an area of “burgeoning development” for diagnostic testing and Predigen is one of few players in the space. “We are trying to get the test onto multiple platforms, so we can deliver host response content throughout the healthcare continuum—including hospitals, urgent care centers, emergency departments, and clinics—to improve the management of patients presenting with acute infection.”
Among the research projects underway are ones looking at host gene expression for sepsis diagnosis, sepsis risk, fungal, and tick-borne infections.
Ongoing financial support to develop the test and translate it into a commercially viable product has been provided by the Antibacterial Resistance Leadership Group (ARLG), which is in turn funded by the National Institute of Allergy and Infectious Diseases, says Tsalik. The company just learned it is being awarded a $4 million grant from the Department of Defense to continue developing two tests on the diagnostic platform developed by Biomeme—one to identify presymptomatic viral infection and another to discriminate bacterial from viral infection, says Tsalik.
Patients and clinicians routinely grapple with the kinds of questions HR-B/V tests are designed to answer, Tsalik says. Coupled with telemedicine, they will be a huge enabler of decentralized care, he predicts.