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Scottish Researchers, Oxford BioDynamics Partner to Identify Epigenetic COVID-19 Biomarkers

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NEW YORK – Researchers at the University of Glasgow will use Oxford BioDynamics' EpiSwitch technology to uncover epigenetic biomarkers in patients suffering from COVID-19, the disease caused by the SARS-CoV-2 virus.

Scotland's Chief Scientist Office (CSO), a government health directorate, recently awarded roughly £1 million ($1.3 million) to researchers at the university as part of a £5 million funding call for research into COVID-19 announced by the Scottish government on March 25.

Nine projects altogether were funded, among them, "Viral and immunological correlates of clinical severity and response to anti-viral therapy for COVID-19," which is led by Carl Goodyear, a professor at the university's Institute of Infection, Immunity, and Inflammation.

The project's goals include identifying signatures that can predict the severity of disease in those infected, as well as determining how patients will respond to therapies.

Goodyear said that his team received £320,000 to support its work, which will involve about 300 patients enrolled in the Glasgow Early Treatment Arm favipiravir study, also funded through the CSO, which will evaluate the use of the antiviral favipiravir in patients hospitalized with COVID-19 in Glasgow-area patients. All of the projects funded through the call are expected to wrap up within six months.

"We will be taking in patients who come in and are suspected of being COVID-19 positive, recruiting them through the emergency departments, [and] potentially going into respiratory departments," said Goodyear.

Goodyear has been a long-time partner for Oxford BioDynamics (OBD), an Oxford, UK-based company that specializes in developing epigenetic biomarkers on its EpiSwitch platform. EpiSwitch relies on a variety of technology platforms, including microarrays and next-generation sequencing, to detect chromosomal conformation signatures, epigenetic biomarkers that represent an individual's gene-expression profile.

Goodyear has worked with OBD to discover biomarkers that can determine response to methotrexate, a drug sold by Pfizer that is commonly used to treat people with onset rheumatoid arthritis.

He wants to use the same approach to better understand changes in genetic regulation in COVID-19 patients, and to potentially develop tests for triaging patients as they come into emergency rooms, as well as guiding treatment decisions as to what therapy might be the best fit.

"From a clinical point of view, we still have no idea who will progress to the disease when they are infected," noted Goodyear. "People are talking a lot about different aspects, such as being male and obese," he said. "People are also talking about repurposing therapeutics, saying this is something we can use to treat people with at the moment, but we still don't know that precision medicine piece," he said. "How do we know who will progress and what they will respond to?"

Goodyear suggested that epigenetics might provide answers to those questions. "Different people have different epigenetic set points in their circulating immune systems," he said. "That influences sometimes how disease will progress and how they will respond to different therapies," he said. "We are really trying to capture that initial genomic aspect, to see how they will progress and how they will respond."

Other studies are also applying epigenetics to better understand COVID-19. Fluidigm said in March, for instance, that it was working with researchers at the Icahn School of Medicine at Mount Sinai to develop an epigenetic test on its microfluidics platform.

"It's clear from what's happening with COVID-19, there is an age range, and there is a presentation that sets one up for unfortunate outcomes and death," said Ewan Hunter, chief data officer at OBD. "Having a dysfunctional or disjointed immune system has an impact on that, and this is a very good way to look at what makes patients susceptible to outcome in the form of death," he said. "Our platform allows us to answer very difficult questions."

Goodyear said that though the new study is longitudinal, he hopes to develop biomarker signatures based on initial baseline samples. These could allow the researchers to already profile patients with EpiSwitch as they seek care, tipping off clinicians as to who might need admittance to intensive care.

"At least it will give clinical teams that information up front to say we are going to have to deal with this very seriously," said Goodyear. "It will help the NHS to know what will happen to the patient population coming in." They also hope to establish a signature for antiviral therapies.

"That will give proof of concept that in COVID-19 disease, you can find signatures that show if someone will respond to a therapy or not," he said. "It might get down to it, before we get a vaccine, that we need to stratify people for different drugs we think will work for them," Goodyear added. "If we had a battery of different tests you could run these."

The University of Glasgow is already set up to transfer any tests into a clinical setting. If successful, the study could therefore result in two epigenetic tests: one that flags those who will require intensive care and another that provides guidance on potential therapies.

OBD CSO Alexandre Akoulitchev said that in addition to yielding new tests, the study could also supply new understandings of COVID-19. "What we are trying to look at from the perspective of the EpiSwitch platform is specifically the deregulation of the immune system," he said. "For us, it's very important to understand the biology of deregulation," Akoulitchev said. "It gives us a better understanding of how to fight the virus and a better understanding of biology."

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