Using Epigenetic “Fingerprints” to Identify Coronavirus Infections

October 7, 2020 | Michaela Kane

In a DARPA-funded project, Duke BME’s Xiling Shen and collaborators across the U.S. are designing a diagnostic test that aims to identify coronavirus carriers early and predict the symptom severity

This illustration, created at the Centers for Disease Control and Prevention (CDC), reveals the structure of the coronavirus.

The most common diagnostic tests for coronavirus involve a nasal swab that tests for the presence of the virus in the upper respiratory tract, or an antibody test, which identifies if a patient has developed antibodies to the virus. The nasal swab is often a hit-or-miss as it takes weeks to develop antibodies after the onset of infection.

But Xiling Shen, the Hawkins Family Associate Professor of Biomedical Engineering, Chris Woods, MD, the chief of the infectious disease division and associate director of the Center for Applied Genomics and Precision Medicine, and a team of collaborators at Mount Sinai hope to address this problem by developing a new diagnostic test to identify carriers of the coronavirus before they become contagious and spread the disease and to predict whether their symptom will be severe enough to require ICU care.

“The current diagnostics for COVID-19 mainly focus on detecting the virus’s DNA or virus antibodies, both of which can take days or weeks to develop in large enough quantities to measure,” says Shen. “Rather than look for these specific viral markers, we wanted to develop a test that looks for more immediate changes in our own immune system as the body responds to a coronavirus infection.

“These changes take place as early as 24 hours after the virus enters the system, and right now our understanding is that a carrier isn’t contagious until several days after infection. We’d also be able to use these changes to identify if a case is more likely to progress to a severe infection.”

Xiling Shen

The diagnostic was developed through MEMENTO (Mapping Epigenetic Memory of Exposure to Observe), a project supported by the Defense Advanced Research Projects Agency’s (DARPA) new Epigenetic CHaracterization and Observation (ECHO) program. Launched in September of 2019, ECHO aims to support researchers as they build a field-deployable device that can test small biological samples––like a drop of blood or a nasal swab––for evidence of epigenetic changes that reveal a detailed history of an individual’s expose to dangerous materials or pathogens.

After the global explosion of coronavirus cases in early 2020, the research teams focused on adapting this work to address the growing pandemic.

“Dr. Chris Woods and his team collected blood samples from patients who had tested positive for the coronavirus,” says Shen. “Rather than just collect samples from patients in the ICU, they collected samples from individuals who were exposed to the virus but remained asymptomatic and from patients who only developed mild symptoms and never needed to go to the hospital.”

“They took samples on the day of diagnosis, three days out, a week out, two weeks out and three weeks out, which allowed them to track the disease progression and gave us the power to explore if there were certain signs about patients that may progress to a severe disease,” he says.

Shen and his team in Duke’s Center for Genomic and Computational Biology then analyzed the samples for epigenetic changes to the cells in the immune system.

“When we say we’re looking for epigenetic changes, we’re essentially looking for a modification or a ‘fingerprint’ on the cell, which indicates when the cell has responded to external stimuli,” says Shen. “We can see if an individual cell has sensed a threat, or if it has energized itself to fight a virus. We also know that certain cells, like immune cells or blood cells, respond to COVID-19 very specifically, and our single-cell technology allows us to track how certain cell types respond out of a wider population.

Shen and his team used these epigenetic fingerprints to identify potential biomarkers for coronavirus infection and signals for a more severe infection. Working with DARPA and industrial partners, the team hopes to rapidly implement these biomarkers into clinical diagnostic platforms.

“Our collaboration with DARPA gives us a direct path towards clinical applications and expedited FDA approval,” says Shen. “If this test is approved, we’d be able to let people know that they’re infected days earlier than the current standard. We’re excited about its potential to fill a big gap in testing.”