Dartmouth labs put Covid-19 research on the fast track

Coalition of scientists is working around the clock to improve testing and develop new therapies
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David Leib, professor of microbiology and immunology at the Geisel School of Medicine, and research scientist Audra Charron are working with other Dartmouth researchers to validate a new and improved test for the novel coronavirus. (Photo courtesy of David Leib)

As the novel coronavirus takes its deadly toll, there’s potentially life-saving activity going on night and day at Dartmouth College in Hanover.

“Whether developing or deploying new testing strategies, laying the groundwork for antibody-based therapeutics, or contributing personal protection equipment, the Dartmouth research community is already making the fight against this novel coronavirus our own,” says Dean Madden, vice provost for research.

Among them is David Leib, a virologist and professor and chair of microbiology and immunology at the Geisel School of Medicine, who is working with colleagues across campus, around the country, and the world to validate a new and improved test for the disease caused by the coronavirus. He is married to Audra Charron, the lead scientist for the lab’s Covid-19 diagnostic validation study. Results from the study are already coming in and look very promising. As a result the work is moving toward emergency FDA approval and use in the clinic.

“It’s taken the U.S. a long time to wake up to this crisis and now we’re playing massive catch up,” says Leib. “There’s an enormous backlog of people that needed to be tested, and what we’re now learning is that we actually should be testing asymptomatic individuals as well those with symptoms. Really and truly, in a pandemic of this nature, rigorous, rapid and open access to testing is key.”

But Leib says two major obstacles stand in the way of safer, more effective, more widespread testing. The test, currently approved by the federal Food and Drug Administration, relies on an extraction agent, which isolates the RNA of the virus. Those agents are in short supply, Leib says.

In addition, kits are in short supply, and current testing takes about seven hours, and for testing patients during hospital intake, time is especially of the essence.

Fortunately, says Leib, a company in California is attacking those problems: At Atila Biosystems, CEO Youxiang Wang has developed a new test that could be a powerful weapon in the fight against Covid-19.

“Wang’s test is unique because it eliminates the need for an extra step to extract RNA from the virus, “says Leib. “It’s also unique in that it’s very rapid, taking less than an hour to get results. It is also sensitive, simple, relatively cheap, and provides some advantages of safety for the testing staff.”

But it hasn’t yet been compared head to head with the FDA-approved CDC test now in use. That validation is now being done in Leib’s lab by Audra Charron.

“Working alone, because of social distancing requirements, she’s performing real-time reactions using the kit from Atila on purified Covid-19 viral RNA and blinded clinical specimens obtained from Joel Lefferts at the Dartmouth-Hitchcock clinic,” says Leib.

Charron is testing three kinds of samples. Some are from patients who tested positive for Covid-19; others who have a different virus; and still others are from healthy people. “We do not know which samples are from sick, and which from healthy patients, and we run those specimens through the Atila test. We then un-code the samples and compare the Atila test with CDC test to see if the results match,” says Leib. “We’re really testing one test against another.”

Leib says universities across the world are banding together in efforts like these.

His lab has joined an international, interdisciplinary coalition founded by a nonprofit group based in Israel. Besides Dartmouth, members include the Cleveland Clinic and the Medical College of Wisconsin. “We’re getting enormous help from Geisel, D-H and the provost’s office,” says Leib. “They’ve helped us to scale regulatory hurdles to keep us on a fast track.”

Partnering With the NH state lab

Another team from Geisel and Dartmouth-Hitchcock Medical Center has been improving diagnostic methods currently in use locally.

Gregory Tsongalis, a professor of pathology and laboratory medicine and director of the laboratory for Clinical Genomics and Advanced Technology, says the New Hampshire State Lab was initially overwhelmed with the demand for tests, so D-H verified a high throughput automated test from Abbott laboratories, which is now being used to reduce the state’s backlog and test all D-H patients.

“We were fortunate to be ahead of the curve with respect to developing internal testing capabilities. We started with the same test as the state lab that was developed by the CDC, and they provided us with positive and negative samples so we could verify testing here at Dartmouth. We have been in close communication with the state lab throughout this process. Our automated testing capabilities allow us to test up to 1,000 samples in 24 hours. Because of this, we are available to help the state lab with any overflow of samples they may need us to test, and we can now begin to accept testing from other facilities,” says Tsongalis. “We are now running more tests per day than we did in the first week with the system we have in place.”

Hope for treatment

On the therapeutic front, researchers from the Thayer School of Engineering at Dartmouth are investigating whether the antibodies that help some people recover from the virus can be turned into medicine for other patients. Jiwon Lee, the Ralph and Marjorie Crump Assistant Professor of Engineering, is an engineer who focuses on the human immune system.

“My lab focuses on developing new technologies that allow us to take blood from people whose immune systems have successfully fought off an infection, and determine the amino acid sequences of the different antibody molecules in the blood,” says Lee. “For COVID-19, for example, knowing the antibody sequences enables us to test and determine which antibodies are the most effective at neutralizing or preventing the infection.”

Collaborating with a group of clinicians, scientists and engineers from Dartmouth and the University of Texas at Austin, Lee says his lab is trying to understand antibody responses to Covid-19 and identify antibodies with therapeutic potentials.

In the meantime, he and other Dartmouth researchers are taking the utmost precautions to stay healthy.

“We just cannot get sick,” Lee says. “And we cannot delay.”

Meanwhile, Dartmouth donors are also stepping up, says Vice Provost Madden, “providing rapid support to a new series of urgent, high-impact studies of the virus and its impact across our communities.”

Charlotte Albright works in the Office of Communication at Dartmouth College. This article originally appeared on Dartmouth’s website.

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