From Refining Tests to Tracing Its Path, an Innovative Yale Scientist Battles the Coronavirus

The United States and other developed nations got off to a standing start when the novel coronavirus began to emerge at the end of 2019, so it fell on universities, hospitals, and scientists to take their own measures to push back against what has become a pandemic. Yale got busy quickly, and one scientist who has been essential to that effort is Nathan D. Grubaugh, PhD, assistant professor of epidemiology (microbial diseases) at Yale School of Public Health.

Grubaugh, who came to Yale in 2018, has been instrumental in two vital Yale projects. The first, which required both speed and exacting accuracy, was to help validate assays for COVID-19 tests that were being implemented by the Yale New Haven Clinical Virology Lab. While CDC testing kits were becoming available by late February, vital reagents to help certify that the tests were accurate were not as widely disseminated. Marie-Louise Landry, MD, professor of laboratory medicine and of medicine (infectious diseases), and director of the lab, turned to Grubaugh’s research team to generate virus standards and controls that would help her to validate their test for emergency use authorization by the Food and Drug Administration (FDA).

“My group stuck to the challenge, and we went and found virus RNA from a group in Texas,” says Grubaugh. “Then, from that virus RNA, we were able to make pieces of that RNA that we can quantify to make in large batches and give to our hospital.” The FDA gave Yale permission to use its in-house coronavirus test on March 13, and it now is being used to test 400 patients and health care workers every day. “We have since sent these standards to dozens of labs and hospitals around the country and the world,” adds Grubaugh, “so that they can actually get their own assays up and running.” Testing is knowledge that can break transmission chains and may prevent countless cases of severe illness and death from COVID-19.

Mapping the pandemic

Grubaugh has also been using advanced tools to trace the spread of the novel coronavirus. The more that is known about its transmission and geographic distribution, the better the chances of taming the virus. In the past, Grubaugh had used genomic epidemiology, which traces the kinds of small mutations that all organisms produce, which are not harmful but are very useful for genetic detective work, to map mosquito-borne viruses such as Zika. The COVID-19 pandemic led him to drop his Zika work and apply its lessons to the coronavirus. Grubaugh got to work mapping the path of the novel coronavirus from its origins in Asia to patients here in Connecticut. In March, Grubaugh and colleagues posted a study on the preprint service medRxiv. “We found that the evolutionary history of the outbreak in Connecticut actually links it to the outbreak in Washington state. So, the virus has already been spread coast to coast in our country. And by looking at travel patterns and epidemiological patterns, we also see that there is higher likelihood now that the virus is being introduced into our region from other U.S. states than internationally. That should impact our policies.”

In fact, one could almost look at Grubaugh as prescient about the coronavirus outbreak. He was first author of a paper published in Nature Microbiology barely more than a year ago, in January 2019, that plots the course of a hypothetical coronavirus pandemic originating in the Florida Everglades. But it wasn’t prescience so much as the experience that he and his co-authors had amassed with Zika, Ebola, chikungunya, SARS, and pandemic H1N1, among other outbreaks. The novel coronavirus wasn’t even known when they wrote it. “We just wanted to get this information on paper while we were thinking about Ebola and Zika and before we were pulled away into something else,” Grubaugh explains. “We outlined how we would go through and use genomic epidemiology to investigate: to detect the virus, provide an early snapshot of where it came from, detail the transmission patterns, and overall show how it’s spreading around the world. And you’re seeing all of those steps now play out with how we are investigating this novel coronavirus.” Grubaugh says while certain ferocious aspects of COVID-19 symptoms were unforeseen, the patterns of its spread were not, and having mapped out a viral outbreak so recently has sharpened his thinking as he approaches COVID-19.

Learning even more

Now his work is turning to another aspect of the pandemic. “We have an Institutional Review Board approved research protocol with the hospital and we are enrolling inpatients to provide testing for research,” Grubaugh says. “We have also enrolled health care workers. We hope to do outpatient testing soon. So, all of the sequencing is second tier to our first goal of just testing patients and helping out our hospital.”

Though relatively new to Yale, Grubaugh is grateful for what he has found here, from the presence of a great teaching hospital where researchers are also clinicians who treat patients—and whose research is informed by their doing that—to the university’s extraordinary breadth of talent. “It really starts with the people and how committed they are to public health. It doesn’t matter if you’re on main campus working in molecular and cellular biology or ecology and evolution or if you’re on the med school campus in laboratory medicine or immunology,” he says. “There are so many different people who are very passionate about what they are doing and want to help. That makes it really easy to find people who know how to do things that you don’t know how to do.” He also praises his lab team and so many others for the 16-hour days they have devoted to this work. “None of this is possible without their commitment.”

It is a recipe for better times ahead.