More than 700 faculty, staff and students tuned into the Duke University School of Medicine’s first COVID-19 Research Forum, held virtually on Friday, April 17, 2020.
The goal of the event was to highlight important work, share knowledge, discuss opportunities and encourage partnerships and collaboration among researchers.
Thirty faculty members from across the school gave talks throughout the day, which were organized into panels focused on the biology of the virus, how it spreads and evades the human immune system, development of a vaccine and therapeutics, and measures taken at Duke to offer the best care for COVID-19 patients and safety for healthcare workers.
Keynote talks were given by Chris Woods, MD, professor of medicine and global health, and Bart Haynes, MD, Frederic M. Hanes Distinguished Professor of Medicine and director of the Duke Human Vaccine Institute.
“This is going to be an illuminating and engaging day. It’s a great opportunity for all of our scholars at Duke to share ideas and insights. What we hope will emerge from this are new and exciting approaches to what we consider to be one of the biggest challenges in science today,” said Mary E. Klotman, MD, dean of the Duke University School of Medicine, in her opening remarks.
Woods, an emerging infection researcher, kicked off the faculty research talks by giving an overview of the spread of COVID-19, moving from the first cases detected in Wuhan, China in December 2019 to its current infection in April 2020 of more than 2 million people worldwide.
Sharing a One Health diagram first developed in 2003, Woods explained how humans’ increased contact with animals, both wild and domestic, allows for viruses to more easily spread. Increased global travel, urbanization, agricultural practices, and human encroachment on formerly ‘wild’ ecosystems are all drivers of disease emergence.
“As an emerging infections epidemiologist, I’ve been tossing around warnings for the coming plague now for decades but I have to admit, somewhat sheepishly, that I don’t think I ever really believed we would be here. It is a remarkable time, unprecedented in scope,” said Woods.
Woods shared information about the local outbreak, stating that there are more than 5,000 COVID-19 cases in North Carolina, with more than 100 deaths and approximately 450 people hospitalized as of April 17. However, social distancing measures have drastically decreased the rate of transmission.
“We’re successfully flattening the curve and we are approaching our maximum number of hospitalizations,” said Woods.
Woods highlighted multiple studies and clinical trials taking place at Duke to develop better treatment, including participation in the NIH-supported clinical trial of the drug remdesivir previously used during the Ebola outbreak; a partnership with Veterans Affairs to clinically test a hydroxychloroquine and antibiotic Zithromax (commonly known as Z-Pak) combination, and the Healthcare Worker Exposure Response and Outcomes (HERO study), which evaluates hydroxychloroquine’s effectiveness in preventing infection in healthcare workers.
Woods’ own study, Molecular and Epidemiological Study of Suspected Infection (MESSI), involves collecting biological samples from enrolled patients with suspected COVID-19 in order to generate improved understanding of natural history, transmission, antibody, and risks for disease progression, he said. He is recruiting participants from the local community, including emergency departments, inpatient doctor’s offices, and intensive care units, and specimen collection includes close contacts and pets of the patient in order to better understand transmission.
After Woods’ overview, a panel of virologists from the Departments of Molecular Genetics and Microbiology, Immunology, and Pediatrics moved from the big picture to the ‘small’ picture, sharing images taken of Sars-CoV-2 using an electron microscope.
“When you look at the virus under the electron microscope, it has a corona-like halo such as what you might see during a solar eclipse,” said Stacy Horner, PhD, assistant professor of molecular genetics and microbiology (MGM). She and other panelists, including Nicholas Heaton, PhD, assistant professor of MGM, Micah Luftig, PhD, associate professor of MGM, and Sallie Permar, MD, PhD, Wilbert C. Davison Distinguished Professor, described how the virus enters the cell, replicates its genome in the cell and promotes expression of its genes, and ultimately changes the biology of the cell in order to replicate.
Next, a panel of immunologists—including Horner; Georgia Tomaras, PhD, professor of surgery; Ed Miao, MD, PhD, instructor of immunology; Ashley Moseman, PhD, assistant professor of immunology; and Amanda MacLeod, MD, associate professor of dermatology and assistant professor of immunology and molecular genetics and microbiology—described how the virus interfaces with the innate and adaptive immune systems, including how it evades detection by the innate immune system early in infection, and how it invades through specific ports of entry: the nose and the skin.
A session devoted to discussion of therapeutics screening included talks by Kevin Saunders, PhD, associate professor of surgery, and Priyamvada Acharya, PhD, associate professor of surgery. They discussed how solving the structure of the spike protruding from the virus particle using the Titan Krios cryo-electron microscope on Duke’s campus could aid therapeutics development.
Another panel moderated by Francis Chan, PhD, professor of immunology, highlighted lessons learned from the lab and clinic, including how the virus manifests in the lungs and cardiovascular system, why people lose their sense of smell, and the role that genetics plays in resistance to the disease.
Yet another panel, moderated by Hashim Al-Hashimi, PhD, James B. Duke Professor of Biochemistry, focused on the development of better tests for COVID-19, counter measures to help the infected until a vaccine can be developed, and better environmental screening.
Michael Datto, MD, PhD, associate professor of pathology and medical director for Duke University Health System Clinical Laboratories, said that of the approximately 11,500 tests his team has processed locally, six percent have been positive. Furthermore, of approximately 1,200 patients being screened prior to scheduled surgical procedures at Duke, only five tested positive and of those two were confirmed to be asymptomatic at the time of testing. This provides “an interesting window into the prevalence of this disease in our state,” he said.
Tom Denny, MSc, MPhil, professor of medicine, has been testing blood samples from COVID-19 patients to determine when and how antibodies—the warriors that the immune system creates and dispatches to fend off invaders—are produced to protect against the virus. He wants to know how this naturally-occurring process might be harnessed and amplified to help people fight off the virus better and more quickly.
In order to test guidelines meant to protect hospital workers and visitors, Greg Gray, MD, has been sampling air columns in the hospital rooms of COVID-19 patients to determine if SARS-CoV-2 can project through the air beyond the six-foot rule.
“We can learn quite a bit in a non-invasive way,” said Gray.
However, all of these prevention techniques and counter measurements are in lieu of a vaccine being developed that could more widely and powerfully protect against the onset of infection.
In the final keynote talk of the day, Haynes, a virologist with more than 30 years of experience in vaccine development, shared information about Duke’s rapidly evolving attempt to create a vaccine. Haynes’ team is just one of 70 teams around the world trying to find a vaccine, he said.
As with most vaccines for RNA viruses, including the annual flu shot, development hinges on one’s ability to predict how the virus will mutate by the time the vaccine is administered. Sars-CoV-2 is no exception in terms of its ability to mutate, said Haynes, however right now its rate of mutation is determined to be 26 changes per year versus the 120 changes that the flu virus averages. Generally, prediction of RNA virus strains is based on a variety of data sources including the results of surveillance, as well as laboratory and clinical studies over the past year.
Although an extremely difficult process, vaccine development is crucial.
“The COVID-19 pandemic will continue at some level until a safe and effective vaccine is available,” said Haynes.
Attendees of the symposium expressed thanks to Duke scientists, clinicians, and front-line health care workers for their COVID-19 response and efforts. Colin Duckett, PhD, vice dean of basic sciences in the School of Medicine, spearheaded the forum and said he was proud of Duke researchers’ quick response to the pandemic, which was showcased throughout the day.
“It showed the spectrum of our efforts from basic, fundamental virology, to understanding the immune response, all the way through to the treatment of our patients,” said Duckett.
“I have felt from the beginning of COVID-19 that this is really a defining moment for the missions of academic health systems,” said Dean Klotman. “It really is going to be the convergence of excellent health care, education, and science that is ultimately the solution.”