A sinister intruder, the coronavirus known as SARS-CoV-2 infects the body in the same way other viruses do—by hijacking healthy cells and forcing them to create copies of the virus. But this virus has a secret weapon: spiky surface proteins that easily bind to cells in the lungs, making the lungs especially susceptible to infection.
As the lungs fight the virus, the body’s immune system triggers inflammation to help defend against the intruder. While lung inflammation can cause breathing difficulties, most people recover from COVID-19. But in the most serious cases, the body’s immune system may go into overdrive, causing widespread inflammation that can damage lung tissue.
This can lead to acute respiratory distress syndrome (ARDS), a life-threatening injury that allows fluid to leak into the lungs, causing extreme breathing difficulties. With no cure for ARDS, physicians can only offer patients supportive care, often using a ventilator to assist breathing in hopes that the lungs will eventually heal.
Breathing in hope
Physician-scientist Holger Eltzschig, MD, PhD, has studied ARDS for nearly two decades. In a 2013 preclinical study, his team found that a specific protein can help protect the lungs by reducing inflammation and fluid buildup during ARDS. Now, in partnership with clinical expert Bentley J. Bobrow, MD, the team is on the precipice of unlocking an innovative treatment that activates this protein to treat ARDS in patients with COVID-19.
With Bobrow serving as principal investigator, the team is leading a randomized clinical trial to determine whether an investigational oral drug called vadadustat—which activates the protective protein—can help COVID-19 patients with ARDS. Although vadadustat, created by Akebia Therapeutics, is currently in development to treat patients with anemia of chronic kidney disease, Eltzschig quickly recognized its potential to defend against one complication of COVID-19.
“All of my lab’s research in ARDS over the last 20 years has led to this moment,” says Eltzschig. “Dr. Bobrow and his team’s expertise in leading clinical trials allows us to translate this research into a therapy for patients who need it most.”
With help from the UTHealth COVID-19 research task force, the team organized the clinical trial in three short months—a feat that ordinarily takes longer than a year. The team will enroll up to 400 patients with COVID-19 who require supplemental oxygen in the randomized trial, with patients receiving either vadadustat or a placebo. In August 2020, the team enrolled the first patient.
“Every day in the Department of Emergency Medicine, we see patients who are critically ill with COVID-19—oftentimes they are only hanging on with help from a ventilator,” says Bobrow. “That motivates our team to work at warp speed to develop better treatments.”
The trial, initially funded by UTHealth Center for Clinical and Translational Sciences and Akebia Therapeutics, began at Memorial Hermann Health System and will be expanded to other sites across the United States if the team sees promising results. In September 2020, the team received a $5.1 million grant from the United States Department of Defense, recognizing the trial’s potential to help protect military personnel from ARDS.
“ARDS is proving to be one of the greatest challenges of the COVID-19 pandemic, but we have the people and ideas to overcome it,” says Bobrow. “This trial is a product of the incredible research and collaborations happening at UTHealth, and a prime example of why we are positioned to tackle a wide variety of health challenges.”
The next generation of researchers
Although ARDS can be a serious consequence of the virus, Nathan Berg, a student in the MD/PhD program at McGovern Medical School at UTHealth and The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, remains hopeful that his research in acute lung disease will make a difference.
“At the onset of the pandemic, I knew our work in acute lung injury would have the opportunity to help find a solution to ARDS,” says Nathan. “This is what we study every day, and now we have a chance to apply our research to help people with COVID-19.”
Under his mentors, Eltzschig and Xiaoyi Yuan, PhD, Nathan has dedicated his entire graduate education to studying acute lung injury, a result of ARDS.
“My main research interests include harnessing the protective properties of lung cells to defend against lung injury and finding ways to subdue the overactive immune system response to lung injury,” Nathan says. “Breakthroughs in these areas could lead to better therapies for people who suffer from deadly lung injuries, such as ARDS caused by COVID-19"
“Being part of the MD/PhD program during the pandemic has shown me the importance of being able to translate research from the lab to the bedside to help patients who need it most,” he says. “Pathogens like COVID-19 are among the biggest threats to health. As I grow in my career as a physician-scientist, I want to continue searching for ways to help us overcome them.”
A CATALYST AMID CHAOS
With the urgent need to understand the virus and develop evidence-based therapies, UTHealth created a task force on COVID-19 research. The task force, led by Charles C. (Trey) Miller, PhD, brings together experts from all six schools to ensure effective collaboration for COVID-19 research.
“While COVID-19 has upended life across the world, it has catalyzed our efforts to get things done quickly and efficiently,” says Miller. “The COVID-19 research task force allows us to rapidly streamline studies, mobilize resources, and coordinate teams across the institution.”
Following its first meeting in March 2020, the task force focused its efforts on four areas: creating a cohort study of COVID-19 patients who interact with UTHealth providers, coordinating informatics to link electronic health data with artificial intelligence tools, reviewing clinical trials, and establishing
“With the largest clinical practice in the city, a thriving research community, and our top-tier UTHealth School of Public Health, our university is well positioned to lead the response to the pandemic, in our community and beyond,” says Miller. “Our infrastructure will enable us to respond to the long-term impacts of this virus, even after the pandemic subsides.”
The Research Accelerator Fund—the university’s crowdfunding initiative to tackle the most pressing health needs—will continue to give UTHealth leadership flexible resources to support high-impact projects that address the pandemic and future health challenges.
To join the response to COVID-19 by supporting the Research Accelerator Fund, visit go.uth.edu/raf.
A HIGH-STAKES BALANCING ACT
Contact tracing can help slow the spread of COVID-19 by identifying and following up with individuals who may have encountered an infected person, yet the number of positive cases must remain close to 200 cases a day in order for contact tracing to be effectively employed. Using technology can help bridge this gap. Mobile smart devices with GPS technology offer a promising platform to help trace the real-time location of users; however, privacy concerns prevent many people from embracing contact tracing applications.
Through balancing privacy protection and public health utility, two researchers at UTHealth School of Biomedical Informatics, Xiaoqian Jiang, PhD, and Amy Franklin, PhD, developed a contact tracing app to help reduce the spread of COVID-19.
“We believe that privacy is a fundamental human right, even during a pandemic,” says Jiang. “Our contact tracing app allows users to control how often the app collects information and how much information it collects, helping to preserve privacy while also reducing infection risks.”
The app, called Real-time Contact Tracing and Risk Monitoring (REACT), tracks user locations and symptoms. When a user encounters someone who has COVID-19, the app alerts the user. REACT also enables users to monitor their own risks based on the locations they visited and the aggregated risks of other users they have encountered. Additionally, it can detect early signs of community spread to help prepare for larger-scale infections.
“Unlike other apps that use GPS and Bluetooth to track users at all times, REACT only logs when a user contacts another user, and it employs privacy protection techniques to obscure the location of the contact,” explains Franklin.
REACT is a product of Jiang and Franklin’s collaboration with researchers from the University of Southern California and Emory University to harmonize strengths and compare different architectures and solutions to deliver the best performance and usability. Together, the team received a COVID-19 research grant from the National Science Foundation to develop the app.
“The University of Southern California team is skilled in mobile data anonymization, the Emory group is renowned for their work in de-identifying data, and we have expertise in designing models that preserve privacy,” says Jiang.
The team released REACT in December 2020. Visit www.cs.emory.edu/site/react to learn more or download REACT.