On a Mission to Understand COVID-19

Researching for Answers

A multidisciplinary group came together with one goal: understanding COVID-19

Gyongyi Szabo, MD, PhD led BIDMC research on understanding COVID-19Gyongyi Szabo, MD, PhD, thrives under pressure. As a globally renowned expert in liver immunology and Chief Academic Officer of BIDMC and Beth Israel Lahey Health (BILH), Szabo is accustomed to tackling one challenge after another. But the pandemic's sudden onset demanded a level of problem-solving beyond anything she—and her expert team—ever could have imagined. “It was like a hurricane struck, but we worked as a team to overcome every barrier we were faced with,” Szabo remembers.

Just as clinical care underwent a radical transformation at the outset of the pandemic, so too did research. “Massachusetts' statewide lockdown mandated that all of BIDMC's hundreds of basic research laboratories had to cease operations,” says Andi Hernandez, Vice President of Research Operations. “It was an emotional time. Dozens upon dozens of our scientific staff were putting their longtime experiments on pause, knowing they might lose years of work.” But, she adds, there was absolutely no hesitation—each member of the research community worked together as they reconfigured their scientific plans. “Everyone understood that this heartbreaking decision was for the safety of our patients and staff,” says Szabo.

Within three days, BIDMC's research enterprise had shifted gears, with many staff redeployed to new roles necessitated by the overwhelming crisis, including working with the Department of Pathology on the development of a COVID test. In addition, a number of research nurses stepped in to provide clinical assistance across the medical center.

It was like a hurricane struck, but we worked as a team to overcome every barrier we were faced with.
Gyongyi Szabo, MD, PhD
Chief Academic Officer
BIDMC and Beth Israel Lahey Health

Clinical Trials: What Is Driving This Virus?

Even as Szabo and her team were adjusting to the new demands imposed by laboratory closings, they recognized the urgent need to find treatments for COVID-19—and the critical role of clinical research. “Here was this brand new disease,” says Szabo. “We had to find out what was driving SARS-CoV-2, so we could better understand how to treat it.” So she convened a multidisciplinary group of pulmonologists, cardiologists, and infectious disease and emergency medicine specialists to evaluate and expedite BIDMC's participation in ongoing clinical trials. Together this team established new policies to maximize efficiency, centralize resources, triage an overwhelming number of requests, and optimize the experience of patients participating in COVID-19-related trials.

Nathan Shapiro, MD, was one of those specialists. As co-principal investigator of TREAT-NOW (Trial of Early Antiviral Therapies during Non-hospitalized Outpatient Window), Shapiro and his colleagues studied the early administration of the antiviral agent lopinavir/ritonavir. “In COVID-19, there is a week or so delay between the onset of symptoms such as fever and cough and the progression to pneumonia and respiratory failure,” says Shapiro, an emergency medicine physician. With an innovative telehealth approach, TREAT-NOW enables participants to have an initial consultation over the phone, receive medication to their homes via overnight mail, and be remotely monitored by phone calls and texts. “By intervening early, we can potentially keep COVID-19 from growing severe—and keep patients out of the hospital,” says Shapiro.

Infectious disease scientist Kathryn Stephenson, MD, MPH, led clinical studies at BIDMC testing the antiviral agent remdesivir for the treatment of early-stage COVID-19. One of her priorities was to ensure that her team enrolled patients from diverse racial and ethnic backgrounds in those studies. “As a scientist, I see incredible discoveries being made and yet, the people who need them the most often don't have access,” says Stephenson. “The country has a shameful history of conducting unethical experiments with patients of color, and we need to build trust in these communities. It's important for us to continue working toward diversifying our studies.” According to Stephenson, this is critical because certain populations may not respond as well to a therapy or vaccine, and healthcare institutions have a responsibility to ensure that potentially lifesaving treatments are offered equitably.

Ultimately, more than 100 clinical studies were conducted at BIDMC throughout the pandemic, including research demonstrating the virus's broader impact on health. A key investigation led by Rishi Wadhera, MD, and Robert Yeh, MD, MBA, for example, found that patients' reluctance to go to the hospital in the pandemic's early months may have led to an increase in deaths caused by ischemic heart disease and hypertensive disease, suggesting COVID-19 took an indirect toll on patients with heart disease.

A New Biobank: Preparing for What Lies Ahead

As cases of COVID-19 continued to grow, Szabo and her team realized that it was essential to collect and document biological data on this complex disease, to inform future studies. In the spring of 2020, they embarked on a major effort to gather specimens from patients hospitalized with COVID-19. “This initiative had to happen very quickly,” says Szabo. “With the help of funding from a generous donor, we were able to compile an organized collection of biological material that will be vital for future discovery.” The result was a comprehensive biobank, the first of its kind at BIDMC.

Ai-ris Collier, MD, a physician–scientist specializing in maternal–fetal medicine, together with pulmonologist Debby Ngo, MD, worked closely with nurses, doctors, and other frontline staff to acquire patient consent and collect a wide range of blood and other biological samples from patients being treated for COVID-19 at BIDMC. “We collaborated with scientists and clinical staff across BIDMC and other Boston-area institutions to pool invaluable data,” says Collier. “A biorepository of this scale that represents a diverse population will allow us to move science forward more quickly, particularly for understudied conditions like pregnancy, immunosuppression, and the long-term effects of COVID-19.”

“Our wealth of work in itself aims to directly help patients infected with this virus,” says Szabo, who has launched an ambitious five-year Institutional Strategic Plan for Innovation, Research & Education (InSPIRE) to reimagine the BILH research enterprise and prioritize harnessing the power of clinical data to improve patient outcomes. “It also echoes the broader vision of our research mission: to pursue investigations that will ultimately provide patients with the best possible care. The pandemic has demonstrated that we are even more effective, more powerful, when we collaborate across disciplines toward that mission.”

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