The doctors on the front lines of the coronavirus pandemic may be aware of the health impacts that face survivors of mass shootings or natural disasters, but the highly contagious virus—one of the deadliest in history—is forcing them to grapple with a new question: if people who have beaten the disease should worry about their long-term health.
It is a question that’s front and center not just for doctors caring for patients, but also for researchers, many of whom are working frantically to understand the long-term effects of SARS-CoV-2—the virus that causes the coronavirus disease 2019 (COVID-19)—even as they try to develop effective therapies to beat it.
No small charge, but NHLBI is forging a way to help.
Enter the COVID-19 Observational Study, or the CORAL study, which will launch this month by NHLBI’s Prevention and Early Treatment of Acute Lung Injury (PETAL) Clinical Trials Network. The network is also behind a clinical trial to evaluate the safety and effectiveness of hydroxychloroquine to treat adults hospitalized with COVID-19.
For the CORAL study, researchers across approximately 50 participating PETAL network hospitals plan to enroll 3,000 adult patients admitted to a hospital who had, or currently have, a laboratory confirmed case of COVID-19. The hope is that researchers can use the data and samples of materials they collect on patients hospitalized with COVID-19 to be able to better characterize the disease, understand the underlying biology, predict health outcomes, describe the long-term outcomes, and come to a fuller understanding of the overall impact of the coronavirus on the health system.
“This study is critical to understand the epidemiology of hospitalized COVID-19 patients in the United States and their recovery,” said James P. Kiley, Ph.D., director of NHLBI’s Division of Lung Diseases. “CORAL is uniquely positioned to leverage the expertise of PETAL and is deliberately designed to work with global efforts to understand the clinical course, and outcomes of these patients.”
The current scientific literature documenting COVID-19 cases in the U.S. is scattered. But one large report from China, issued in late February, described roughly 44,000 people with confirmed cases of COVID-19. Although most had mild symptoms of the disease, nearly 20 percent were critically ill with lung injury that made breathing difficult. Among the critically ill, many experienced cardiomyopathy and catastrophic arrythmias, prompting a call for more research to study the outcomes and long-term health problems that many patients will face.
The CORAL study is taking charge by looking at two sets of patients: those who were admitted to a hospital and were since discharged, and those who are currently admitted. To learn about eligible participants already discharged from the hospital, researchers will access their electronic medical records for clinical data, chest radiographs, and CT scans. Data and chest imaging on patients currently admitted to the hospital will also be collected so that researchers can document how COVID-19 takes hold of air sacs in both lungs and fills them with fluid—a major hallmark of the disease and the culprit behind the inability to breathe.
To help better understand how COVID-19 impacts more than just the lungs, researchers will also collect information on patient’s cardiac function, and important laboratory tests for markers of inflammation, coagulation, injury to the heart, liver and kidneys, and immunity. Prior reports have documented that patients with poor outcomes, particularly the oldest and most severely ill, were more likely to have abnormal findings in these areas, as well as a higher risk of death.
“This study will help us better understand the different ways that COVID19 affects patients and what factors influence patient outcomes in both the short and long-term,” said Lora Reineck, M.D., M.S., program director of Acute Lung Injury/Critical Care Program in NHLBI’s Division of Lung Diseases.
For patients enrolled in CORAL, researchers will collect samples of blood, urine, as well as sputum and fluid from the lung.
“We hope that collecting and testing these samples will allow investigators to better characterize the illness by comparing the clinical characteristics with corresponding biological responses in acutely ill patients, ” said Neil Aggarwal, M.D., branch chief of the Lung Biology and Disease Branch in NHLBI’s Division of Lung Diseases. “That should give the research community and health care providers a better understanding of what biological factors predict severe illness and which patients may benefit from being treated early.”
Participants who survive hospitalization may additionally be contacted by phone up to six months after hospital discharge for a follow-up study. The assessment will measure the levels and rates of recovery, including a special focus on heart and lungs, in an effort to determine which risk factors are tied to poor outcomes.
Data collected in CORAL will be deposited into the World Health Organization’s International Severe Acute Respiratory and Emerging Infections Consortium registry, which aims to advance global efforts in understanding COVID-19. Researchers can expect early data sharing to accelerate their knowledge of the disease.
Kiley said the CORAL study effort came together out of urgency. “This is a rapidly evolving area where more data is critically needed,” he said. “This study plans to not only provide desperately needed insights to help patients and health care providers, but also serve as a resource for all researchers.”