NUCATS Presents Trio of COVID-19 Collaborative Innovation Awards
Each new research project was initiated at the Northwestern University Clinical and Translational Sciences (NUCATS) Institute’s COVID-19 Symposium. The awards are supported by NUCATS and philanthropic donations to Northwestern University Feinberg School of Medicine. Co-sponsors include the National Institutes of Health’s National Center of Advancing Translational Sciences, the Bluhm Cardiovascular Institute Clinical Trials Unit, the Emerging & Re-Emerging Pathogens Program (EREPP) in the Division of Infectious Diseases, the Feinberg School of Medicine Office of Research and the Institute for Public Health and Medicine (IPHAM).
“We are really excited about this project, not only because it will investigate key aspects of COVID-19 disease, but also for the fantastic opportunity to start a collaboration between the Division of Infectious Diseases Pathogen Genomics team and the Successful Clinical Response in Pneumonia Therapy (SCRIPT) team,” says Lorenzo-Redondo, research assistant professor of Medicine in the Division of Infectious Diseases. “I am confident that this collaboration will be extremely successful, and the studies proposed will advance significantly our understanding on how to better predict and prevent severe COVID-19 outcomes.”
Lorenzo-Redondo is joined by Sasha Misharin, MD, PhD; Judd Hultquist, PhD; Egon Ozer, MD, PhD, and Lacy Simons on a project that will examine if changes in SARS-CoV2 — the virus that causes COVID-19 —occurring inside a patient’s body during the infection can influence the severity of the disease itself.
It is estimated that approximately 80 percent of COVID-infected individuals are asymptomatic or experience only mild illness, however, 20 percent become severely ill and require hospitalization. A substantial proportion of hospitalized patients progress to respiratory failure requiring mechanical ventilation, and 40 percent of these individuals will have poor outcomes such as death or intubation for longer than two weeks.
“Although, multiple studies have already identified several clinical and demographic factors that increase the likelihood of hospitalization for COVID-19, including age, hypertension, diabetes, and obesity, the risk factors for poor outcomes once hospitalization has occurred are less clear,” says Lorenzo-Redondo. “We hypothesize that genetic characteristics of SARS-CoV2 and the way the virus changes in some people during infection can influence the outcome of hospitalized patients, and we hope to provide critical information that will improve patient care and help better understand COVID-19 outcomes.”
COVID-19 and Kidney Research
Pinelopi Kapitsinou, associate professor of Medicine in the Division of Nephrology and Hypertension, will work with collaborators Anand Srivastava, MD, MPH; Scott Budinger, MD; and Richard Wunderink, MD, to learn more about the cross-talk between the kidney and lung in severe COVID-19 pneumonia.
The multidisciplinary research project will combine the expertise in acute kidney injury epidemiology and pathophysiology (Srivastava and Kapitsinou) with systems biology knowledge and resources (Budinger and Wunderink).
“We are thrilled to pursue this project through the COVID-19 Collaborative Innovation Award,” says Kapitsinou. “Although the COVID-19 pandemic has not altered my research focus, it has emphasized the need for translational research. In this context, I started to wonder how similar or different the acute kidney injury is in the setting of COVID-19 compared with other types of critical illness.”
It is estimated that as many as one in three patients in the hospital with COVID-19 and especially those in the ICU are at risk for acute kidney injury. Severe acute kidney injury is associated with mortality rates near 50 percent.
Batlle, the Earle, del Greco, Levin Professor of Medicine, previously published on the underreporting of acute kidney failure in COVID-19 patients and the development of novel soluble ACE2 proteins for the potential treatment of COVID-19 and kidney disease. His Collaborative Innovation Award will fund the pursuit of a way to block the main entry point of SARS-CoV2 into humans.
Batlle, the Earle, del Greco, Levin Professor of Medicine, previously published on the underreporting of acute kidney failure in COVID-19 patients. His Collaborative Innovation Award will fund the pursuit of a way to block the main entry point of SARS-CoV2 into humans.
“We are excited about this award as it recognizes our effort to pursue the identification of a plasma factor that inhibits binding of SARS-CoV-2 to its host receptor, Angiotensin Converting Enzyme 2 (ACE2),” says Batlle.
Initial findings were made by Jan Wysocki, MD, PhD, as part of the Batlle lab’s focus on soluble ACE2 proteins for the treatment of COVID-19. The Batlle lab has found that plasma — the portion of blood that remains after red blood cells, white blood cells, platelets, and other cellular components are removed — harvested from donors who do not have antibodies for SARS-CoV-2 (COVID-19 negative) inhibits the binding of the virus to ACE2.
Batlle’s collaborators include Jan Wysocki, MD, PhD; Jack Henkin, PhD; Neil Kelleher, PhD; Pablo Penaloza-MacMaster, PhD; Michael Ison, MD, MS; and Luise Hassler.
The experiments in Batlles lab are geared to determine the characteristics of the inhibitor. Wysocki and Henkin will design a set of studies performed by Hassler. Ison has facilitated access to plasma samples from one of his studies that involves COVID-19 negative patients. Kelleher, director of Northwestern Proteomics, will ultimately carry out the proteomic identification of the plasma factor while the Penaloza-MacMaster lab will perform studies to evaluate neutralization of virus by the factor.
Each COVID-19 Collaborative Innovation Award team recognizes the role of NUCATS, symposia co-sponsors, and philanthropic gifts that allowed for their research to take place.
“The COVID-19 symposia were critical to the development of this proposal. It was only after Dr. Wunderink’s presentation that we realized the exceptional opportunity we had to understand the association between viral characteristics and COVID-19 severity,” says Lorenzo-Redondo. “Through his presentation we learned about the priceless longitudinal bronchoalveolar samples SCRIPT has collected from intubated COVID-19 patients. This sample set constitutes a unique resource to study the virus in critically ill patients. After the symposia our Infectious Diseases team contacted the SCRIPT team and we worked together to generate this clinically relevant proposal.”
The NUCATS Institute is supported, in part, by the National Institutes of Health's National Center for Advancing Translational Sciences, Grant Number UL1TR001422. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Written by Roger Anderson