Convalescent plasma therapy for COVID-19 patients -- an experimental approach of giving a transfusion of plasma collected from a donor who has recovered from COVID-19 to a patient with an active infection -- is the focus of a new two-part research initiative at Penn Medicine. Researchers will first collect plasma from people who have recovered from their infection under a donor research protocol. The second part involves conducting clinical trials to test the safety and efficacy of giving that plasma to moderately and severely ill hospitalized patients.
People who have recovered from COVID-19 rapidly develop antibody responses. Early reports suggest that these plasma antibodies can boost the immune response in severely-ill patients. By developing and implementing these research protocols in tandem, we will be able to use scientific and evidence-based methods to learn if, and how, convalescent plasma therapy helps patients. We're working to start our clinical trial as soon as we possibly can, because we urgently need to determine if this approach works and if it is safe."
Katharine Bar, MD, assistant professor of Infectious Diseases in Penn's Perelman School of Medicine
Bar will lead the clinical trial team at the Hospital of the University of Pennsylvania and Penn Presbyterian Medical Center. Nicole Aqui, MD, an associate professor of clinical Pathology and Laboratory Medicine, is leading the transfusion medicine team that began a research protocol to collect plasma from recovered COVID-19 patients this month.
"In addition to being home to the world's leading coronavirus basic science researchers with decades of experience, Penn has a longstanding expertise in apheresis collection. We are fortunate to have the opportunity to partner with infectious disease specialists to enable critically important clinical trials," Aqui said.
Researchers will begin enrolling patients into the clinical trial following approval from the U.S. Food and Drug Administration for an Investigational New Drug application. The first trial will include 50 patients and take up to four months to complete. Up to two units, or 500 milliliters, of plasma will be given to each patient enrolled in the trial.
"Because we will be using plasma collected at Penn in the clinical trials, we are going to know detailed information about the connection between the donor plasma and its effect on the patient recipient," said Don Siegel, MD, PhD, a professor of Pathology and Laboratory Medicine and director of Transfusion Medicine and Therapeutic Pathology. "We'll learn how to detect the presence and type of antibodies in a given plasma unit, how the patient did after receiving that particular unit, and hopefully be able to complete our understanding of the role passive immunity plays in treating our patients."
Physicians have been using convalescent plasma therapy to treat viruses for more than a century--including during the Spanish Flu epidemic. More recently, the therapy has been used to treat SARS-1, MERS and the H1N1 flu. Plasma is generally collected in two ways, through a major collection and distribution organization like the American Red Cross or in an academic medical setting like Penn.
"What takes Penn's investigative approach to the highest level is the integrated partnership between immunologists, microbiologists, transfusion medicine physicians, critical care physicians, infectious disease researchers and pulmonologists who are working side by side with great urgency and precision to more deeply understand the disease and the full impact of this and several other interventions," said Emma Meagher, MD, Vice Dean and Chief Clinical Research Officer in the Perelman School of Medicine and a professor of Medicine and Pharmacology.
"We have scientists with decades of experience at the bench collaborating with world-class clinicians providing care at the bedside - this is what Penn does best." said Andrew Fesnak, MD, an assistant professor of Pathology and Laboratory Medicine and a co-investigator on the donor protocol.
Two recent papers have shown positive results among critically-ill COVID-19 patients treated with convalescent plasma therapy. One study of ten severely-ill COVID-19 patients in Wuhan, China determined that one unit --200 milliliters--of convalescent plasma led to the improvement of clinical symptoms within three days and the disappearance of the virus from the blood in seven days. The study authors said results indicate the therapy is a promising rescue option for severely ill patients. Another study from China similarly showed clinical improvement among five critically-ill patients with COVID-19 and Acute Respiratory Distress Syndrome (ARDS). However, both were uncontrolled, observational studies describing small groups of participants.
Scott Hensley, PhD, an associate professor of Microbiology, has developed COVID-19 antibody assays to determine the level of antibodies in the convalescent plasma used to treat critically-ill patients and in the clinical trial. Hensley is also leading a project at Penn that will support testing for health care workers on the front lines using new COVID-19 serology tests, which determine infection and potential immunity to the virus. Researchers at Penn are also studying other treatment options, like hydroxychloroquine, working on vaccine development, and investigating the structure and behavior of the virus at the genomic level.