Immunologists at the Icahn School of Medicine at Mount Sinai are playing a major role in managing the care of severely ill patients with COVID-19, who often experience an excessive inflammatory response to the disease that can ultimately overwhelm them.
Under the leadership of Miriam Merad, MD, PhD, the Mount Sinai Professor in Cancer Immunology and Director of the Precision Immunology Institute, Mount Sinai has created a quick test that monitors a patient’s inflammatory response to COVID-19 and helped launch a clinical trial that uses the drug sarilumab to manage these responses. The drug, manufactured by Regeneron Pharmaceuticals Inc., is typically used to treat rheumatoid arthritis. Dr. Merad says she may also roll out clinical trials that would test drugs used after CAR T cell adaptive therapies.
“Immunologists understand inflammation and know how to control it,” says Dr. Merad. “We developed a test with a three-hour turnaround time that we will repeat many times a day to see what type of inflammation the patient is developing and potentially guide treatment.” By identifying the features of severe immunological reactions in patients quickly, “we can speed the implementation of a cytokine blockade and significantly improve patient outcome.”
Cytokines are small proteins that modulate immunity. In trying to fight the COVID-19 virus the immune system may mount a major response, which can lead to excess inflammation that is also called a ‘cytokine storm.’ This overdrive reaction is happening in a range of COVID-19 patients, from the elderly to some young people with no apparent underlying health conditions.
“You need a strong immune response to fight the virus and this is why some people do well,” says Dr. Merad. “But others develop this storm of cytokines and this is what leads to fatalities. People are not dying from a virus that is running rampant in their bodies and killing tissue. We believe people are dying because of excessive inflammation. If we learn how to prevent this damaging immune response without compromising the fight against the virus we will be able to save many lives while waiting for curative treatment such as an antiviral drug or a vaccine.”
Dr. Merad adds, “There is urgency in learning how to best block the fatal inflammatory response.” To that end, she and other researchers are using the leading technology platform that she helped build in Mount Sinai’s Human Immune Monitoring Center, which allows them to “map with unprecedented depth the immune response to the virus in our patients.”
Benjamin K. Chen, MD, PhD, the Irene and Dr. Arthur M. Fishberg Professor of Medicine, and Vice Chair for Research in the Department of Medicine (Infectious Diseases), has been supporting the evolution of many proposed clinical trials with the help of leaders throughout the Mount Sinai Health System. Dr. Chen says there is limited but encouraging data to support cytokine blockers. Dr. Merad’s lab and the Human Immune Monitoring Center are uniquely capable of mapping out the “cytokine release profile,” he says. “With these trials we have the opportunity to measure those changes very carefully and decide what other trials or studies might be best to use for coronavirus. We are doing everything we can to support promising developments against COVID-19.”
Dr. Chen is working with Linda Rogers, MD, Associate Professor of Medicine (Pulmonary, Critical Care and Sleep Medicine), and Michele Cohen, Clinical Research Program Director in the Department of Medicine, who have been coordinating several major COVID-19 clinical trials at the Mount Sinai Health System. Judith A. Aberg, MD, the Dr. George Baehr Professor of Clinical Medicine and Chief of the Division of Infectious Diseases, Department of Medicine, is leading key clinical trials, including one for the antiviral drug remdesivir, made by Gilead Sciences. Remdesivir has shown promise in treating patients with COVID-19 and was developed in response to the Ebola crisis.
