COVID-19 Research Projects

Moshe Levi, MD, Professor of Biochemistry and Molecular & Cellular Biology
Infection with SARS-CoV-2 can lead to severe acute respiratory syndrome, progressing to acute respiratory distress syndrome, cardiac abnormalities, gastrointestinal symptoms (including diarrhea) and kidney complications. These symptoms are associated with increased levels of substances known as cytokines (small proteins that can affect the immune system). Once the virus enters a cell, it induces cytokine release. The investigators hypothesize that SARS-CoV-2 induces dysfunction in the powerhouse of a cell (the mitochondria), leading to a chain reaction that results in the release of inflammatory cytokines and eventually multiorgan injury, dysfunction and destruction. In collaboration with international and local collaborators, laboratory studies will infect normal lung cells in culture that will then be analyzed for the presence of cytokines to try to identify new targets for therapy. Following the lab studies, the researchers will test viral infection and release of cytokines in young and old mice as models for increased severity of infection in older people.

Alex Kroemer, MD, Assistant Professor of Surgery
The MedStar Georgetown Transplant Institute (MGTI) serves people who have undergone organ transplants (e.g., liver, kidney, intestine, etc.) for whom COVID-19 might be especially devastating given their weakened immune systems and array of underlying conditions. The MGTI will leverage an existing immune-monitoring panel to study COVID-19 in patients compared to controls to determine treatment protocols for immunosuppressed COVID-19 patients. Specifically, the scientists will look at how distinct types of immune-fighting cells (e.g., NK cells and T cells) respond in MGTI patients with COVID-19. They will also look at the ratio of other immune-related cells, T-helper (Th) and regulatory T cells (Tregs), to see how that ratio affects lung function in COVID-19 patients. These studies will allow the scientists to correlate immunological data in their group of patients with clinical outcomes such as disease progression, complications, and/ or recovery.

Brent Harris, MD, PhD, Associate Professor of Neurology and Pathology
Coronaviruses in the past have been shown to be present in brain tissue. A large percentage of COVID-19 patients exhibit neurological signs and symptoms including fever, headaches, dizziness, as well as smell and taste abnormalities. For this proposal, the researchers will attempt to identify the presence of SARS-CoV-2 in specific regions of the central nervous system, possibly helping to inform how and where the infection happens in the brain as well as informing future treatment strategies. Harris is also the lead neuropathologist for the District of Columbia Office of the Chief Medical Examiner. He will work with this office and others medical examiners to obtain and sample specific regions of the brains of COVID-19-autopsied patients. If the test is positive for COVID-19, the researchers hope to localize where the virus cells lurk and investigate neuroinflammatory responses.

Newton Howard, PhD, Dept. of Biochemistry and Molecular & Cellular Biology
Current COVID-19 detection techniques utilize reverse transcription of RNA into DNA in the lab. This is a lengthy process, necessitating well-equipped laboratories and skilled personnel. The researchers propose combining three different technologies to rapidly derive a positive or negative result for the presence of anti-COVID-19 antibodies as well as active COVID-19 virus. Further, plans are for the scientists to take those results in hand and repurpose an optical detection tool they developed for brain implants and use it to detect coronavirus-specific proteins in those patients who test positive. A saliva specimen from the test-positive patients would be inserted on a chip into the optical detection handheld machine that would scan for COVID-19 specific proteins. The device will be portable enough to be used at home, at medical clinics, or other locations that require rapid testing. The machines could also be rapidly converted to connect to a desktop or smartphone so that the results could be read on those devices.

Al Fornace, MD, Professor of Oncology and Biochemistry and Molecular & Cellular Biology, and Heng-Hong Li, PhD, Assistant Professor of Oncology and Biochemistry and Molecular & Cellular Biology
Biomarkers found in blood and urine samples could be used to track the course of a COVID-19 -related illness and also predict its severity. The biomarkers should help clinicians distinguish between patients who are likely to show abruptly worsening symptoms from ones who are likely to recover. Dr. Fornace’s group has pioneered the use of molecular and genetic approaches to study a variety of disorders, including various types of pneumonia. Dr. Li’s lab has assessed changes in cellular metabolites and transcripts during responses to a variety of diseases in both patients and animal models. For their proposal, the researchers will meld their specialized techniques and knowledge to analyze blinded samples from COVID-19 patients with varying degrees of severity and differing clinical outcomes. Their hope is that the biomarkers they identify will tell them which patients may be at greatest risk and perhaps also help identify drugs that might work best against their biomarker targets.

Stephen Liu, MD, Associate Professor of Medicine
Researchers are constructing a comprehensive registry of COVID-19 infected patients treated at MedStar Georgetown University Hospital, which will include clinical history, hospital course and, importantly, a biorepository of blood samples to study COVID-19 infections and help develop effective treatment strategies. This biorepository will pool resources from multiple departments at Georgetown, including the departments of Infectious Disease, Pulmonary/Critical Care Medicine, Hematology/Blood Bank, Medical Oncology and Internal Medicine. A special focus will be the infection’s course among patients with cancer, including those receiving immunotherapy and chemotherapy, to understand how those treatments impact risk and outcomes. Blood will be collected, processed and stored for laboratory investigation and for banking to serve as an important future resource available to the Georgetown and MedStar research community.

Christopher Haas, MD, Assistant Professor of Medicine
Hydroxychloroquine (Plaquenil) is a drug that modulates the immune system and is used as an important therapy for people with autoimmune diseases including lupus as well as rheumatoid arthritis. The researchers propose an analysis of COVID-19-positive people based on two groups of patients in the Internal Medicine Clinics/Rheumatology Clinics within the Medstar hospital system. They will evaluate the incidence of COVID-19 infection in individuals with lupus or rheumatoid arthritis on hydroxychloroquine compared to those who have not taken the drug. With this analysis, the scientists hope to determine whether hydroxychloroquine has a COVID-19 protective effect. If so, the drug could be given to prevent new cases of COVID-19 and control the spread of infection.

Rebecca Katz, PhD, MPH, Professor of Microbiology & Immunology
To fill the urgent need for reliable data regarding COVID-19 infection, the researchers propose the development of a near real-time pandemic surveillance system fueled by a large-scale parsing of healthcare data. Such a system would fill the gap left by limited testing and tracking of cases and provide the ability to forecast hospital surge capacity. The investigators will access weekly, updated electronic healthcare reimbursement claims data from 100,000 healthcare providers across 45 billion healthcare transactions annually in the U.S., capturing data on infection by COVID-19 and its symptoms. Importantly, the data will include information on acute respiratory disease, fever, cough, shortness of breath, and other common COVID-19 symptoms. Using the data, the scientists will map out, model and predict the locations, timing and severity of COVID-19 in real time. They will share their findings with the National Governors Association, the U.S. Conference of Mayors and others so that they can make timely, well-informed decisions in the midst of the pandemic.

Catherine Broome, MD, associate professor of medicine (hematology/oncology)
Patients with either severe pneumonia, Acute Lung Injury (ALI) or Acute Respiratory Distress Syndrome (ARDS) associated with a confirmed COVID-19 infection (caused by a virus called Severe Acute Respiratory Syndrome-Coronavirus 2 or SARS-CoV-2), are eligible to participate in this research study to receive Ravulizumab (ULTOMIRIS®), a medication currently approved to treat complement-mediated diseases such as paroxysmal nocturnal hemoglobinuria in certain parts of the world. Complement-mediated diseases affect the immune system and its ability to fight bacteria or viruses and there is emerging scientific evidence supporting the role of complement in virally induced lung injury. The purpose of this study is to determine if ULTOMIRIS may reduce injury associated with severe pneumonia, ALI or ARDS associated with COVID-19 infection.

The research is being sponsored by Alexion Pharmaceuticals, Inc. Georgetown University is being paid by Alexion Pharmaceuticals, Inc., to conduct this study with Catherine M. Broome, MD, as the primary investigator. Broome is on the advisory board and occasionally serves as a paid consultant for Alexion Pharmaceuticals, Inc.

Michael Atkins, MD, Professor of Oncology and Medicine
During the course of the COVID-19 pandemic in the greater Washington, DC, area, hospital workers have a high risk of exposure. Cancer patients, particularly those on therapy, may have an increased risk of more severe disease should they contract the virus. The researchers propose to survey 1,000 hospital staff and 1,000 oncology patients during the last two weeks of April and collect basic demographic data and blood samples to serve as a baseline. In late June or early July another blood sample will be taken. These samples will be tested for immunity to SARS-CoV-2 using a soon to be determined antibody test. These test results will be linked to the survey results to identify the frequency and severity of viral exposure in these two populations and the factors that might influence these outcomes. This analysis will provide useful information regarding who can return safely to work and how best to protect cancer patients and staff during potential next waves of the pandemic.