COVID-19 Research Projects
While the COVID-19 pandemic has presented the medical and scientific community with unrelenting and unparalleled challenges, the unique nature of the Severe Acute Respiratory Syndrome-CoronaVirus-2 (SARS-CoV-2), which causes COVID-19, provides for wide-ranging and potentially impactful areas of scientific exploration and understanding.
To that end, Georgetown University Medical Center researchers have launched more than a dozen laboratory studies in addition to clinical research covering a remarkable breadth and depth of critically important problems related to COVID-19. Click on each tab below to view the projects.
GUMC welcomes gifts to help fund this COVID-19 research.
Drug Discovery & Development
Determining if FDA-approved compounds influence SARS-CoV-2 entry
Gray Pearson, PhD, Associate Professor of Oncology
Tools that have been used to screen for genes that are required for a cancer to spread will be repurposed by the investigators to determine how 1,971 FDA-approved compounds influence SARS-CoV-2 entry into cells that line the lungs and trachea. The researchers hope to rapidly narrow their search to those compounds that could be deployed to block the entry of the coronavirus into vital cells.
Developing a test for screening of drugs that inhibit SARS-CoV-2 binding
Robert Speth, PhD, Adjunct Professor of Pharmacology & Physiology; Dr. Kathryn Sandberg, PhD, Professor of Medicine, Obstetrics & Gynecology, and Biochemistry and Molecular & Cellular Biology
Angiotensin-converting enzyme 2 (ACE2) is best known for its ability to lower blood pressure, protect the heart, and reduce inflammation. However, ACE2 is also the receptor for SARS-CoV-2, the virus causing COVID-19, as well as its cousin SARS (now known as SARS-CoV-1), which both use the ACE2 receptor to gain entry into the lung cells we use to breathe. This project is directed to finding available drugs that can be repurposed to use as inhibitors of the ability of the SARS-CoV viruses to infect cells.
Targeting of vulnerable RNA sequences in SARS-CoV-2
G. Ian Gallicano, PhD, Associate Professor of Biochemistry and Molecular & Cellular Biology
Viruses that affect breathing include the common cold, influenza, and COVID-19. With the exception of Tamiflu for the influenza virus, there are few drugs that can reduce the inflammatory ability of these viruses. By facilitating molecular targeting of vulnerable RNA sequences, the researchers have developed a novel drug approach that disables viral genes from generating viral protein particles. A particular type of RNA (microRNAs, which are snippets of non-coding RNA) has been generated to specifically target vulnerable viral RNA sequences that act as a master switch for SARS-CoV-2 replication, infection, and stimulation of inflammation. This microRNA-targeted approach has been recently funded by the American Heart Association for testing models of human heart failure with clear evidence of returning cardiac function to normal parameters. The approach has also seen very recent success in patients with Huntington’s disease. As a demonstration of team science, the virology aspect of this project will also be guided by John Casey, Department of Microbiology, Georgetown University.
Repurposing drugs as SARS-CoV-2 inhibitors
Siva Dakshanamurthy, PhD, Professor of Oncology
Sometimes repurposing, or finding new uses for old drugs, can be advantageous. AZT was developed as a cancer drug but was not found to be effective. Years later, it was repurposed as one of the first effective drugs against the AIDS virus. A recent screening by the investigators showed hydroxychloroquine (a drug used experimentally to treat COVID-19 via the FDA’s Emergency Use Authorization), has potential but whether or how it might work is still unknown. The researchers propose utilizing their proven high-powered artificial intelligence computing technology to structurally model the interaction of COVID-19 with every known FDA-approved drug (and new small compounds) to determine if any of them can treat the COVID-19 viral infection. Future stages of investigation would involve studying drug candidates in animal models and then in human clinical trials.
Using lung cells infected with SARS-CoV-2 for drug screening
Xuefeng Liu, MD, Professor of Pathology and Oncology
The researchers have developed a new technique using lab cultures of lung and other airway cells that mimic what would occur in a living organism. They will functionally immortalize, or keep lung, trachea and nasal cavity cells proliferating indefinitely, so they can be tested to determine how SARS-CoV-2 enters and damages human target cells directly and indirectly. They will also try to determine if any particular drug from a unique collection of 348 antiviral compounds is able to block viral entry, induce a hyper-response that worsens inflammation and disease, or enables replication into target cells.
Discovering potential anti-COVID-19 compounds in repurposed drugs
R. Pad Padmanabhan, PhD, Professor of Microbiology & Immunology
The researchers are using novel tests to identify repurposed drugs that might target viral replication and infection. The investigators have three goals: develop a model to test FDA-approved antimalarial drugs for activity against COVID-19; test the efficacy and viral cell-killing ability of the drugs; and test the efficacy of combinations of antimalarial compounds with a protease inhibitor (such inhibitors have shown benefit in combinations with other drugs against the AIDS virus).
Mechanisms & Pathogenesis
Identifying targets against SARS-CoV-2 respiratory syndromes
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.
Studying transplant patients with COVID-19
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.
Studying brain tissue infected with SARS-CoV-2
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.
Novel Diagnostics, Integrated Databases & Biomarkers
Developing a rapid, portable detection kit for COVID-19
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.
Searching for biomarkers of disease severity in COVID-19 patients
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.
Building a COVID-19 biorepository
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.
Determining if hydroxychloroquine is effective against COVID-19
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.
Developing a real-time surveillance system for COVID-19
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.
A Phase 3 Open-label, Randomized, Controlled Study to Evaluate the Efficacy and Safety of Intravenously Administered Ravulizumab Compared with Best Supportive Care in Patients with COVID-19 Severe Pneumonia, Acute Lung Injury, or Acute Respiratory Distress Syndrome
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.
Analyzing COVID-19 Infection at a Medical Center
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.