Mechanisms Underlying Cardiovascular Consequences Associated with COVID-19 and Long COVID

 

Role of SARS-CoV-2 ion channel ORF3a in COVID-19-associated thrombosis
Beth Israel Deaconess Medical Center, Boston
Led by Sol Schulman, M.D., Ph.D., an assistant professor of medicine, this team will learn more about how ORF3a, a part of the virus that causes COVID-19, leads to blood clotting in people with the infection. They will explore the use of a drug called benzbromarone, which is used in other countries to treat gout in humans, as a possible way to block the harmful effects of ORF3a and prevent the clotting process before it even starts.

Systems and Network Medicine Approach to Cardiovascular Complications of SARS-CoV-2 and Their Personalized Treatment
Brigham and Women's Hospital, Boston
Led by Joseph Loscalzo, M.D., Ph.D., chair of the department of medicine, this team will bring together experts from different fields with access to and expertise in a variety of new technologies, including computational biology, network science and systems biology, to study the specific mechanisms that cause cardiovascular complications in people with COVID-19. They plan to use the information to develop new treatments for the infection and its short- and long-term impacts.

Prolonged Electrophysiological Effects of the Cardiac Innate Immune Response to RNA Virus
Johns Hopkins University School of Medicine, Baltimore
Led by Brian O’Rourke, Ph.D., Robert L. Levy Professor in Cardiology and a professor of medicine, this team will study how the immune system and mitochondria (part of a cell that converts energy) cause variable heartbeats in people with COVID-19 that continue for a long time after the initial viral infection. Their goal is to determine how to prevent or reverse these aftereffects of COVID-19.

Role of TLR9 and Mitochondrial DNA in Regulating Microvascular and Immune Cell Dysfunction Post-COVID-19
Medical College of Wisconsin, Milwaukee
Led by Michael Widlansky, M.D., the Northwestern Mutual Professor of Cardiovascular Medicine, this team will look into why blood vessels continue to be unhealthy in people who have COVID-19 and they will explore whether the use of a dietary supplement called Lp299v can restore normal blood vessel function to improve the health of people after COVID-19 infection.

Rapid Cardiovascular MRI for Quantifying Coronary Microvascular Dysfunction in COVID-19 Survivors
Northwestern University, Chicago
Led by Daniel Kim, Ph.D., the Knight Family Professor of Cardiac Imaging and a professor of radiology, this team will study the mechanisms for how long COVID causes chest pain symptoms, determine if blockages of small heart blood vessels predict a person’s inability to exercise and explore the feasibility of an MRI is the ideal screening test for long COVID patients with chest pain symptoms.

SARS-CoV2 Infection and Type I Interferon Signaling in COVID-19 and Long COVID-Associated Endothelial Cell Dysfunction
Tulane University Health Sciences Center, New Orleans
Led by Xuebin Qin, Ph.D., a professor of microbiology and immunology, this team will study the role of the viral mRNA and protein found in pulmonary vascular endothelial cells during a COVID-19 infection. They’ll test whether antagonizing viral RNA expression or viral RNA signaling in these cells reduces COVID-19 severity and long COVID effects.

The Role of Viral Fragments in Long-Term Cardiovascular Sequelae of COVID-19
University of California, Los Angeles
Led by Jeffrey Hsu, M.D., Ph.D., a physician-scientist and instructor, in early research this team learned that even fragments of the SARS-CoV-2 virus that causes COVID-19, rather than the full virus itself, can impact healthy, uninfected cells. With this new funding, they will now explore how viral fragments may injure the heart and blood vessels and determine whether these viral fragments are detectable in people who have long COVID to learn more about how the infection impacts the heart.

Defective Cholesterol Homeostasis Causes Systemic Endothelial Dysfunction in Long COVID
Miller School of Medicine of the University of Miami
Led by Lina Shehadeh, Ph.D., a professor of medicine, this team will continue to explore their early findings that cholesterol storage inside the organs and cells of people with COVID-19, makes the infection worse. This can cause the immune cells to release toxic material that negatively affects the health of the blood vessels throughout the body. The team will look at ways to address this abnormal blood vessel condition that may cause the general long COVID symptoms.

Vascular Mechanisms Leading to Progression of Mild Cognitive Impairment to Dementia After COVID-19
University of Oklahoma, Health Sciences Center, Oklahoma City
Led by Andriy Yabluchanskiy, M.D., Ph.D., an assistant professor, this team found in early research that COVID-19 may accelerate memory loss and dementia in people with mild cognitive impairment. They will explore the mechanisms behind these findings by testing whether COVID-19 alters blood supply to brain regions and whether these changes contribute to the progression of memory loss in people with mild cognitive impairment.

Mechanisms Underlying COVID-19 Associated Vascular Thrombosis
University of Pennsylvania, Philadelphia
Led by Mark Kahn, M.D., the Edward S. Cooper, M.D./Norman Roosevelt and Elizabeth Meriwether McLure Professor of Medicine, this team, in earlier research, explored in vivo mechanisms of COVID-19 by generating new mouse models with conditional loss and gain of human angiotensin I converting enzyme 2 (ACE2), a key protein thought to be linked to the SARS-CoV-2 virus. They identified large clots in the blood vessels of the lung following virus infection in the nose and brain, findings that replicate human COVID-19 presentation. With this new funding, they’ll further explore and test these preliminary findings in mice to identify ways to more effectively prevent and treat thrombotic complications of COVID-19.

Cardiovascular Autonomic and Immune Mechanism of Post-COVID-19 Tachycardia Syndrome
Vanderbilt University Medical Center in Nashville
Led by Cyndya Shibao, M.D., an associate professor of medicine, this team hopes to discover a new treatment option for people who have COVID-19 and experience postural tachycardia syndrome (POTS), a disabling disease that causes extreme fatigue along with feelings of fainting and rapid heartbeats on standing. The planned treatment would involve delivering stimulation to the vagus nerves that control specific involuntary body functions such as digestion, heart rate and the immune system. This will hopefully reduce rapid heartbeats on standing and clear inflammation and other lingering COVID-19 symptoms.