More Than $10M in Research Grants Awarded to Study Long COVID Impact on CVD Health

April 15, 2022 — Eleven teams of scientific researchers have been selected as recipients of American Heart Association research grants to study the long-term influence of COVID-19 on cardiovascular health. The “Mechanisms Underlying Cardiovascular Consequences Associated with COVID-19 and long COVID” grants total more than $10.6 million to support research team across the country over the next three years. The Association, the world’s leading voluntary organization focused on heart and brain health and research for all, is continuing to build the body of science related to the impact of COVID-19 as the worldwide pandemic moves into its third year.

“Research shows that 10% to 30% of people who have COVID-19 are experiencing lingering effects of the virus well beyond the initial 2-to-3 weeks expected recovery, a condition known as long COVID. Many of the short- and long-term complications of COVID-19 affect the heart and the brain and are contributing to an increase in cardiovascular disease in ways we do not fully understand,” said  American Heart Association President Donald M. Lloyd-Jones, M.D., Sc.M., FAHA, chair of the department of preventive medicine, the Eileen M. Foell Professor of Heart Research and professor of preventive medicine, medicine and pediatrics at Northwestern University’s Feinberg School of Medicine in Chicago. “It’s critical that we learn all we can about the pathways and mechanisms in which the virus that causes COVID-19 attacks the body, and, in turn, identify and develop new treatments to help reduce further risk and improve the health of people impacted by this disease. It’s very exciting to know that these new research grants will pave the way for groundbreaking and lifesaving discoveries.”

The 11 new research projects are underway as of April 1 and include:

• Role of SARS-CoV-2 ion channel ORF3a in COVID-19-associated thrombosis - Beth Israel Deaconess Medical Center in 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 in 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 in 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 heart beats 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 in 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 in 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 predicts 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 in 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 reduce 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, Fla.: 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 in 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 in 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, Tenn.: 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.

Lloyd-Jones noted that people with risk factors for cardiovascular disease, such as high blood pressure, diabetes and obesity, and those who have heart disease or survived a stroke may be more susceptible to severe COVID-19. They are particularly vulnerable to its effects, dying from the virus at rates of two to three times higher than people in the general population.

“COVID-19 has also disproportionately impacted people of color, including increased rates of hospitalization and death among American Indian or Alaska Natives, Black individuals and Hispanic or Latino people,” Lloyd-Jones said. “A number of these research projects will address those disparities and focus on inclusion of diverse populations.”

This latest research initiative extends the American Heart Association’s commitment to understanding and mitigating the biological effects of the infectious virus that causes COVID-19, as it is related to heart and brain. As the largest nongovernmental funder of cardiovascular and cerebrovascular research in the U.S., the Association recognized early in the pandemic the need to change course to meet developing needs precipitated by the emergence of COVID-19.

Since March 2020, the Association has:

• funded $2.4 million in research on COVID-19, the results of which are currently being reported;
• created a large, national registry of health records for patients hospitalized with COVID-19 - the Get With the Guidelines® COVID-19 CVD Registry;
• provided enhanced flexibility and up to $3 million in supplemental funding for recipients of AHA research grants;
• reviewed nearly 4,000 manuscripts focused on COVID-19 research in the Association’s 13 peer-reviewed scientific journals;
• disseminated more than 50 presentations on COVID-19 research at the Association’s premier scientific meetings; and
• established a collection of resources for health care systems, clinicians, patients and the public.

Overall, the American Heart Association has funded more than $4.9 billion in cardiovascular research since 1949.

For more information: www.heart.org