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COVID-19 Research Grants Support Weill Cornell Medicine Investigators

an illustration of covid-19

Weill Cornell Medicine has awarded eight grants of $100,000 each to faculty for a variety of research projects on COVID-19, funded by the institution’s Board of Overseers and additional donors. The grants will support studies aimed at understanding fundamental aspects of the disease, the body’s immune response and social determinants of health that affect COVID-19 outcomes. 

Julie Magarian Blander, Ph.D. Gladys and Roland Harriman Professor of Immunology in Medicine

A T cell Biomarker for Protective COVID-19 Immunity

Identifying patients who have recovered from COVID-19 and are immune to future infection is essential to emerging from the pandemic. To do this, scientists must develop reliable tests for immunity to the SARS-CoV-2 virus. Though testing for antibodies to the virus is common, so far it is unclear whether they protect against future infection. Dr. Blander and her team will use blood collected from Weill Cornell Medicine and NewYork-Presbyterian/Weill Cornell Medical Center healthcare workers who recovered from COVID-19 to find virus-fighting immune cells called CD8 T cells. They will then identify the receptor these T cells use to find and destroy cells infected with the SARS-CoV-2 virus and try to develop a test to determine if individuals with this receptor are safe from future infections. If they are successful, it could lead to new tests that identify people who are protected from COVID-19 because they have recovered from SARS-CoV-2 infection or from a previous infection with a similar virus that generates a similar immune response.

Melissa Davis, Ph.D. Assistant Professor of Cell and Developmental Biology Research in Surgery (Interim)

COVID Disparities – DARC Side of SARS-Cov-2

Black patients have been disproportionately affected by COVID-19; they are more likely than the general population to develop severe symptoms and die from the illness. Dr. Davis will study how a common genetic mutation in people of sub-Saharan African ancestry, compounded by obesity, may contribute to worse COVID-19 outcomes among Black patients. The mutation, known as Fy and located in the ACKR1 gene, prevents the expression of a protein called Duffy Antigen Receptor for Chemokines (DARC) on the surface of red blood cells. Individuals with this mutation may be more susceptible to complications of COVID-19 caused by severe inflammation. That's because DARC helps reduce the accumulation of inflammatory factors and infiltration of white blood cells that can cause excess organ damage. That risk could be further exacerbated among Black patients by socioeconomic disparities that contribute to higher rates of obesity, which is a cause of chronic inflammation. Dr. Davis and her team will look at the relationship between inflammation and immune responses in lungs, blood and bone marrow and how these impact COVID-19 outcomes among patients of different races, ethnicities and body mass index. They will also create a mouse model to study how the DARC gene and obesity may modify the course of COVID-19. The studies may lead to improved treatments for COVID-19 and help efforts to reduce racial and ethnic disparities in illness.

Alexander Merkler, M.D. Assistant Professor of Neuroscience and of Neurology

Babak B. Navi, M.D., M.S. Associate Professor of Neuroscience and of Neurology

Incidence and Risk Factors of Stroke in Patients Hospitalized with COVID-19

Although COVID-19 primarily leads to respiratory symptoms, recent studies suggest that it may increase the risk of stroke and other neurological complications as well. However, past studies were performed at single institutions and were small. Dr. Merkler and his team will conduct a large, multicenter study to determine the incidence and risk factors for stroke among patients hospitalized with SARS-CoV-2 infection at centers participating in the American Heart Association’s population-based Cardiovascular Disease Registry. In addition, they aim to develop and validate a clinical risk stratification score and a computerized machine learning algorithm to help identify individuals at high risk for stroke among patients hospitalized with COVID-19. They plan to make these tools publicly available through the use of online calculators. 

Robert Peck, M.D., Ph.D. Associate Professor of Medicine and of Pediatrics

Chronic Kidney Complications of COVID–19 in a Cohort of HIV-infected and HIV-uninfected African Adults

Kidney problems are one of the most common symptoms of COVID-19, with half of infected patients showing some type of damage to the organ when they are seen by a doctor. What’s unclear is if these kidney problems will quickly heal, or if they will turn into long-term health issues. Dr. Peck and his team will study long-term kidney problems in people infected with the virus in their ongoing research of HIV-positive and HIV-negative adults in Tanzania. The issue is particularly important for people of African ancestry who are already more likely to have kidney problems. The research will build on the team's ongoing study of COVID-19 patients, funded by the National Institutes of Health, measuring kidney function with two standard medical tests. They will also use newer research tests that enable them to identify the site of the kidney injury. They plan to use these results to apply for a larger grant to study improved ways to prevent or treat heart and kidney problems caused by COVID-19. 

Erica Phillips, M.D., M.S. Associate Professor of Clinical Medicine

The Contributions of Socio-Behavioral Factors to Disparities in the COVID-19 Pandemic

COVID-19’s disproportionate impact on low-income neighborhoods, and Black and Latino populations, has been credited to higher rates of underlying illness in these communities. This study seeks to understand another contributor, socio-behavioral factors, which is critical to developing a vaccine program that protects the most vulnerable. The researchers will investigate how social determinants of health, particularly social cohesion and social capital, contribute to the uneven toll of COVID-19 across New York City.

They will randomly select adults who were evaluated for COVID-19 symptoms between March 1 and May 15 at NewYork-Presbyterian/Weill Cornell Medical Center, NewYork-Presbyterian Lower Manhattan, NewYork-Presbyterian Brooklyn Methodist Hospital and NewYork-Presbyterian Queens as participants. 

Examining data from the electronic medical record system, public data sources, and a survey they conduct, they will compare socio-behavioral, biological and environmental risk factors to determine the contribution of each to differences in hospitalizations between racial and ethnic groups.

Heidi Stuhlmann, Ph.D. Harvey Klein Professor of Biomedical Sciences, Professor of Cell and Developmental Biology and of Cell and Developmental Biology in Pediatrics

The Placenta as a Potential Site of SARS-CoV-2 Infection and Transmission 

The impact of SARS-CoV-2 infection during pregnancy on the health of mothers and their newborns is poorly understood and of significant concern. Pregnant women appear to have less severe symptoms after infection than the general population. However, basic questions about whether the virus infects the placenta and whether it can be transmitted to the fetus have yet to be answered. A recent study of SARS-CoV-2 positive mothers at NewYork-Presbyterian Hospital/Weill Cornell Medical Center provided evidence of abnormal development of blood vessels, called vascular malformations, in the placentas from some of these patients. Dr. Stuhlmann and her colleagues, Dr. Rebecca Baergen and Dr. Robert Schwartz, will examine the placenta to determine if it is a path for SARS-CoV-2 transmission from infected mothers to their babies. They will further investigate if the virus causes vascular abnormalities and lesions, including thrombosis.

Yawei Jenny Yang, M.D., Ph.D. Assistant Professor of Pathology and Laboratory Medicine

Understanding how COVID-19 Affects Pregnant Women and Newborns

Universal testing of pregnant women for COVID-19 is helping scientists identify symptomatic and asymptomatic infected mothers. Dr. Yang will study how common COVID-19 is among pregnant women and their babies, as well as how variants or mutations in the virus affect the severity of the illness. She will also investigate how a women’s immune response and placenta affect the clinical outcomes of both mother and baby. During pregnancy, the immune system does double duty, ramping up to protect the mother from illness, while also shielding the developing fetus from harm. Although the placenta supplies oxygen and nutrients and removes waste from the fetus, and plays a role in helping to shelter it as it is developing, it also provides a path for the infection to spread from mother to baby. In addition to helping clinicians better understand how COVID-19 affects pregnant women and their babies, Dr. Yang’s research may lead to new testing and treatment strategies for all patients.

Pengbo Zhou, Ph.D. Professor of Pathology and Laboratory Medicine

Small Molecule Inhibitor Rewires Cellular Protein to Augment its Anti-viral Activity against SARS-CoV-

Clinical trials show remdesivir, the anti-viral drug recently approved on an emergency basis by the U.S. Food and Drug Administration, appears to have statistically significant but limited effectiveness in treating severe COVID-19 patients, by blocking viral replication. In a search for a more effective therapy, Dr. Zhou and his team are investigating the effectiveness of a new anti-viral agent. In SARS-CoV-2, the viral nucleocapsid N protein, which is responsible for viral RNA replication and packaging, interacts with a host protein. Surprisingly, the host protein has two distinct and opposing functions in the coronavirus life cycle. It facilitates viral RNA replication, propagation and survival. At the same time, it antagonizes viral infection by inducing the host’s innate immune response. The investigators will test if a small molecule inhibitor called G3N2i can selectively block the pro-viral activity by expelling the viral nucleocapsid N protein from the host protein, preventing it from promoting RNA synthesis and propagating SARS-CoV-2. This will free up more host protein to fuel the anti-viral immune response, thereby turning this host protein into a fierce combatant against the coronavirus.

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