COVID-19 Research at NYSCF

The new coronavirus (COVID-19) is an infectious respiratory disease that has resulted in a global pandemic. The disease results from infection with the SARS-CoV-2 virus and can cause symptoms such as fever, cough, extreme fatigue, and loss of smell or taste. In some patients, the infection leads to severe, life-threatening respiratory distress. As of March 2021, there have been more than 500,000 deaths due to COVID-19 in the United States alone.

Individuals with underlying conditions like respiratory issues, heart disease, and diabetes, seem especially vulnerable — but some individuals who are otherwise healthy develop severe cases, which may be a function of their genetics. In most cases, the immune cells in our body will recognize and clear the virus relatively easily, but in severe cases, an aggressive inflammatory response known as a ‘cytokine storm’ is triggered that ends up attacking the lungs and multiple organs. Scientists suspect that certain genetic mutations may make individuals more likely to trigger this life-threatening version of the immune response. NYSCF is part of the COVID-19 Genomics Research Network in New York City, a multi-institutional collaboration applying advanced genetic technologies and data analysis to understand the role of genetics in how individuals respond to SARS-CoV-2 infection. Any genetic mutations identified that are associated with more severe cases can readily be investigated and validated in our stem cell models (see below). This can help us on the road to predicting who is vulnerable to developing severe COVID-19, and to find better ways to treat them.

If we are to fully understand and properly treat this disease, we need laboratory disease models that show us exactly how the virus affects our bodies. The most commonly used disease models are: 1) traditional cell lines, which require manipulation to allow infection and do not reflect the immune response; 2) mouse models, whose equivalent virus ‘doorway’ does not let SARS-CoV-2 into their cells; and 3) ferret models, who show a very mild response to SARS-CoV-2 infection. Stem cells, on the other hand, can be easily generated from anyone’s blood or skin samples using NYSCF’s world-leading technology, and converted into the specific types of lung and immune cells involved in COVID-19. Stem cell models of COVID-19 also offer the advantage of being genetically identical to the person from whom they are made, giving us a basis to study what makes certain people vulnerable to severe cases of the disease. We can study how different individuals’ lungs respond to the virus in a laboratory dish, without disrupting the patients.

Scientific collaboration is happening at a pace we have never seen before. Collaboration has been core to NYSCF’s approach since day 1, as progress is slowed by silos, but accelerated when experts pool their resources and perspective. At NYSCF, we are making these stem cell models of COVID-19 available to the entire research community so that they can be used for a range of applications in understanding and treating the disease. We are already collaborating with several leading virologists and chemists across the globe who plan to use our COVID-19 models in their research, including:

• NYSCF–Robertson Investigator Alumna Shuibing Chen, PhD, of Weill Cornell Medicine. Dr. Chen is creating organoids (3D clusters of human tissue made from stem cells) that contain different types of cells believed to be most susceptible to SARS-CoV-2 infection. In a recent Cell Stem Cell paper, Dr. Chen evaluated the ability of 1,280 FDA-approved drugs to block SARS-CoV-2 entry into cells. In later stages of this research, she will use NYSCF’s automated technologies to scale up and accelerate her drug screens. Learn more about this work in Nature.
• NYSCF – Druckenmiller Fellow Alumnus Larry Luchsinger, PhD, of the New York Blood Center. Dr. Luchsinger is collecting samples from recovered COVID-19 patients and examining them for biomarkers (molecular signatures) that indicate an increased risk of severe reaction to the virus. Dr. Luchsinger will use NYSCF’s models to help validate his findings, and this work could lead to a test for predicting COVID-19 severity in different individuals.
• Sumit Chanda, PhD, Director of the Immunity and Pathogenesis Program, Sanford Burnham Prebys Medical Discovery Institute. Dr. Chanda recently performed a screen of 13,000 drugs that have already been approved for other diseases and could be repositioned for COVID-19. His screen yielded 50 potential drugs that he will use our models to validate, so that the most promising drugs can be advanced to clinical trials in patients.
• Nevan Krogan, PhD, Director of the Quantitative Biosciences Institute, University of California San Francisco, and Adolfo Garcia-Sastre, PhD, Director of the Global Health and Emerging Pathogens Institute of Icahn School of Medicine at Mount Sinai. Drs. Krogan and Garcia-Sastre published a study in Nature identifying 30 drugs that inhibit replication of the SARS-CoV-2 virus. These antiviral drugs are already clinical-stage or FDA-approved, and testing them in our stem cell models will allow us to prioritize the most promising candidates for clinical trials.

“This pandemic is devastating, but it has also brought about the most collaborative period of science that I’ve ever experienced,” noted MIT’s Feng Zhang, PhD, pioneer of CRISPR gene editing technology and NYSCF — Robertson Investigator Alumnus, during a recent webinar hosted by NYSCF. “I’ve probably met more people in the last four weeks than I typically would in a year, and everyone who I’ve reached out to about collaborating has been receptive. I think that speaks to how united we are in this fight.