July 15, 2020—(BRONX, NY)—As the number of COVID-19 cases continues to rise in the United States and around the world, researchers at Albert Einstein College of Medicine and Montefiore Health System are conducting a range of studies to learn more about the novel coronavirus and blunt the impact of the disease. Now, four Einstein and Montefiore research teams have received pilot funding from Einstein’s Office of the Dean to advance their projects targeting COVID-19. From discovering antiviral compounds and developing monoclonal antibodies, to using artificial intelligence to make clinical decisions and understanding how age affects the immune response, these investigators are helping to tackle this deadly pandemic.
“For the past few months, Einstein and Montefiore have been on the frontlines of the COVID-19 crisis, both on the hospital wards and in the laboratory,” said Gordon F. Tomaselli, M.D., the Marilyn and Stanley M. Katz Dean at Einstein. “As a result, our community knows better than most the desperate need to act quickly and decisively to challenge this viral threat.”
The Office of Development and Alumni Relations spearheaded the effort to quickly raise philanthropic funds to sponsor COVID-19 research at Einstein. Initiated with a $1 million challenge grant from Michael F. Price and the Price Family Foundation, dozens of major donors and foundations old and new to Einstein, including several members of the Board of Trustees and the Einstein Women’s Division, have contributed to ensure $2 million was swiftly amassed and the funds distributed.
“Given our history with this disease and our institutional strengths, Einstein and Montefiore are primed to spearhead the fight against COVID-19,” explained Dr. Tomaselli. “By quickly engaging our deep bench of basic science, translational, and clinical investigators, they were able to launch a swift response—pooling their extensive knowledge, experience, and resources in immunology, virology, drug design and development, medical care, and more to advance against this pandemic.”
The four initial $50,000 pilot projects receiving funding are:
Therapeutics Development: Development of Small Molecule Inhibitors
Principal Investigator: Evripidis Gavathiotis, Ph.D.
Co-Investigators: Bogos Agianian, Ph.D., Adolfo Garcia-Sastre, Ph.D., Kris White, Ph.D. (at Icahn School of Medicine at Mount Sinai)
Effective antiviral drugs are needed against SARS-CoV-2, the virus that causes COVID-19. Dr. Gavathiotis and his colleagues seek to identify existing Food and Drug Administration-approved antiviral drugs or develop new ones that can be rapidly used in clinical trials. The researchers plan to target the SARS-CoV-2 main protease (an enzyme that breaks down proteins), known as Mpro. This enzyme plays an essential role in the virus’ replication and transcription, making it an important drug target.
Using their expertise in chemical and structural biology, medicinal chemistry, and drug discovery, the investigators will first screen a library of approximately 2,300 FDA-approved and experimental drugs for those that can bind to and inhibit Mpro. Based on the hits from this screen, they then plan to design and optimize SARS-CoV-2 Mpro inhibitors and test their ability to inhibit SARS-COV-2 in viral replication and infectivity assays.
Lessons from Children: Differentiating the Immune Response To COVID-19 By Age and Outcome
Principal Investigator: Betsy Herold, M.D.; Co-Investigator: Marla Keller, M.D.
Studies show that most children have relatively mild COVID-19 that rarely progresses to acute respiratory disease syndrome (ARDS). This offers the opportunity to identify the quantitative and qualitative differences in immune response to COVID-19 in children and adults that may contribute to different outcomes, and identify which aspects of the immune response are protective and those that drive disease progression.
Using bio-specimens obtained from the large number of pediatric and adult cases at Montefiore, Drs. Herold and Keller plan to identify anti-COVID antibodies and assess their function (neutralizing, non-neutralizing vs. enhancing) at different times over the course of infection, to learn whether immune responses differ by age and outcome. To analyze how cells respond to coronavirus infection, they will measure their cytokines, the pro-inflammatory proteins that trigger ARDS. They will also explore differences that influence whether inflammation progresses to ARDS or to the recently described Pediatric Multisystem Inflammatory Syndrome.
Human and Bispecific Antibodies Against SARS-CoV-2
Principal Investigators: Jonathan R. Lai, Ph.D., and Kartik Chandran, Ph.D.
The novel coronavirus SARS-CoV2 recognizes and infects cells using its viral surface spike protein (S). Studies using convalescent plasma to treat COVID-19, suggest that serum antibodies help against active infections.
Drs. Lai and Chandran will identify and characterize human monoclonal antibodies (mAbs) from patients who have recovered COVID-19 that target the S protein. They will also use those mAbs as templates for design of bispecific antibodies— artificial antibodies that can bind to two different sites, or epitopes, on a virus or other microbe. By targeting multiple epitopes simultaneously, bispecific antibodies will reduce the risk that SARS-CoV2 will escape the body’s immune response. After developing the most reactive of those antibodies into monoclonal antibodies, they will combine the monoclonal antibodies with the most favorable characteristics into bispecific antibodies.
AI Radiology to Improve Delivery of Care for COVID-19 Patients
Principal Investigator: Michael L. Lipton, M.D., Ph.D.
Co-Investigators: Jeffrey Levsky, M.D., Ph.D., Parsa Mirhaji, M.D., Ph.D., Tim Duong, Ph.D. (at Stony Brook University)
The portable chest X-ray (CXR) has become indispensable for managing COVID-19 lung infection. It is well suited for imaging patients with active infections, revealing the classic COVID-19 pathology of bilateral, peripheral hazy lung opacities.
Dr. Lipton and his co-investigators aim to develop an artificial intelligence (AI) algorithm for evaluating CXR images, along with extensive patient data, for use in various situations. At admission, for example, the AI approach can help diagnose and triage patients according to disease severity: whether the patient requires hospital admission, intensive care, or mechanical ventilation, and the probability that a patient will live. Ultimately, the researchers aim to develop an algorithm that can accurately assess treatment response and predict disease progression. Such an algorithm could lead to much more efficient resource allocation and enhance patient care in medical centers coping with the COVID-19 pandemic.
In addition to the pilot awards, the philanthropic funds will provide support for the use of shared facilities with a number of microgrants to several laboratories.