Mount Sinai Developing an “End-to-End” Diagnostics Solution for COVID-19 That Incorporates Diagnosis, Treatment Selection, and Monitoring of Disease Course
An expert team of researchers and clinicians in microbiology, virology, pathology, molecular science, and immunology at the Icahn School of Medicine at Mount Sinai (ISMMS) and The Mount Sinai Hospital (MSH) have been working together around the clock to design, validate, and implement an “end-to-end” clinical pathology laboratory solution that will allow for the testing of approximately several hundred people per day in order to rapidly diagnose and help guide the selection of treatment and monitor disease course.
Using a high-throughput, automated molecular assay, The Mount Sinai Hospital Clinical Laboratories are currently testing several hundred patients per day for SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19) to identify positive versus negative cases. The testing effort will ramp up to a capacity of 1,000 tests per day. Mount Sinai follows NY State guidelines and is only testing patients with trouble breathing and/or moderate-to-severe respiratory symptoms at this time. (Please consult your physician if you believe you are a candidate for testing.)
For patients who test positive for SARS-CoV-2, a quantitative assay designed and implemented by a multidisciplinary Mount Sinai team is capable of measuring whether the patient’s viral load is high or low. The viral load findings will be studied to ascertain whether they assist in managing the disease and aiding in the selection of effective treatments. The clinical laboratory efforts are being led by Peter Palese, MD, Horace W. Goldsmith Professor and Chair of Microbiology, and Carlos Cordon-Cardo, MD, PhD, Irene Heinz Given and John LaPorte Given Professor and Chair of Pathology, Molecular and Cell-Based Medicine.
Internationally renowned researchers and clinicians from ISMMS and MSH are also tackling some other important tests to help in the fight against COVID-19, including:
A Blood Test That Measures Immunity in Recovered COVID-19 Patients
To help uncover just how widespread the novel coronavirus is within communities, a team led by virologist Florian Krammer, PhD, Professor of Microbiology at the Icahn School of Medicine at Mount Sinai, developed a serological enzyme-linked immunosorbent assay (ELISA) test. This test measures the presence or absence of antibodies to the virus in people’s blood. Similar to the most commonly used tests for other viruses, such as hepatitis B, this test shows whether a person’s immune system has ever come into contact with the virus (even months ago). There are three main advantages to this test: providing an accurate picture of how many people have been infected; identifying people with new immunity to SARS-CoV-2 who could care for COVID-19 patients at zero or minimal risk; and identifying newly recovered patients with high antibody levels who can donate their antibody-rich blood, known as convalescent plasma, to potentially save other patients with severe COVID-19. Initially the testing will be limited to potential plasma donors until testing capacity increases.
The team began working on this serological assay in January, before COVID-19 had been seen in the United States. To make this test, the researchers cloned animal cells to produce copies of the telltale “spike” protein that is present on the surface of SARS-CoV-2. That protein is highly immunogenic, meaning that people’s bodies see it and start making antibodies that can lock onto it. The test involves exposing a sample of blood to bits of the spike protein. If the test “lights up,” it means that person has the antibodies. Viviana Simon, MD, PhD, Professor of Microbiology at ISMMS, was instrumental in the design and implementation of the test, which has been approved for clinical use by the New York State Wadsworth Laboratory and is currently undergoing validation and urgent implementation. ISMMS medical students are establishing a social media campaign to identify volunteers to be tested.
“Our test can pick up the body’s response to infection as early as three days post-symptom onset and it could help locate survivors who are ‘hyper-immune,’” says Dr. Krammer. “Those people could then potentially donate their convalescent plasma to help very sick COVID-19 patients in intensive care units to help boost their immunity.”
The sensitive and specific identification of SARS-CoV-2 that ELISA provides will also support screening of health care workers to identify those who have already been exposed and are already immune. Those staff could then be deployed to the front lines to perform the riskiest tasks—like intubating a person infected with the virus—without worrying about getting infected or spreading the disease to colleagues, other patients, or their families. To learn the true extent of infections, the next step will be for researchers to carry out these serological surveys via blood draws from large numbers of people in an outbreak area, which may tell them exactly how many cases have gone unnoticed.
According to Dr. Krammer, efforts by the team at Mount Sinai and a few others developing similar tests (including the U.S. Centers for Disease Control and Prevention) to carry out a wider survey are just getting started, so it will likely be some time before scientists learn just how widespread SARS-CoV-2 is. The Mount Sinai Hospital Clinical Laboratories are also sharing specimens from recovered patients with the New York State Wadsworth Laboratory to assist other facilities in this effort.
A Test That Can Determine When a COVID-19 Patient Is Entering a Dangerous Point in Their Disease and a Drug Trial for a Subset of Those Patients
Mount Sinai’s Human Immune Monitoring Center, led by Miriam Merad, MD, PhD, Mount Sinai Endowed Professor in Cancer Immunology and Sacha Gnajtic, PhD Associate Professor of Immunology and Hematology/Oncology, are working on a test called the Ella ™ Cytokine Storm Panel to determine when someone infected with COVID-19 is entering a critical point in their disease. When patients take a turn for the worse, they are experiencing a burst in their body’s immune response, particularly with a group of immune molecules called cytokines. This burst of cytokines, called cytokine release syndrome or a “cytokine storm,” contributes to the severity of COVID-19, because the cytokines attack the patient’s organs, which can be fatal in some cases.
Mount Sinai clinical laboratories will use the Ella ™ Cytokine Storm Panel in COVID-19 patients who have been admitted to the hospital to monitor them and know, in real time, when they are experiencing cytokine storm. The test results are available in a few hours, and can be repeated throughout the course of care to help guide hospital care and to measure the response to experimental drugs given in clinical trials for COVID-19 patients.
Coupled with the Cytokine Storm Panel, Mount Sinai’s Division of Infectious Diseases, led by Judith A. Aberg, MD, will begin several clinical trials for patients with COVID-19. Their team has analyzed data from China showing that the cytokine release syndrome is killing COVID-19 patients and that inhibiting the storm using therapies tested in cancer patients who received CAR-T cells—modified immune system cells used to fight cancer—may improve their condition. Mount Sinai’s Human Immune Monitoring Center will be monitoring patients on all experimental trials to identify biomarkers response and guide additional therapeutic strategies.
“Some of the best researchers in the world, giants on the frontier of the fields of infectious disease, microbiology, emerging pathogens, and immunology, are here at the Icahn School of Medicine at Mount Sinai and The Mount Sinai Hospital. Since the COVID-19 pandemic began, they have been tracking the data coming out of China and Italy to mount a response that will help diagnose and treat ill patients,” says Dennis S. Charney, MD, Anne and Joel Ehrenkranz Dean, Icahn School of Medicine at Mount Sinai, and President for Academic Affairs, Mount Sinai Health System. “Our health system has fast-tracked funding and approvals for these tests and clinical trials to help patients not just within our own community, but to help people around the globe.”
To support COVID-19 research and response efforts, visit https://www.mountsinai.org/covid19research.
About the Mount Sinai Health System
The Mount Sinai Health System is New York City's largest academic medical system, encompassing eight hospitals, a leading medical school, and a vast network of ambulatory practices throughout the greater New York region. Mount Sinai is a national and international source of unrivaled education, translational research and discovery, and collaborative clinical leadership ensuring that we deliver the highest quality care—from prevention to treatment of the most serious and complex human diseases. The Health System includes more than 7,200 physicians and features a robust and continually expanding network of multispecialty services, including more than 400 ambulatory practice locations throughout the five boroughs of New York City, Westchester, and Long Island. The Mount Sinai Hospital is ranked No. 14 on U.S. News & World Report's "Honor Roll" of the Top 20 Best Hospitals in the country and the Icahn School of Medicine as one of the Top 20 Best Medical Schools in country. Mount Sinai Health System hospitals are consistently ranked regionally by specialty and our physicians in the top 1% of all physicians nationally by U.S. News & World Report.