Benhur Lee, MD, Professor of Microbiology and Ward-Coleman Chair in Microbiology

As governments make plans to reopen their economies and seek reliable ways to ensure their populations can get back to work safely, high-quality antibody testing has emerged as the only way to truly determine which individuals may be protected against the SARS-CoV-2 virus that causes COVID-19. Microbiologists at the Icahn School of Medicine at Mount Sinai have created tests that are answering that need.

A team of scientists led by Benhur Lee, MD, Professor of Microbiology and Ward-Coleman Chair in Microbiology, has developed an assay that tests the quality of an individual’s antibodies to see whether they strongly neutralize the SARS-CoV-2 virus.

Using technology that differs from the more commonly used ELISA method of testing for antibodies, Dr. Lee’s lab has built an identical replica of the outer portion of the SARS-CoV-2 virus, or a pseudo virus. This replica allows researchers to see how well the antibodies from recovered patients actually block SARS-CoV-2 from entering into cells and effectively stop the infection in its tracks. Such neutralizing action provides confirmation that an individual is protected against the virus.

Using the ELISA test and the pseudo virus test together shows how well antibodies that bind to the spike protein also correlate with virus neutralization, says Dr. Lee. The two-step process can provide governments and institutions with a critically important starting point in effectively determining which individuals have been exposed to the virus and carry neutralizing protection.

There are still many unknowns. While the scientific community at large agrees that immunity to the SARS-CoV-2 virus offers protection from re-infection, there is no firm understanding of how long that immunity will last. In addition, researchers do not know whether there is a threshold or level at which antibodies correlate with immunity.

“The gold standard in determining whether someone carries neutralizing antibodies is by using a live virus to test their serum after it has been drawn,” says Dr. Lee. “But this is not scalable for the hundreds of thousands of samples that will need to be tested. So what we developed is a safe surrogate that represents the real virus and can be automated with high-throughput testing in scientific facilities used by many governments and universities around the world.”

Dr. Lee says his pseudo virus assay is essentially a bridge between the binding capability of the ELISA test and the “gold standard” of live-virus neutralization, which requires laboratories to carry a higher, biosafety-level-3 (BSL 3) designation, allowing them to work with dangerous or potentially lethal agents. The pseudo virus can be handled in more commonplace biosafety-level-2 (BSL 2) laboratories that are designated for working with milder agents.

The new pseudo virus can serve as a platform for creating and optimizing potential vaccine designs, generating monoclonal antibodies, and screening anti-viral peptides—all of which would be used to treat or prevent COVID-19.

Government health agencies and universities in the United States and around the world have been sending formal requests to use Dr. Lee’s assay, and he says he will look to them for feedback on how well it is working. “We’re spending time investing in quality control,” he says. “It is important that when we send out this test it works the way we say it works.”

A renowned team of virologists, pathologists, and clinicians at the Mount Sinai Health System developed, validated, and launched a blood test for COVID-19 antibodies that received the U.S. Food and Drug Administration’s (FDA) emergency use authorization late Wednesday.

The blood test determines whether individuals have antibodies to the SARS-CoV-2 virus that causes COVID-19. It is used for the qualitative detection of human IgG antibodies in serum and plasma that is collected from individuals suspected of having been infected with SARS-CoV-2.

Early development of the assay, led by Florian Krammer, PhD, Professor of Microbiology at the Icahn School of Medicine at Mount Sinai, enabled Mount Sinai to become the first health system in the nation to undertake a convalescent plasma program that transfers the antibody-rich plasma from recovered COVID-19 patients into those who are critically ill.

To date, Mount Sinai has identified more than 1,900 donors who are eligible to provide their antibodies. A total of 141 patients have received the protocol, and the results are being evaluated clinically.

Under the leadership of Peter Palese, PhD, Horace W. Goldsmith Professor and Chair of the Department of Microbiology, Mount Sinai has built one of the world’s leading academic institutions for the study of viruses and emerging pathogens. “The COVID-19 antibody test is not only helpful in identifying individuals who could be donors for the convalescent plasma program but also identifies persons who can safely go back to work now that they are immune to the virus,” Dr. Palese says. This important step would allow the nation to return to economic productivity.

“We are grateful to the FDA for granting this expanded authorization so that we can deploy this vital test to the community at large,” says Carlos Cordon-Cardo, MD, PhD, Irene Heinz Given and John LaPorte Given Professor and Chair of Pathology, Molecular and Cell-Based Medicine. Dr. Cordon-Cardo oversaw the validation of the test that is produced by the Mount Sinai Laboratory, Center for Clinical Laboratories. The Mount Sinai Hospital’s Clinical Laboratories are certified by the Clinical Laboratory Improvement Amendments and accredited by the College of American Pathologists.

According to Dr. Krammer, the antibody test can, in some cases, pick up the body’s response to infection as early as three days post-symptom onset and is highly specific and sensitive. “We have shared the toolkit needed to set up the test with more than 200 research laboratories worldwide to help mitigate this global crisis,” Dr. Krammer says.

David L. Reich, MD, President of The Mount Sinai Hospital, and Judith A. Aberg, MD, Chief of the Division of Infectious Diseases and Immunology in the Department of Medicine, have led Mount Sinai’s convalescent plasma program. “The exchange of ideas between clinicians and scientists and our intense drive to innovate is the catalyst that led to this achievement,” says Dr. Reich. “Mount Sinai will continue to advance the science and medicine in the fight against COVID-19.”