Mount Sinai Develops ‘Pseudo Virus’ to Assess the Effectiveness of Antibodies

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.”

Will Using A Steroid-Based Nasal Spray Increase My COVID-19 Risk?

The Centers for Disease Control and Prevention considers those who are actively being treated with high-dose corticosteroids to be immunocompromised. Most nasal sprays for allergies do not fall into this category. Consult your primary care physician regarding the specific medication you are taking.

Allergy sufferers are hyperaware of every cough, sneeze, and sniffle entering the height of this allergy season. Those with allergies are not only concerned with distinguishing their allergy symptoms from the novel coronavirus that causes COVID-19, but many are now worried that the medications they take to manage their symptoms might put them at increased risk.

Steroid-based nasal sprays have come under particular scrutiny because the active ingredient—corticosteroids—can reduce the strength of the body’s immune system, which is concerning during a pandemic. Fortunately, nasal spray users need not worry. Anthony Del Signore, MD, PharmD, Director of Rhinology and Endoscopic Skull Base Surgery at Mount Sinai Downtown-Union Square, explains why allergy sufferers should keep using their medications.

Should I stop using my steroid-based nasal spray?

If patients are getting the relief that they usually receive from taking these medications, I typically say to continue using them. Often, symptoms of nasal drainage, nasal obstruction, or sinus infections will increase if you come off of the medications.

It is also important to remember that with topical intranasal sprays, as well as topical nasal rinses with steroids in them, the absorption of the steroid is quite low. And, there is conflicting evidence as to whether or not steroids taken this way will actually cause any decreased defense against the virus.

A lot of the data and recommendations that we’re getting is for systemic steroids, which are steroids taken by mouth or administered intravenously. That’s where we are seeing the decrease in the immune system.

As a result, I am staying away from prescribing oral steroids for the time being. But topical nasal sprays, as well as topical rinses, I’m okay with.

I take an allergy pill. Are there steroids in my medication?

We do not typically give oral steroids to patients complaining about the typical symptoms of seasonal allergies. Instead, we recommend nasal rinses/netipot, oral antihistamines, and intranasal antihistamines as well as intranasal steroids, with pretty good effect and results.

Oral steroids are usually reserved for more serious conditions like asthma, lupus, or severe systemic allergic reactions. And, if you have a more serious condition that requires the use of these oral steroids, you have to weigh the risks and the benefits. I would counsel these patients to practice social distancing, good hygiene, and taking other precautions. These preventative measures can often tip the scale so that the benefits outweigh the risk of the steroids.

What should patients do if they are concerned that their medications will decrease their ability to fight off COVID-19?

There’s a lot of information out there, and patients may be having a tough time finding the right answers. If patients have any questions during these tumultuous times, they should consider setting up an in-person or telemedicine appointment to talk with their health care provider. After getting a global view of the patient and seeing what other risk factors they have, proper recommendations can be made that may at least help to put fears at ease at a time that’s very uncertain for many.

Mount Sinai Receives More than $1.2 Million for Front-line Workers From Online Charity Poker Event

A unique online fund-raising effort led by David Zaslav, President and Chief Executive Officer of Discovery Inc. and a Mount Sinai board member, has raised more than $1.2 million to support front-line staff at the Mount Sinai Health System.

The “All-In For Mount Sinai” celebrity poker tournament, held Saturday, April 25, included celebrities, leaders of business and finance, and Mount Sinai board members. All of the funds raised were donated to the Mount Sinai COVID-19 Response Fund, which will pay for personal protective equipment, meals, and other support for health care providers and other front-line workers at the Mount Sinai Health System.

The 65 participants included many figures from entertainment and sports: Ben Affleck, Bryan Cranston, Joy Behar, Bobby Flay, Chip Gaines, Cheryl Hines, Lorraine Bracco, Jason Alexander, Brad Garrett, Jordan Spieth, Adam Savage, Boris Becker, Bob Balaban, Shannon Elizabeth, Dr. Sandra Lee, Buddy Valastro, Mike Finnegan, Jesse James, Michael Symon, Dave Salmoni, Sig Hansen, Amanda Freitag, Tory Belleci, Will Packer, Suzanne Todd, Willie Garson, and Chris Harrison. Tiger Woods also supported the effort by announcing the tournament earlier in the week across his social channels, reaching millions.

In addition, David Solomon, Chairman and CEO of Goldman Sachs; Joe Kernen, host of CNBC’s Squawk Box; and Kevin Plank, founder of Under Armour, participated, along with Mount Sinai board members Richard Friedman, Frank Bisignano, and Robert Savage.

The donations came from 795 donors and were made via Pledgeling, an online company that helps businesses partner with nonprofits.

The event was hosted by Americas Cardroom, an online poker site.

Students, Postdoctoral Fellows, and Faculty Team Up to Advance Immunology Research on COVID-19

Members of the Sinai Immunology Review Project. From left to right: Matthew Spindler; Louise Malle; Berengere Salome, PharmD, PhD ; Miriam Merad, MD, PhD ; Luisanna Paulino; Verena van der Heide, PhD; and Nicolas Vabret, PhD. Via Zoom, left to right, top row to bottom: Alvaro Moreira, MD; Robert Samstein, MD, PhD; Rachel Levantovsky; Matthew Park, Conor Gruber; and Emma Risson.

The unprecedented generation of non-peer-reviewed scientific information about COVID-19 in just a few months helped galvanize more than 50 members of the Precision Immunology Institute at the Icahn School of Medicine at Mount Sinai into forming a group to parse through the data.

The effort, called the Sinai Immunology Review Project, is composed of faculty, postdoctoral fellows, and graduate students. By sharing their knowledge and expertise, project members evaluate the quality of the research being posted to the bioRxiv and medRxiv preprint servers and help advance the most significant findings that are related to their field. Peer review is quality control provided by a panel of experts who evaluate whether a study has used proper research methods and is scientifically valid.

“Reviewing the preprinted studies benefits the authors and the scientific community, provides the public with access to what is being discussed, and helps reinforce scientific credibility,” says one of the project leaders, Nicolas Vabret, PhD, Assistant Professor of Medicine (Hematology and Medical Oncology) and a member of the Precision Immunology Institute at the Icahn School of Medicine. “To help pick the best treatments for COVID-19 you need to have a strong understanding of the pathology of the disease and we are able to help with this.” Many of the researchers who are working from home during this pandemic welcome the collaborative opportunity to contribute to the field.

Since mid-March, the project’s participants have ranked more than 2,000 studies according to their immunological relevance and written 130 reviews that are then posted alongside the corresponding study on the preprint servers. To ensure that the best science is elevated, each summary is written by a fellow or student specializing in a specific area of the immune system and then reviewed by a faculty member. A website built by Nicolas Fernandez, PhD, a computational scientist at Mount Sinai’s Human Immune Monitoring Center, hosts all of the reviews.

Recognition of this work recently led the editors of Nature Reviews Immunology to reach out to Miriam Merad, MD, PhD, Mount Sinai Professor of Immunology and Director of the Precision Immunology Institute, to form a unique collaboration. Mount Sinai is now publishing three short commentaries in the publication each week on the most promising immunological findings on COVID-19.  Within a few days of launching the collaboration with Nature Reviews Immunology, Mount Sinai’s work was viewed more than 10,000 times.

Project co-leader Robert Samstein, MD, PhD, Assistant Professor of Radiation Oncology, and a member of the Precision Immunology Institute, says, “This has been a massive effort. It’s been a great opportunity for Mount Sinai’s trainees to integrate all of their knowledge and provide a summary for the scientific community,” so quickly and efficiently. “The huge flurry of output on COVID-19 by the scientific community is unprecedented and this effort is responding to that.”

While speed and the open sharing of information are vital to enhancing further understanding of the COVID-19 health emergency, the peer-review process is an essential part of scientific advancement and the preprint servers that are now publishing all of this new information were never meant as a replacement. In the absence of the peer-review process, members of the Immunology Project are stepping in to provide their expertise in the best way they can, says Dr. Samstein.

“By doing this we can really help make it easier for policy makers, physicians, and scientists to see what the best information is as it evolves and have a direct impact on treatments,” adds Dr. Vabret.

As time goes on, the medical and scientific community is learning more about the disease and calling into question some of its earliest hypotheses about possible treatments. This makes the need to highlight quality science to inform decision-making a continued priority, according to Dr. Vabret.

What are COVID Toes and Should I Worry about Them?

Doctors are reporting that they are beginning to see cases of “COVID toes,” red or purple patches on toes that some believe could be a sign of the novel coronavirus (COVID-19).

While the scientific evidence is still limited about what may be causing this medical condition, people who have this symptom should contact a dermatologist or their health care provider, according to Noelani Gonzalez, MD, a dermatologist and Director of Cosmetic Dermatology at Mount Sinai West in New York.

“Your doctor will follow up by asking you questions to try to figure out if this could be a possible sign of coronavirus or something else,” she said.

In fact, the patches on the toes resemble another condition called chilblains, also known as pernio, a painful inflammation of small blood vessels. People may often feel itching, stinging, or burning.

In most circumstances the condition resolves on its own and doctors recommend behavioral measures such as keeping your feet warm, but in persistent cases topical steroids can help reduce inflammation, and aspirin can help improve blood flow to your extremities. Fortunately, the condition tends to go away within a few days or up to two weeks, according to Dr. Gonzalez.

This is a condition doctors typically see in the colder months, which is one reason why the recent reports, while the weather is warming, may be an indication of something different, she said.

In order to gather better information, the American Academy of Dermatology recently started a COVID-19 Registry to collect reports of this condition from physicians and health care professionals so that they can be studied, and to avoid the spread of medical misinformation.

Dr. Gonzalez says “COVID toes” has been found among people of all ages, though many of the cases have been among children and young adults. Doctors believe that may be because younger people typically mount more aggressive immune responses to a virus or other infection.

Doctors say this type of inflammation in “COVID toes” can be caused by the inflammation caused from the immune response to the virus, by an inflammation in blood vessels, or by clotting in blood vessels, or even by a combination of these, but there is not yet a definitive answer.

My Child’s MMR2 Vaccine Has Been Delayed Due to COVID-19. Should I Be Concerned?

The novel coronavirus (COVID-19) pandemic has postposed many important events, including your child’s immunizations. The MMR2—the second shot of the measles, mumps, and rubella vaccine—is particularly important for New York area parents who remember the past year’s measles outbreak. Stephen Turner, MD, Medical Director, Mount Sinai Doctors Brooklyn Heights, explains why parents need not worry if their child’s vaccination has been postponed.

Should I be concerned about delaying my child’s second MMR?

Fortunately, we do not have any measles circulating in the population at this time. So, it is a very reasonable option to delay the second MMR until a parent feels comfortable going to the physician’s office and getting the vaccine. The second dose, although most frequently given at age four, is recommended to be given between ages four to six according to the Centers for Disease Control and Prevention immunization schedule, which gives a lot of flexibility for your child to be fully vaccinated on time. 

Will delaying the second MMR put my child at any increased risk?

The second MMR is not a booster dose; it is to increase the immunity rate among the population. After one dose of MMR, approximately 92 percent of people are immune to measles. The second dose increases the immunity rate to 97 percent or higher. Therefore, a child who has received one MMR is very likely already immune.

How long can the vaccine be delayed?

There is no limit to how long the MMR2 vaccine can be delayed. In general, vaccines have a minimum spacing but not a maximum spacing. So, if a second dose of a vaccine is supposed to be two months later, for example, and you came back in two years, you pick up where you left off and get the second dose. Your child will not have to restart the vaccine series.