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Mount Sinai Scientists Find Children with COVID-19-Related Illness Display a Unique Pattern of Immune Responses

Sep 28, 2020 | COVID-19, Featured, Research

In Mount Sinai’s study, the children were age 12 on average and otherwise healthy.

MIS-C is a rare, potentially life-threatening syndrome that occurs about five weeks after children have been infected by the SARS-CoV-2 virus, which causes COVID-19. Most of the children are actually asymptomatic for COVID-19, but when they develop MIS-C they are hospitalized with shock, excessive blood clotting, gastrointestinal symptoms, and heart dysfunction.

In a new development, researchers at the Icahn School of Medicine at Mount Sinai have identified a unique pattern of immune responses that characterize multisystem inflammatory syndrome in children (MIS-C) and could eventually serve as a biomarker, or reliable indicator that would help diagnose the disease.

The Mount Sinai scientists discovered this unique pattern of immune responses by using sophisticated single-cell technology to analyze the blood circulating through the bodies of nine MIS-C patients who were treated at Mount Sinai Kravis Children’s Hospital between late April and June 2020. The researchers found elevated levels of specific cytokines—molecules that regulate immunity and inflammation—and chemokines—signaling proteins—that distinguished the MIS-C patients. The children were age 12 on average, otherwise healthy, and almost equally divided between boys and girls.

“In order for us to really understand MIS-C, we had to describe the disease, and this is the first in-depth mapping of what the disease looks like,” says Dusan Bogunovic, PhD, Associate Professor of Microbiology, and Pediatrics, and Director of the Center for Inborn Errors of Immunity, part of The Mindich Child Health and Development Institute and Precision Immunology Institute. Dr. Bogunovic is the corresponding author of a Mount Sinai study that describes the findings in detail. The paper was posted to the pre-print server medRxiv.org last summer and is now published in Cell.

Dusan Bogunovic, PhD

Conor Gruber, an MD/PhD candidate at the Icahn School of Medicine, a member of the Bogunovic lab, and the paper’s first author, says, “We have mapped autoimmune parameters at an unprecedented level. Now we need to know if this autoimmune component causes the disease or is just a byproduct of MIS-C. We’re actively researching this.” Autoimmunity occurs when an individual’s antibodies mistakenly attack their body. Since the body’s adaptive immune response to disease usually forms after several weeks—the same amount of time it takes for children to develop MIS-C—the researchers believe this is likely where the problem lies within the immune system.

When the initial cases of MIS-C began surfacing in the spring, several weeks after the surge of adult COVID-19 cases in the New York metropolitan area, MIS-C was considered an atypical form of Kawasaki disease, an acute systemic inflammation of the blood vessels, mainly affecting very young children. Since then, the World Health Organization has classified MIS-C as a distinct syndrome. The Mount Sinai study found that “overlapping features are striking, suggesting that MIS-C may lie along a spectrum of Kawasaki disease-like pathology.”

Although further studies into the causes of MIS-C are needed, says Dr. Bogunovic, the good news is that widely accepted protocols are in place for the successful treatment of the disease. He is less certain, however, about whether a child’s predisposition to MIS-C portends a predisposition to different autoimmune disorders down the line or will interfere with the ability to successfully receive a COVID-19 vaccine.

“All of these postulates need careful, methodical, and well-controlled experimental dissection,” the study authors wrote. “Until then, MIS-C remains scientifically puzzling, but therapeutically manageable.”

Mount Sinai Helps Ensure the US Open Is a Memorable Event

Sep 17, 2020 | Community, Featured

At the US Open are, left to right, Aruna Seneviratne, MD; Melissa Leber, MD; Alexis Colvin, MD; James Gladstone, MD; and Shawn Anthony, MD, MBA

The 2020 US Open Tennis Championships was a memorable event thanks to prevention strategies to decrease the risk for transmission of COVID-19 from a team of infectious disease experts, orthopedic surgeons, sports medicine physicians and musculosketal radiologists at Mount Sinai Health System who collaborated with the USTA to create a comprehensive health plan to guide athletes in safely playing at this year’s tournament. Mount Sinai served as the official medical services provider for the eighth consecutive year at the tournament.

In this post, Melissa Leber, MD, Director of Emergency Department Sports Medicine at Mount Sinai, and Associate Professor of Sports Medicine and Emergency Medicine, Icahn School of Medicine at Mount Sinai, and US Open Player Physician, reflected on the experience.

As a longtime player physician at the US Open, as well as at the Western and Southern Open this year which took place in New York due to the pandemic, I am not surprised by how well things went. The amount of careful thought and organization that went into the safe operation of these two tennis tournaments is not only inspiring but also comforting. I have a front row seat to the intricacies of creating these safe environments and the effort it takes from all involved to make sure it remains that way. My colleague Alexis Colvin, MD, Chief Medical Officer of the US Open, has worked tirelessly for weeks to bring the first major tennis tournament of 2020 to New York.

This is my eighth year taking care of the elite athletes at the US Open. This job has always been, and will continue to be, high pressure, having to take care of the world’s best tennis players, making highly scrutinized quick decisions while on a court in front of thousands of eyes. But this year is different. From a medical standpoint, we know that many Covid-19 symptoms mimic other medical problems that we encounter frequently in tennis, such as heat illness, dehydration, allergies, and the common cold. This makes diagnosis and care of the athletes that much more complicated.

Watch the closing ceremonies, which featured Mount Sinai’s doctors

The grounds of the National Training Center were eerily quiet and none of us can wait for fans to return. Balancing not only the athletes’ physical needs and their emotional well-being takes special considerations. Bringing a little bit of New York to the athletes who have traveled from around the world is a special focus this year. We had local food trucks and entertainment so that the athletes can have an outlet after practicing and playing all day.

In addition to Dr. Colvin and Dr. Leber, Mount Sinai physicians supporting the 2020 US Open include:

Lisa Anthony, MD, Assistant Clinical Professor in Dermatology, Icahn School of Medicine at Mount Sinai

Shawn Anthony, MD, MBA, Assistant Professor of Sports Medicine and Orthopedic Surgery, Icahn School of Medicine at Mount Sinai; medical director for Broadway shows

Carlos Benitez, MD, Director of Musculoskeletal Imaging, Mount Sinai West and Mount Sinai St. Luke’s; and Associate Professor of Radiology, Icahn School of Medicine at Mount Sinai

Bernard Camins, MD, Medical Director of Infection Prevention, Mount Sinai Health System

Jeffrey Ciccone, MD, Assistant Professor of Anesthesiology, Perioperative & Pain Medicine, Icahn School of Medicine at Mount Sinai.

Houman Danesh, MD, Associate Professor of Anesthesiology, Perioperative & Pain Medicine, Rehabilitation & Human Performance, Icahn School of Medicine at Mount Sinai

Etan Dayan, MD, Assistant Professor of Diagnostic, Molecular and Interventional Radiology, Icahn School of Medicine at Mount Sinai

James Gladstone, MD, Chief of the Sports Medicine Service, Mount Sinai Health System; and Associate Professor of Orthopedic Surgery at the Icahn School of Medicine at Mount Sinai

Kevin Munjal, MD, MPH, MSCR, Associate Professor of Emergency Medicine, Population Health Science and Policy, Icahn School of Medicine at Mount Sinai

Trevor Pour, MD, Assistant Professor of Emergency Medicine, Icahn School of Medicine at Mount Sinai

Christopher Reverte, MD, Assistant Professor of Emergency Medicine, Icahn School of Medicine at Mount Sinai

Aruna Seneviratne, MD, Associate Professor of Orthopedic Surgery, Icahn School of Medicine at Mount Sinai

Eric Small, MD, Assistant Professor of Pediatrics and Orthopedics, Icahn School of Medicine at Mount Sinai

Watch a series of videos featuring Mount Sinai experts at the US Open

Mount Sinai Lab Creates Shared Database to Help Scientists Find Drugs That Can Be Used to Treat COVID-19

Sep 17, 2020 | COVID-19, Featured, Research

Avi Ma’ayan, PhD

As the public turns its attention to vaccine development in the hope of ending the COVID-19 pandemic, equally important work is taking place in the area of drug repurposing—identifying drugs already approved for other diseases that may also be effective for COVID-19. Repurposed drugs offer a safe and relatively quick and inexpensive treatment route.

At the Icahn School of Medicine at Mount Sinai, a team of researchers led by Avi Ma’ayan, PhD, Director of the Mount Sinai Center for Bioinformatics and Professor of Pharmacological Sciences, is investigating drugs with the most potential. To that end, they created the COVID-19 Drug and Gene Set Library, a crowdsourced database and website that consolidates information from multiple labs around the world that performed in vitro COVID-19 drug screens. These in vitro tests are performed in a petri dish, which is the first stage in drug discovery, before the drugs are tested in animal models and then in human clinical trials. The website is available to all scientists who want to compare drug screen “hits,” and has drawn 2,000 viewers since it was launched in April.

“Drugs are just as important as vaccines and offer a solution for dealing with this pandemic,” says Dr. Ma’ayan. “The hope is that we’ll find a drug, or a combination of drugs, that people can take after they’re infected with the virus to block the virus from spreading and enable them to mount an effective immune response.” After all, he adds, not everyone may be eligible to receive a vaccine, based on their health profile, and even with a vaccine there will be people who get COVID-19 and need treatment.

Venn diagram shows some overlap in a set of drugs relevant to COVID-19 research

In September, the journal Patterns, a Cell Press publication, published an article that described the Ma’ayan Laboratory’s work on the project. The article described the lab’s machine learning approach, which explored approximately 200 “positive hit” drugs that were identified as inhibiting the SARS-CoV-2 virus, which causes COVID-19, from infecting human cells in vitro. Based on the shared biological and chemical properties of these drugs, the machine-learning model prioritized these drugs further and predicted additional compounds with similar properties.

“When you start synthesizing data from multiple studies, you look for consistency and seek to identify interesting mechanisms,” he says. “We want to understand the mechanism of action of those drugs. Why do they work? What are the pathways they affect? What are the targets of those drugs so we can better understand the lifecycle of the virus?” Currently, the laboratory led by Benjamin tenOever, PhD, Director of the Virus Engineering Center for Therapeutics and Research at the Icahn School of Medicine at Mount Sinai, is conducting experiments to further explore some of these questions in collaboration with Dr. Ma’ayan.

According to Dr. Ma’ayan, the COVID-19 Drug and Gene Set Library organizes information in a way that can be clearly summarized and reused at a crucial time in COVID-19 research, when time is of the essence. The library allows the scientific community to work together toward a cure and avoid promoting drugs that are not fully validated, which happened last spring with hydroxychloroquine.

“The website that we built is supposed to be unbiased,” he says, “and it looks at evidence in a way that offers consistency across the studies, where the right answer comes up in a more distributed, democratic way.”

When considering promising drugs Dr. Ma’ayan points to the example of HIV, a virus for which there is no vaccine, but many combinations of drugs that effectively keep the viral load very low and prevent new infections. These drug “cocktails” have helped improve the lives of many people around the world. “There are fewer people dying from HIV because of these drugs,” he says. “It’s not guaranteed we’ll have a vaccine for COVID-19 that’s 100 percent effective or even 50 percent effective, and there are people who aren’t going to be able to receive the vaccine. If people get sick from COVID-19 and you have drugs that can treat them, you could turn it into a disease that more people can recover from.”

Mount Sinai Leaders Explore COVID-19 Vaccines, Treatments, and the Path Ahead in Aspen Ideas: Health Panel Discussion

Sep 17, 2020 | COVID-19, Featured, Research, Vaccines

Does convalescent plasma therapy work? Is a successful vaccine for COVID-19 on the way? Will it be suitable for senior citizens and available to minority communities that were hardest hit by the pandemic? These pressing topics are explored in a recent Aspen Ideas: Health panel discussion that was led by Kenneth L. Davis, MD, President and Chief Executive Officer of the Mount Sinai Health System. Mount Sinai’s renowned vaccinologist Florian Krammer, PhD, and infectious disease specialist, Judith A. Aberg, MD, weigh in with informative answers to some of the nation’s most important health care questions.

“Many vaccine trials fail,” says Dr. Krammer, “but if you go with diverse approaches to creating a vaccine, it is very likely that one or even more of these will succeed.” With regard to convalescent plasma therapy, Dr. Aberg says, timing is everything. Administer the treatment early on before patients develop their own antibodies. Mount Sinai, she adds, is educating at-risk communities about the need for COVID-19 vaccines. When vaccines are ready to be administered Mount Sinai will be there.

To learn more about the most promising vaccines under development, why the infection rate in New York City is relatively low at this time, and whether we should be concerned about mutations to the SARS-CoV-2 virus, go to Aspen Idea’s Perspectives in Health.

New York Eye and Ear Infirmary of Mount Sinai, America’s First Specialty Hospital, Celebrates 200th Anniversary

Sep 10, 2020 | Community, Featured, MSBI

From left: James Tsai, MD, MBA, President of New York Eye and Ear Infirmary of Mount Sinai (NYEE); Daniel Laroche, MD, Assistant Clinical Professor of Ophthalmology; and Tamiesha Frempong, MD, Assistant Professor of Ophthalmology, Pediatrics, and Medical Education, were among those who gathered for the dedication of a portrait of David Kearny McDonogh, America’s first Black ophthalmologist and a former slave, who was trained at NYEE.

The New York Eye and Ear Infirmary of Mount Sinai (NYEE), in August, celebrated its 200th anniversary and its unique place as America’s first specialty hospital, which continues to provide patients with the highest level of care.

“As we enter our third century, we continue to innovate and lead in clinical care, education, research, and community service,” says James Tsai, MD, MBA, President of NYEE. “NYEE has really been ahead of its time and I think this is something we can be proud of in our bicentennial year.”

Indeed, the hospital’s remarkable history includes a significant chapter in American history and demonstrates the open-mindedness of its two young founders, Edward Delafield, MD, and John Kearny Rodgers, MD, who educated the nation’s first Black ophthalmologist, a former slave named David Kearny McDonogh. Dr. McDonogh’s professional path was laden with obstacles. After being allowed to unofficially attend and complete his medical studies at what is now Columbia University, he was denied his medical degree. But at NYEE, Dr. Rodgers provided him with the opportunity to become an eye doctor and practice his craft as a full staff member of the hospital, then located in a small suite in lower Manhattan. In a tribute to his mentor, Dr. McDonogh adopted “Kearny” as his middle name.

In August, as part of NYEE’s bicentennial celebration, a painting of Dr. McDonogh was hung in NYEE’s new surgical waiting room with a limited group of faculty and staff in attendance due to COVID-19 restrictions. No photos of Dr. McDonogh are known to exist. The painting by Leroy Campbell was commissioned by Daniel Laroche, MD, Assistant Clinical Professor of Ophthalmology at NYEE. At the gathering, Dr. Laroche called Dr. McDonogh “an American hero.” As far as we know, Dr. McDonogh is the only American enslaved person to have gained a professional medical education, says Dr. Laroche. “His story shows you cannot suppress the soul of man.”

Today, NYEE runs the nation’s largest ophthalmology residency program, with 10 residents a year, and continues to “look for the best trainees regardless of race, religion, ethnicity, national origin, disability, sex, gender identity, or sexual orientation,” says Dr. Tsai. “We are open to new ideas and focused on training the most qualified individuals, and committed to recognizing the talent and skills of these applicants. We have an incredibly diverse residency class. Drs. Delafield and Rodgers believed in providing expert care to patients from all walks of life so they could enjoy good health and lead productive lives. That is so much in line with the philosophy of the Mount Sinai Health System—that same willingness to take care of everyone.”

In keeping with its tradition of innovation, NYEE in July became the first U.S. hospital, and third in the world, to acquire a microsurgical robot for ophthalmology and study its future use in patients. The device is expected to provide surgeons with a significantly higher level of precision when performing procedures. NYEE has applied to the U.S. Food and Drug Administration for permission to use the robot for research and educational purposes and for clinical trials before expanding its use into retinal or other ophthalmic surgeries. Only two other microsurgical robotic eye systems exist in the world—in England and the Netherlands.

NYEE is also pioneering the use of telemedicine in ophthalmology by exploring new technologies and methods to permit eye doctors to make diagnoses using computers and artificial intelligence. The hospital is working with emergency room doctors and nurses within the Mount Sinai Health System to handle patients with eye emergencies more efficiently when an ophthalmologist is not physically present but is available remotely. The Emergency Department staff would conduct an eye exam and assist the ophthalmologist in making a diagnosis via remote diagnostics, rather than having patients wait a lengthy period of time before a specialist is able to get to the hospital.

Dr. Tsai says, “NYEE may look very different in our third century of service to the community. We will incorporate more telemedicine into our offering. We will also train doctors more effectively using the latest technology. But we will still possess the same ethos, culture, vision, and mission that have guided us since our founding 200 years ago.”

Men Hospitalized for COVID-19 Were Younger and Healthier Than Women Who Were Hospitalized

Updated on Jun 30, 2022 | COVID-19, Featured, Research

Men who were hospitalized for COVID-19 in New York City during the early days of the pandemic were both younger and healthier on average than their female counterparts, according to a new study by researchers at the Icahn School of Medicine at Mount Sinai. The study, posted to the preprint server medRxiv, analyzed the electronic health records of 3,086 racially diverse COVID-19 patients who were admitted to five hospitals within the Mount Sinai Health System on or before April 13, 2020, and followed through June 2, 2020.

“Just being male seemed to be a risk factor in and of itself,” says the study’s first author, Tomi Jun, MD, a hematology and medical oncology Fellow at The Tisch Cancer Institute of the Mount Sinai Health System. Members of Mount Sinai’s Department of Genetics and Genomic Sciences, and Scientific Computing and Data Science, also contributed to the study.

Of those requiring hospitalization, 59.1 percent were male with a median age of 64, vs. 74 years of age for women. While the men were more likely to have a history of smoking, the women were more likely to have pre-existing comorbidities such as hypertension, diabetes, chronic obstructive pulmonary disease and asthma, and obesity. The mortality rate for men and women was equal.

Tomi Jun, MD

“This was during the early days when there was a surge of cases in New York and we did not have effective treatments,” says Dr. Jun. “Looking at the data, there were a disproportionate number of men being hospitalized. And these men seemed to be healthy enough to do well with COVID-19, because we know that older age and having more comorbidities are associated with worse outcomes. When you take all those things into account, being male seemed to increase your risk.”

Kuan-lin Huang, PhD, Assistant Professor of Genetics and Genomic Sciences, and the study’s senior author, says, “We know there are a lot of hormonal and immunological differences between men and women. There are certain genes on the X chromosome that are involved in the immune system and women have two X chromosomes. Women go through pregnancy, which can have strong effects on the immune system. And we know that women are at higher risk of developing an autoimmune disease. Likely, it’s a complex set of these factors that contributed to the results. Specifically what is it? I don’t think anyone knows for sure. But that is what we were trying to get closer to with this and subsequent studies.” Understanding the underpinning of why this is happening at the molecular level, he adds, will provide insights into potential treatments.

Kuan-lin Huang, PhD

The researchers found interesting results when they examined data about the patients’ blood. “COVID-19 is very inflammatory and all of the hospitalized patients had very high markers of inflammation,” says Dr. Jun. “But we observed that women tended to have lower markers of inflammation than men. We conducted exploratory analyses to look at how predictive these markers were for death and found that in some cases higher markers for inflammation were associated with higher risk in women than men. So, although women, in general, had less inflammation than men when they entered the hospital, having higher indicators of inflammation seemed to confer a greater risk for them.”

Dr. Huang says the current study is a jumping-off point for future investigations that was made possible by Mount Sinai’s policy of allowing its data and clinical scientists to access the electronic health records.

“If our hospitals hadn’t taken care of all these patients and we didn’t know their histories we wouldn’t be able to do this research,” he says. “We really hope this will lead to more precise patient management. We should have different considerations for men and women when we think about whether that may add on to the risk of a COVID-19 patient.”