Mount Sinai Actively Recruits Volunteers From Hardest Hit Communities for COVID-19 Vaccine Trial

Oct 5, 2020 | COVID-19, Engagement, Featured, Research, Vaccines

WillieBenjamin Loadholt, right, undergoes a checkup from Kiwan Stewart, RN, at The Mount Sinai Hospital prior to receiving his second injection as a participant in the phase 3 clinical trial for Pfizer’s COVID-19 vaccine.

Participating in the Mount Sinai Health System’s clinical trial for the Pfizer COVID-19 vaccine has been deeply personal for New York City educator WillieBenjamin Loadholt. He says it has provided him with the opportunity to be proactive, to contribute to a potential solution that could put an end to the COVID-19 pandemic, which has been “devastating to the African American community.”

For months, Mr. Loadholt says, “Every time I would go on a friend’s Facebook page I would see, ‘We regret to announce the passing or the transition of this person or that person.’ A friend of mine owns a funeral home and they were doing so many funerals. This one’s mom passed away, or this one’s father or sister passed away. It was heartbreaking.”

So, in August, when a friend told him about the Pfizer COVID-19 vaccine trial at Mount Sinai, Mr. Loadholt was eager to sign up. “We want to know what’s going on,” he says. “People perish from a lack of knowledge. How can we avoid this? How can we get solutions for this?” Participating in the search for answers to the COVID-19 pandemic is “worthwhile because I am able to help myself as well as my community. We can’t get this if we don’t help each other.”

Mount Sinai is actively recruiting volunteer participants in communities of color. “We want to make sure the trial is representative of the people who were hardest hit by COVID-19,” says Debbie Lucy, Program Manager for the Mount Sinai Health System’s COVID Clinical Trials Unit. Based on a legacy of mistreatment and longstanding inequities in access to health care, Black Americans, in particular, are more hesitant than other groups to embrace the use of experimental vaccines and therapies.

Debbie Lucy

In August, Ms. Lucy and her team began handing out information about the vaccine in the communities around The Mount Sinai Hospital, between 96th and 105th Streets, east of Park Avenue. In fact, Mr. Loadholt found out about the clinical trial from a friend who lives in the area and received a knock on his door from Mount Sinai.

“We have teams of people who are out in different areas trying to educate people and get them involved. We are talking to people, handing out flyers, and making as many connections as we can,” says Ms. Lucy. “We’re going to different grocery stores, hair salons, nail salons, laundromats, restaurants—any place where we think people of color are either working or going to.”

When Ms. Lucy met a man who told her that his family did not have any masks, she says she called up a team member who immediately brought several masks to the corner of East 103rd Street where they were standing. “He was in awe that we went the extra mile to do that for him,” Ms. Lucy says. “For him it was more than the masks we gave him; it was the fact that we connected with him and met his need immediately. We stood out there and talked with him and gave him additional information about participating in the trial.”

Mount Sinai has also held community forums that educate people of color about the Pfizer vaccine trial. In September, Mr. Loadholt discussed his experience at one of these forums. Ms. Lucy says, “We believe it’s easier for people who look like you to talk with you about participating in a trial because we recognize that there’s a lot of mistrust around research among people of color. Our ultimate goal is to find a vaccine that’s going to help prevent COVID-19, but with any trial we also want to test for safety to make sure it’s not causing any negative side effects in people, and that it’s well tolerated.”

Of the more than 180 COVID-19 vaccines under development, Pfizer’s RNA vaccine is one of the furthest along in the phase 3 clinical trials taking place at Mount Sinai and other locations throughout the United States. The vaccine is based on new technology and can be produced completely in vitro, or in a laboratory.

“I am grateful to individuals like Mr. Loadholt who are participating in this vaccine study and helping us to inform others,” says Judith A. Aberg, MD, the Dr. George Baehr Professor of Clinical Medicine, and Chief of Infectious Diseases for the Mount Sinai Health System. “Involvement with communities should not be overlooked due to false assumptions that people of color are unwilling to enroll in clinical trials. Such false assumptions result in harmful health disparities. We must provide everyone with the opportunity to participate in clinical trials and receive linkage to care. Only through engagement and education can people protect themselves and their loved ones.”

After receiving his second of two injections in September, Mr. Loadholt says he feels fine. He does not know whether he received the real vaccine or a placebo, which is how the placebo-controlled, randomized, observer-blinded vaccine trial is designed. He will be able to find this out in two years. “If I did receive a placebo, at least I can help another person of color receive the real one,” he says.

Mount Sinai has provided Mr. Loadholt and other trial participants with either an iPhone app or their own separate device to communicate any symptoms. “The staff at Mount Sinai has been wonderful,” Mr. Loadholt adds. “I would like Mount Sinai to do what they’re doing and be a beacon in the community.”

To potential volunteers, he says, “Don’t be afraid. Try it.”

If you are interested in volunteering for a COVID-19 vaccine clinical trial, please call 212-824-7714 or email: COVIDTRIALSINFO@MOUNTSINAI.ORG. Mount Sinai offers $119 in compensation for all visits related to the clinical trial. Watch the following video to learn more

Watch a video to learn more about our clinical trial
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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 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.”

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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.

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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.”

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Vaccines for COVID-19: How Protective Are They? When Will They Be Ready? A Leading Vaccinologist at Mount Sinai Weighs In

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

Florian Krammer, PhD

As the SARS-CoV-2 virus circulates throughout the world unchecked, researchers are racing to develop more than 135 vaccines. How well will these vaccines work and how soon will we be able to benefit from them? To answer these questions and more, Mount Sinai Today turned to a leader in SARS-CoV-2 antibody research, Florian Krammer, PhD, Mount Sinai Professor in Vaccinology at the Icahn School of Medicine at Mount Sinai. Dr. Krammer is an experienced virologist whose Mount Sinai lab is working on a universal flu vaccine.

What does the vaccine landscape look like?

Vaccines have been made in record time, and they use different platforms. Two candidates use RNA technology, which has never been used in a vaccine before. Typical vaccine development can take up to 15 years but this is now getting shortened to months. Right now, there are more than 20 candidates already in clinical development around the world. Five of these are being developed in the United States. This makes me happy because there is not a single vaccine that can meet the entire demand of the market and if some fail there are alternatives.

Do any of the vaccine candidates look promising?

I am very positive about what we are seeing so far. We’ve seen pretty encouraging results from preclinical models, the phase 1 and phase 2 trials. But none of this means anything yet because the proof will be in the results from the phase 3 trials. That’s where we will learn about the actual efficacy and safety. In terms of efficacy, I don’t think we will end up with a vaccine that gives us 100 percent protection from infection (meaning sterilizing immunity). But we do not need a perfect vaccine, and I am relatively hopeful that several vaccine candidates will lead to solid protection from disease. I think a vaccine will probably also dampen transmission. This will help people who aren’t able to get vaccinated or mount a strong response after they are vaccinated.

When can we expect to see phase 3 trials?

Phase 3 trials are already ongoing. I assume we’ll have pretty good data sets by late fall or early winter, especially from interim analysis of the phase 3 trials. It’s very important that we don’t cut corners in terms of safety or efficacy even if countries like Russia are licensing vaccines right now, and China is giving its vaccine to the military. We really need to see what the phase 3 trials tell us and we need to rely on the U.S. Food and Drug Administration to make a judgment call and only license vaccines that are safe and that work even if they are not perfect in terms of efficacy.

What can go wrong in a phase 3 trial?

If you don’t see efficacy, you don’t go forward. A lot of other things can go wrong. Vaccines can trigger an unintended neurological issue or an autoimmune disease in rare cases. You wouldn’t see this in a few hundred people in phase 1/2 trials, but you would see one, two, or three cases in a few thousand people. An example of this happened in 1976, after an outbreak of swine flu among soldiers at Fort Dix, New Jersey, led to massive vaccination campaigns and increased cases of Guillain-Barré syndrome.

Do we know how the vaccines will work in children or the elderly?

All COVID-19 vaccines tested so far in the clinic show relatively high but acceptable reactogenicity—adverse reactions, including fever and a sore arm at the injection site. Since there is often a lot more reactogenicity in kids than in adults, we need to see if that is also an acceptable level in children. In terms of age de-escalation, I’m not sure what the vaccine producers are planning for phase 3 trials. Typically, you would start testing in healthy young adults and work your way down in age. But if you see a safety signal that’s unacceptable, you may end up with a vaccine that is licensed for adults but not below a certain age group in children. I am not too worried about safety in older people but I am worried about their immune response. We know we have a lot of trouble inducing immune response with flu vaccines in older people and we even have special vaccine formulations for that age group. It’s not clear if we will run into the same problems with COVID-19 vaccines. Some of the phase 3 trials will include people in their 70s, up to 80, so this is something we should know about soon.

What could complicate the rollout of an effective vaccine?

Large-scale production is difficult, and a couple of front runners in this race have never produced a vaccine for the market. A lot of the technologies being used are new and there is little experience with scaling them up. Also, we don’t know who will get the vaccine first. Probably health care workers and high-risk individuals, but I would like to see a discussion about this and understand what the public thinks. Also, distribution and administration of that many vaccine doses needs to be coordinated well and will be a huge effort. You also have to take into account that there will not be instantaneous protection. You may need two shots, and it could take a few weeks to a month until you mount protective immunity. In the United States alone we will need 660 million doses (two shots per person). Globally, we will need 16 billion doses. It’s almost unimaginable how much vaccine we will need.

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