Daniel Stadlbauer, PhD, a postdoctoral fellow in Florian Krammer’s laboratory, adds a substrate to an ELISA plate that indicates whether antibodies binding to the spike protein of the SARS-CoV-2 virus are present in a human serum sample. The deep yellow color indicates antibodies are present. No color means that antibodies are not present.
The majority of individuals with COVID-19—including those with mild infections—mount a robust antibody response that is stable for at least three months, according to a new study by researchers at the Icahn School of Medicine at Mount Sinai. This antibody response correlates with the body’s ability to neutralize or actually kill the SARS-CoV-2 virus.
Mount Sinai’s findings concur with studies conducted by major academic institutions elsewhere. Scientists have now had more than three months to track the levels of antibodies produced by individuals since the SARS-Co-V2 virus began to infect populations around the world.
“There were messages about the antibodies going away quickly. That’s not the case,” says Florian Krammer, PhD, Professor of Microbiology, Icahn School of Medicine at Mount Sinai, a senior author on the recent preprint study. “The take-home message is that it looks like a pretty normal immune response.” Dr. Krammer developed one of the first effective SARS-CoV-2 antibody tests, which received emergency use authorization from the U.S. Food and Drug Administration at Mount Sinai’s clinical laboratory.
Additional time will be needed to determine how protective those antibodies are and how long-lived they are beyond three months. So far, Dr. Krammer says, animal models show that antibodies to COVID-19 behave like typical antibody responses to other diseases, meaning they protect from reinfection. The same scenario is likely for the vast majority of individuals, he says. If people become infected again their symptoms would likely be less severe.
“You need to follow people to see how long the antibodies are stable. These studies require time and there will be more data as researchers look at antibodies after 3 months, after 6 months and then again after a year,” Dr. Krammer says. He and his colleague, Viviana Simon, MD, PhD, Professor of Microbiology, and Medicine (Infectious Diseases), at the Icahn School of Medicine at Mount Sinai, are doing exactly that. In a study called Protection Associated with Rapid Immunity to SARS-CoV-2 (PARIS), they are tracking the antibody levels of, approximately, 140 individuals over 12 months. “We examine the participants every two weeks so we get a very granular look at how the antibodies are moving,” Dr. Krammer says.
Within the human body there are several levels of defense. In a typical response, acute plasmablast B cells are generated within days of an infection. These first responders serve as the infantry and coalesce to make an initial bolus of antibody, but their strength soon wanes. Then the body’s immune system kicks in with long-lived plasma B cells, which provide antibodies over a long period of time, and memory B cells, which can respond quickly if the virus attacks again. COVID-19’s relatively long incubation period of upwards of 7 days, likely gives the body ample time to create antibodies quickly if a reinfection would occur.
In addition to these B cell antibodies, the human body makes memory T cells, which appear to be helpful in fighting off the SARS-CoV-2 virus. In fact, blood samples taken from individuals who survived the first SARS virus in 2002-2003—a coronavirus cousin of SARS-CoV-2—showed they still had active memory T cells 17 years later, according to the National Institutes of Health (NIH). Interestingly, the NIH reported that these memory T cells now also recognized part of the SARS-CoV-2 virus.
“There’s a lot of evidence that we see a normal immune response,” Dr. Krammer says. “Now that doesn’t mean we will all be protected forever. And it doesn’t mean that it’s impossible to get re-infected, specifically if someone is immune suppressed. We just don’t have that data yet. We will generate that data as we move forward.”
When Paul Levine, 86, began feeling sick, with chills, fever, and weakness, he feared his cancer might have returned, so he called his oncologist. After learning Mr. Levine had lost his sense of smell, a symptom of COVID-19, the doctor immediately sent him to the hospital, where he was diagnosed with the disease.
In the hospital, Mr. Levine felt miserable. He was put on oxygen and given infusions of fluids. He had trouble sleeping and didn’t feel like eating. He missed his wife, Sondra, who called several times a day, and he missed her cooking.
After about a week at Mount Sinai Beth Israel, he was able to return home to his East Village apartment to continue his recovery, thanks to a unique Mount Sinai program that offers hospital care in home settings.
Since 2014, Mount Sinai has offered some patients arriving at the hospital the option of getting the care they need at home under its Hospitalization at Home program. The program provides twice daily visits from nurses, a special digital tablet to communicate with the hospital, and the ability to receive all needed tests and exams, including IV infusions, ultrasounds, and supplemental oxygen.
Shortly after patients with COVID-19 began arriving at hospitals, Mount Sinai developed a new program, called Completing Hospitalization at Home, that allowed appropriate COVID-19 patients like Mr. Levine to be discharged to home to complete their recovery, while receiving all of the care they would normally receive in the hospital.
“I believe that the hospital at home program gave me the best of both worlds. I had hospital care with the home cooking that was most important in recovering the weight I had lost, along with my wife’s care and company,” says Mr. Levine, who lost about 18 pounds.
Almost three months after his initial diagnosis, Mr. Levine, a diabetic who recovered from treatment for a blood disorder called chronic lymphocytic leukemia (CLL) more than a decade ago, was doing much better. He still felt some shortness of breath, even with minimal exertion. But he’s thankful to be at home and to finally get his appetite back, especially for his wife’s homemade mushroom and barley soup.
Linda V. DeCherrie, MD, the program’s clinical director and a Professor in the Department of Geriatrics and Palliative Medicine at the Icahn School of Medicine at Mount Sinai, said the program helps patients recover because they are more comfortable and find it easier to gradually return to normal activities, such as walking around and getting a cup of coffee. Studies show these patients have better outcomes.
“You are in your own bed, eating your own food, and enjoying the company of your loved ones,” said Dr. DeCherrie. “Being at home can help your recovery in many ways.”
Our society is facing one of the greatest health challenges—the growth of the population of older adults. In less than 10 years, the number of persons over the age of 65 in the United States will exceed the number of people under 21 for the first time in history.
The recognition of this profound change in our society led to the founding of Mount Sinai’s Brookdale Department of Geriatrics and Palliative Medicine 38 years ago, and the Department’s focus on clinical care, research, and education has guided its growth ever since.
The Department’s vision and a commitment to innovation meant it was uniquely positioned when the COVID-19 pandemic hit New York City early this spring. In this Q&A, R. Sean Morrison, MD, the Ellen and Howard C. Katz Chair of the Brookdale Department of Geriatrics and Palliative Medicine, Icahn School of Medicine at Mount Sinai, explains how the Department responded and how its efforts helped save lives in New York and around the country.
The Mount Sinai Hospital Ranked Among Top in the Nation by U.S. News & World Report; Brookdale Department of Geriatrics and Palliative Medicine Claims No. 1 Spot in Specialty Rankings
But challenges remain. Dr. Morrison says older adults face unique concerns, as many must continue to live in isolation, while Mount Sinai and other health systems face concerns of their own, as health care workers continue to cope with the difficult demands of the pandemic.
R. Sean Morrison, MD
“Our Department is working very hard to identify ways to bring a social connection to our older adults who need to be physically distant. Their feelings of isolation are real, and those emotions are ones that we don’t yet have a good solution for,” says Dr. Morrison. “Also, as we emerge from the COVID-19 surge in New York City and, hopefully, avoid another surge in the fall, we need to think about the emotional health of our health care workers, because long after we have a vaccine for COVID-19, the after-effects of caring for people will be with us and with our health care workers.”
What is unique about the approach of your Department?
In 1982, the first Chair of this Department, Robert Butler, recognized that if health care in this country was going to match the needs of its citizens, the focus needed to be on developing leaders who could care for the special needs of older adults. This Department was founded on the principle that health care must meet the needs of the society, and it must adapt as the demographics of that society changed. Over the past 30 years, this Department has led innovations in health care for older adults, developing models to find age-friendly health care for people in hospitals and in ambulatory clinics, training the leaders who have gone out throughout the United States to establish divisions and departments focused on the needs of older adults. Our research has led to fundamental changes in how we think about care for our most vulnerable patient populations.
How did this track record help you respond to the COVID-19 pandemic in New York?
The work that this Department had done under the leadership of its founding chair Robert Butler, and my predecessor, Albert Siu, positioned us to respond to the needs of New York City in a way that I don’t think any other institution could. The data that we had from China, from Italy, and from other earlier hot spots made us realize that the population at highest risk for severe COVID, and indeed for mortality, was the group of people that we care for, those over the age of 65. From the time that first case was reported, we put together a plan to ensure that our population would be cared for, that they would be safe. And that we would have a plan in place to provide the medical care, the added layer of support to families, and the security that the New York City population needed as COVID ravaged through our city.
What specific steps did you take and how did that help?
First of all, we put in place a system to ensure that we touched every single patient in our ambulatory clinics, that we contacted every single patient to talk to them about their wishes for care, to talk to them about how to avoid COVID and how to stay safe, and what to do if they developed symptoms. We rapidly developed a system of telehealth so that we could care for our patients in their homes, without them having to leave that safety, and so that they didn’t have to have health care providers coming in to see them.
How did that work?
We provided telehealth through something as simple as a telephone call, through video conferencing, and over a number of different platforms. For those people who needed face-to-face, in-person care, we expanded our home-based medical care so that we could go to see them, and keep them safe, rather than have them come to the hospital.
What other steps did you take?
In our hospitals throughout the Health System, we embedded our clinicians into the teams that were responsible for caring for the incredible numbers of patients who were coming into the programs. We embedded our clinicians in the emergency departments. We embedded our clinicians in the intensive care units. We embedded our clinicians within hospital medicine. Wherever patients with COVID were treated within the Mount Sinai Health System, a member of our Department was there to ensure that their special needs were met. We developed some very new and innovative models of care delivery that we took from concept to innovation to scale in a matter of days, rather than a matter of months.
Can you give an example?
We created a 24-hour telephone hotline that allowed overextended and overwhelmed emergency physicians and intensive care unit physicians to refer patients to us, so we could discuss their goals of care with them. We could advise around symptom management, and we could provide support to their families who could not see them, because no visitors were allowed in any New York City hospital during this time.
How was the Department able to scale up so quickly?
I think it was really three key elements that this Department has been doing since its founding, namely our focus on clinical care, research, and education.
A key part of our mission is to create leaders, not just in the care of older adults, but leaders in health systems, leaders in hospitals, leaders in community centers. For example, the senior vice president of the Mount Sinai Health System, who was responsible for coordinating clinical care throughout the pandemic, was a graduate of our fellowship program. He knew the importance of high-quality care for older adults during this pandemic and made sure that the patients in the Health System received that care, and that our Department was on the front lines. It was leadership within the Department, graduates of our training program, who developed the innovations, who developed the care models, who understood the need, throughout the Health System, for high-quality care for older adults.
Our research has focused on how do you deliver high-quality care to people outside of the hospital, outside of doctor offices. That allowed us to create new models of care that met the needs of the population.
And it was our educational efforts. We knew how to train, very quickly, other clinicians who may not have had training in the appropriate care of older adults, or the special needs of older adults, and be able to put that on the ground, right away, when patients and families needed it most. This Department trains 1 in every 10 geriatricians in the United States. Our graduates are in hospitals and health systems throughout the country.
What was the result?
The models of care that we have developed at Mount Sinai have been implemented in hospitals and health systems throughout the country. The work of our educators, providing high-quality technical support for the care of older adults, have been disseminated throughout the country. As other parts of the country wrestle with the challenges of COVID and, unfortunately, as the number of cases rise in other cities, as our experience this spring is being repeated elsewhere, the work of this Department, I believe, will save many, many lives throughout the country because of what we did in New York City.
So what are you focused on now?
As New York City has emerged from the surge of COVID, I worry about a number of challenges that we are facing and will continue for us. These challenges affect our patients, and our health care workers.
For patients, there is a sense of isolation. In order for our patients to stay safe, they have had to remain in their homes, often alone or with very few visitors. There is a sense of loneliness, indeed, the sense of purpose may seem limited, given how much of their time is spent isolating at home. We must ensure that we recognize their mental health needs, identify when isolation and distress becomes major depression, and provide support that helps our patients through the next six to nine months before we have a vaccine.
And what about health care workers?
The second challenge that I think we all face is that of the emotional health of our health care workers. My faculty experienced and saw more death in three months then many clinicians will see in entire careers. They were often the person holding the iPad so that their patient could say goodbye to their families and loved ones, or could have a conversation, not knowing what was going to happen to them and not being allowed to have their family there. Our faculty, our clinicians, our staff became patients’ families. They did that every single day, hour after hour, minute after minute. And it takes its toll.
Sandra Sermone and her son, Tony, who has ADNP syndrome. Mrs. Sermone founded the ADNP Kids Research Foundation, which is funding Mount Sinai’s phase 2 clinical trial into the safety and efficacy of ketamine as a potential treatment.
Ketamine, an anesthetic medication that has also been approved for use in severe depression, is now offering promise to children with a form of autism known as ADNP syndrome, or Helsmoortel-Van Der Aa syndrome. Ten children, ages 5 to 12, will soon take part in a clinical trial conducted by the Seaver Autism Center for Research and Treatment at Mount Sinai to determine whether ketamine is safe and well tolerated, and able to help compensate for the neuropsychiatric deficits that stem from missing a copy of the ADNP gene.
This will be the first clinical trial launched for ADNP syndrome, which was identified in 2015. It is a testament to the dedication of parents and physicians at the Seaver Autism Center, and the potential of artificial intelligence (AI) in helping advance treatment research in rare disorders.
Ketamine and several other existing drugs were identified by an AI tool, mediKanren. It was created at the University of Alabama by a colleague of Matthew C. Davis, MD, whose child has ADNP syndrome. Dr. Davis and another parent, Sandra Sermone, investigated ketamine in relation to ADNP within the existing scientific literature and found that it upregulated expression of the gene. With this and other relevant clinical data in hand, they filed for intellectual property protection. Then Mrs. Sermone brought the information to leaders of the Seaver Autism Center, who agreed that it was worth further investigation. Alexander Kolevzon, MD, Clinical Director of the Seaver Autism Center applied to the U.S. Food and Drug Administration for permission to proceed with a clinical trial and received approval.
“We think ketamine has potential and that it’s safe, so we’re very excited about it,” says Mrs. Sermone, who founded the ADNP Kids Research Foundation in 2016. The Foundation recently ran a “virtual” fundraising effort that raised more than $150,000 in six weeks that will be used to finance the entire phase 2 clinical trial and begin to lay the groundwork for a possible phase 3 study.
Approximately 275 children worldwide have been diagnosed with the syndrome, which often is accompanied by other complex health issues of the heart and brain. “I am so grateful for the team at Mount Sinai. I’ve never seen a group more dedicated to working with patient groups,” she adds. “Ketamine is a repurposed drug, so if it shows efficacy we can hopefully move quickly into a larger, phase 3 clinical.”
Ana Kostic, PhD, Director of Drug Discovery and Development at the Seaver Autism Center, says, “Ketamine has been used for many decades. We know a lot about the molecule and its safety profile, and now to find new uses for it through scientific discovery is amazing.”
Since ADNP is very important for the development and function of the central nervous system, the ability to restore its functionality would be extremely beneficial.
Dr. Kolevzon says each of the children enrolled in the clinical trial will receive a single infusion of ketamine over a period of 40 minutes and will be monitored over the course of four weeks to assess improvement. In addition to determining its safety and tolerability, he says, “we are also really interested in clinical improvement. Kids with ADNP have a lot of sensory sensitivities that we can measure with different tools, such as electrophysiology.” This would enable the researchers to “see whether there are changes in the electrical patterns in the brain in response to ketamine, and that might give us insight into potential biomarkers. These children have language problems, behavioral problems, and sleep problems. There are a lot of issues that go along with ADNP syndrome that we’re hoping to potentially address.”
The promise of ketamine may also extend to larger populations of individuals with autism who do not necessarily have ADNP syndrome, according to Dr. Kostic. “It could have beneficial effects in people who don’t have the same mutation but who have similar deficits.”
Access to high-quality genetic technology has become increasingly affordable over the past several years and has enabled more families to receive accurate and earlier diagnoses of many disorders, including autism. In most cases, the younger a child receives intervention, the better their chances of improvement. Earlier diagnoses, and a potential treatment such as ketamine, provide Mrs. Sermone and other committed parents with hope.
“It’s incredibly important because, currently, there isn’t one single treatment for our children with ADNP syndrome,” says Mrs. Sermone. “Our kids don’t produce enough of the ADNP protein. It’s like they’re running on half a tank of gas. To improve the quality of their lives—for us, that would be amazing.”
The Graduate School of Biomedical Sciences at the Icahn School of Medicine at Mount Sinai conferred 201 master’s degrees during a ceremony that was held virtually on Friday, June 26, as New York City continued to observe masking and social distance protocols in the midst of the COVID-19 pandemic. The Graduate School now has eight master’s degree-granting programs, including its newest, Biomedical Data Science, which graduated its first student.
“Class of 2020, I applaud your passion, your dedication, and your commitment to hard work,” said Marta Filizola, PhD, in greeting the graduates. Dr. Filizola is Dean of the Graduate School of Biomedical Sciences and the Sharon & Frederick A. Klingenstein/Nathan G. Kase, MD Professor of Pharmacological Sciences, and Neuroscience.
Marta Filizola, PhD
“This has, of course, been an academic year with an unusual conclusion. But even in these times, there is much to be grateful for. In a year when the world is filled with uncertainty, I also feel hope because of all of you,” she continued. “You have seen your studies through, and now, when they are greatly needed, you will be applying your new skills in biomedical sciences, in data science and statistics, in genetic counseling and clinical research, in public health and health care leadership, to meet some of the greatest challenges these fields have ever faced. Whether you continue in academia; pursue careers in biotechnology, pharmaceuticals, or other industries; or even start your own companies and show the world what it has been missing, I hope you will do it with drive, with discipline, with integrity, and with empathy. The world can use your help.”
Presiding over the ceremony was Eric J. Nestler, MD, PhD, Director of The Friedman Brain Institute, Dean for Academic and Scientific Affairs, and Nash Family Professor of Neuroscience. In addressing the graduates, he said: “We were caught flat-footed by COVID-19 and should have responded much better early on, but public health and modern medicine have saved the lives of innumerable people—through medical support, antiviral agents, and mitigation efforts—who otherwise would have died. And how impressive and heartening it has been to see the leadership role played by Mount Sinai and our health care heroes on the front lines in these efforts.”
Eric J. Nestler, MD, PhD
Still, Dr. Nestler cautioned, “As we continue to focus on containment and treatment, we must also now heed warnings on the impact of contagion on our humanity. We have already seen a dramatic increase in depression, post-traumatic stress, suicide, and drug overdoses, and we all expect that this is the tip of the iceberg of people who are hurting emotionally from the stress and fear of themselves or loved ones getting sick, in addition to the toll of social isolation and severe unemployment. We should also keep the toll of COVID-19 in perspective. Before the pandemic, 70,000 Americans died each year of drug overdoses, and 50,000 from suicides; one might argue that addiction, depression, and suicide have been pandemics for years to which our society has not paid nearly enough attention.”
Dr. Nestler introduced Helena Hansen, MD, PhD, Associate Professor of Anthropology and Psychiatry at the Grossman School of Medicine at New York University, who gave the Commencement address. Dr. Hansen also was awarded an honorary Doctor of Science degree for dedicating her “wide-ranging career to studying the intersections of social forces and medicine, identifying opportunities for improving health, and greatly improving access to care for all.”
Helena Hansen, MD, PhD
Dr. Hansen, who began her training at the peak of AIDS activism, challenged the graduates to seek wisdom in new places. “Our turbulent times have placed health inequalities and climate as centerpieces of social justice, at the very center of our society’s future. You, as highly trained scholars and practitioners of public health, are in the eye of the storm,” she said, as she provided the graduates with three principles for positive action. “Look for expertise and leadership from ‘below.’ The power structure of our society will continually belittle the knowledge of those who never had access to college or graduate education. Your job is to go against the grain and redefine knowledge, expertise, and power.”
She continued: “Look up to larger systems for fundamental causes of syndemics and health inequalities—their roots are almost always in policies and institutions. The predictable patterns of overlapping epidemics signal that they are biosocial in nature, that they represent the biological end points of social environmental assaults. Your job will be to continually redefine health problems from problems of individual behaviors to problems of pathological systems. Build communities of practice wherever you go: you will need the affirmation and power of many like-minded people.” Dr. Hansen concluded, “I congratulate you on choosing the eye of the storm for your career, and I look forward to meeting you there.”
Charles Sanky, MPH
Charles Sanky, a dual MD/MPH degree candidate who received a Master of Public Health degree and intends to complete his MD degree in 2021, was the student speaker. “I’d like to talk about muting ourselves,” he began. “It’s something we tend to do out of courtesy on Zoom calls, but we do this in real life, too—stopping ourselves from speaking our truth, taking action, and sharing what we have to offer. Some of us have felt powerless and incapable of meaningfully effecting change without more education, more skills, more experience. ‘If only I get my master’s, then I’ll be able to tackle the big questions. Then, I’ll be able to contribute. Then, I will be heard.’ We muted ourselves instead of realizing that we had a powerful voice all along.”
Mr. Sanky urged the Class of 2020 to not be silent. “Our graduation, this moment, celebrates our ability to raise our voices, to continue in that fight for serving humanity through health care,” he said. “We have the privilege, ability, and the duty to do something more, to push boundaries to reimagine solutions. In this moment, let’s promise ourselves that we will speak up, take action, be creative, and think beyond the structures handed to us. Class of 2020, let’s live our lives off mute.”
“Mount Sinai has been the perfect academic community for me for the past two years, growing my love of research while at the same time challenging me and developing my skills. I’m excited to keep chasing my aspirations as I continue on to complete my PhD at Mount Sinai and further my research goals.” —Kimberly Okoli, MSCR
“I’m the first one in my family to attain my master’s; therefore, while this is an academic achievement, it also feels like a hugely personal one. In retrospect, Mount Sinai provided the perfect environment and opportunity for me to pursue my graduate education. The rigor and wisdom of the professors really helped spark the curiosity and interest to learn. And, while my last semester here wasn’t exactly as I envisioned (due to COVID-19), Mount Sinai adapted really well and still opened new doors for me and my future.” —Aaron Sunil, MSCR
“The Master of Science in Clinical Research Program at the Icahn School of Medicine at Mount Sinai has the most comprehensive curriculum and exceptional faculty from a diverse clinical background, which provided me with the perfect intellectual and social milieu to extend my research skills and actively participate in this field. The knowledge and the experience I gained here will help me to pursue a career as a clinical researcher in the field of neurology.” —Dhaivat Shah, MBBS, MSCR
“My time in the Master of Public Health program gave me the opportunity to discover passions for health disparities research, environmental health, and preventive medicine that I never knew existed. Before coming here, I didn’t know that being a physician and research scientist was possible to balance. Having physicians as professors, and forming bonds with these mentors and becoming a part of their research endeavors created a very unique experience that I’m truly thankful for.” —Acacia Smash, MPH
“Upon graduating the Health Care Delivery Leadership Master’s program, I find both the world and myself transformed. The knowledge and expertise that I gained from the program have been invaluable in successfully leading my clinic through the pandemic. Armed with a renewed sense of determination and skills, I’m taking this opportunity to expand into various areas by both building on the clinic redesign I have started and taking the Addiction Medicine boards this fall.” — Jameela Yusuff, MD, MPH, Medical Director and Associate Professor of Medicine (Infectious Diseases), STAR Program, SUNY Downstate Medical Center