Research | Mount Sinai Today

Thousands of Mothers Take Part in Mount Sinai Study of COVID-19 and Pregnancy

May 6, 2021 | BFWHRI, COVID-19, Featured, OB/GYN, Pregnancy, Research

Jill Schechter, with baby Jonah, says she was grateful to participate in the study of COVID-19 and pregnancy.

A multidisciplinary team at Mount Sinai is conducting the first large-scale prospective study to examine the impact of COVID-19 infection during pregnancy on maternal and child outcomes. The study is funded by a $1.8 million contract from the Centers for Disease Control and Prevention (CDC) and is expected to be conducted through May 2022. The team calls it “Generation C” because it is studying the maternal experience during the COVID-19 pandemic.

“Early in the pandemic, there were reports that women who tested positive during delivery might have a higher risk of birth complications,” says a co-investigator, Veerle Bergink, MD, PhD, Professor of Psychiatry, and Obstetrics, Gynecology and Reproductive Science, Icahn School of Medicine at Mount Sinai. “We want to know, not only for symptomatic women but also for the asymptomatic women, what exposure to COVID-19 means for your obstetric outcomes and for your baby.”

The research team intends to recruit a cohort of 3,000 pregnant patients at The Mount Sinai Hospital and Mount Sinai West, with more than 2,500 enrolled to date.

One participant in the study is also a co-investigator—Whitney Lieb, MD, MPH, MS, Assistant Professor of Obstetrics, Gynecology and Reproductive Science, Population Health Science and Policy, and Medical Education, Icahn Mount Sinai. “There is limited data about how COVID-19 affects moms and babies, and I think it is important to get as much data as possible,” says Dr. Lieb, who gave birth at Mount Sinai West in July 2020. “That is why I decided to join the study.”

Whitney Lieb, MD, with baby Jacob, is both a participant and a co-investigator in the study. “There is limited data about how COVID-19 affects moms and babies,” says Dr. Lieb, Assistant Professor of Obstetrics, Gynecology and Reproductive Science, Icahn School of Medicine at Mount Sinai.

Jill Schechter, who gave birth on Valentine’s Day at The Mount Sinai Hospital, joined for the same reason. Ms. Schechter was vaccinated for COVID-19 while pregnant and asked her physician if there were any studies she could participate in. “I work in health care, and I am aware of the importance of research,” Ms. Schechter says. “I’m grateful for being able to participate.”

In the study, researchers are examining plasma samples drawn as part of routine care at each trimester of pregnancy in all pregnant women at the two hospitals. Samples are tested for the immunoglobulin M and immunoglobulin G antibodies to SARS-CoV-2, the virus that causes COVID-19, at each trimester of pregnancy and delivery. The team is measuring a panel of inflammatory biomarkers at each trimester of pregnancy and at delivery. The hypothesis is that the level of inflammatory host response to SARS-CoV-2 exposure is related to the impact of the infection on maternal and child outcomes, and that timing is crucial.

The study is examining the subjects’ electronic medical records, obtaining data on obstetric complications, miscarriage, premature rupture of membranes, delivery type, maternal ICU admissions, acute respiratory distress syndrome, sepsis, and maternal death. In addition, the team is extracting data on fetal growth and neonatal outcomes, including birth weight, preterm birth, neonatal morbidities, neonatal intensive care admissions, congenital malformations, and fetal and neonatal death.

“We are looking at the impact and timing of SARS-CoV-2 infection and the development of COVID-19 on these acute and severe complications,” says co-principal investigator Joanne Stone, MD, Director of the Division of Maternal Fetal Medicine, Mount Sinai Health System, and Professor of Obstetrics, Gynecology and Reproductive Science. “The aim is to investigate whether SARS-CoV-2 infection and a strong inflammatory host response are related to preterm delivery and neonatal morbidity.”

Another aim of the study is to examine the extent to which COVID-19 disproportionately impacts pregnant women from underserved communities. This part of the study is taking full advantage of the diversity of Mount Sinai’s patient population. “We have women from the affluent Upper East Side of Manhattan, from the Bronx, from Harlem,” says co-principal investigator Siobhan Dolan, MD, MPH, Vice Chair for Research and Director of Genetics and Genomics, Department of Obstetrics, Gynecology and Reproductive Science, and Co-Director of the Blavatnik Family Women’s Health Research Center. “The ethnic and socioeconomic diversity of our patients means that we do a very good job of reflecting the United States population.”

The World Health Organization classifies pregnant women as at high risk for serious COVID-19-related morbidity and mortality. The Mount Sinai study was proposed in response to a CDC call for research that will bolster the very limited data now available on the effects of SARS-CoV-2. It was designed by Dr. Bergink and Elizabeth Howell, MD, MPP, who is now Chair of Obstetrics and Gynecology at the Perelman School of Medicine at the University of Pennsylvania.

“This virus will be among us for a while,” Dr. Bergink says, “and it is good to have real-life data on the effects of COVID-19, especially in vulnerable groups, like pregnant women and high-risk populations.”

Mount Sinai Creates First Experimental Personalized Vaccine for a Variety of Cancers

May 3, 2021 | Featured, Research

The image of this Phase 1 trial shows the progress of one patient who began to mount a robust immune response to their cancer six months after receiving the full 10 dose-regimen of Mount Sinai’s experimental cancer vaccine. (T cells are represented by black dots, as seen in the bottom row.)

The first personalized cancer vaccine administered to patients prior to evidence of spread but after surgery or a stem cell transplant, was shown to be safe, well tolerated, and potentially beneficial in preventing disease recurrence in a phase 1 clinical trial at The Tisch Cancer Institute of the Mount Sinai Health System.

The results of the trial were presented virtually, in April, at the American Association for Cancer Research (AACR) Annual Meeting and generated excitement among attendees. It was the first time a personalized vaccine of this sort had been given to patients with a variety of cancers—including lung, breast, ovarian, and head and neck cancers as well as multiple myeloma, a disease of the white blood cells. Prior to receiving the vaccine, the patients either had surgery or an autologous stem cell transplant as a standard-of-care treatment. After an average follow-up of 880 days, 4 of the 13 patients in the trial had no evidence of disease.

Thomas Marron, MD, PhD

“Most of the patients in our study had well over a 50 percent chance of the cancer coming back,” says trial co-leader Thomas Marron, MD, PhD, Assistant Professor of Medicine (Hematology and Medical Oncology), and Director of The Tisch Cancer Institute’s Early Phase Trial Unit. “The No. 1 thing we were interested in was, did we successfully teach the patient’s T cells, their immune cells, what to look out for and what to kill in case there were microscopic pieces of the tumors that remained in the body? Hopefully, if the patient does have residual disease, those T cells can hunt it down and kill it.”

Immunotherapies are usually given after the patient’s cancer has already metastasized or spread to other parts of the body. But Mount Sinai administered its personalized vaccine before there was evidence of spread, so the vaccine could teach the body’s immune cells what to be on the lookout for in case remaining tumor cells were still circulating after surgery or stem cell transplant.

Another unique aspect of the trial was that each patient’s genetic information, including their normal DNA as well as their tumor’s DNA and RNA, were sequenced and run through OpenVax, Mount Sinai’s proprietary, computer program.

OpenVax compared the genetic information from the patient and the tumor to define which mutations, or changes, were unique to the tumor, and then identified 10 “foreign” proteins in each patient’s tumor that the patient would most likely develop an immune response to. A personalized vaccine for each patient was then created from synthetic versions of each of those 10 proteins in Mount Sinai’s Vaccine and Cell Therapy Laboratory, a highly specialized unit that meets the manufacturing standards of the U.S. Food and Drug Administration. The laboratory is run by the trial’s senior leader, Nina Bhardwaj, MD, PhD, Ward-Coleman Chair in Cancer Research, and Director of Immunotherapy at Icahn Mount Sinai.

Since the cost of developing each of these personalized vaccines is extremely high, it is unlikely that there will be a phase 2 of this particular trial, according to Dr. Marron. The goal of the trial “really is about informing future novel therapies,” he says. “Ideally, we will be able to get to the point where we do a biopsy and send it off to a lab and receive a vaccine, but that is very difficult to do now and very expensive. As the technology improves it may become possible.”

Nina Bhardwaj, MD, PhD

During their next phase of research, the Mount Sinai team plans to develop vaccines that can be administered to groups of patients who have the same cancerous mutations, instead of focusing on each patient’s unique DNA.

This research is being informed by Dr. Bhardwaj, who was the senior author of a paper in the December 10, 2020, issue of the journal Cell, which found that similar mutations appeared in a subset of patients with stomach, colon, and endometrial cancers.

“I’m looking forward to creating what we call ‘shared neoantigen vaccines,’” Dr. Marron adds. “This is based on our understanding that certain mutations exist in a high percentage of lung cancers, pancreatic cancers, colon cancers, and other types of cancer. If we were able to make a vaccine that covers, say, 100 different mutations, we would have a vaccine that could help a majority of cancer patients in the world.”

Currently, Dr. Marron and other top researchers at Mount Sinai are making inroads in an area of cancer vaccine development called in situ or “at the site of” vaccines, with at least eight early trials now under way. These vaccines are being administered to patients whose cancerous tumors have metastasized following their first round of standard-of-care treatment, such as surgery, chemotherapy, or radiation. Patients receive an injection directly into one of their tumors of an adjuvant that revs up the immune system, which instructs the immune system to find and kill other pieces of the tumor that may remain in the body.

Mount Sinai Recognizes Lab Team for their Work during the COVID-19 Pandemic

Updated on Jun 30, 2022 | Community, Research

COVID-19 brought numerous challenges for the hundreds of employees working in and with our medical laboratories across Mount Sinai Health System. They continued to show agility and dedication in meeting the changing needs of our community as the pandemic progressed. Mount Sinai wishes to recognize the contributions of these teams during Medical Laboratory Professionals Week, observed the last full week in April each year.

Mount Sinai lab colleagues have been involved with major breakthroughs over the past year because testing was central to learning about the COVID-19 pandemic.

At the start of the pandemic, our lab teams rapidly transformed their operations to expand and modify testing for COVID-19 as the number of patients affected grew and the standards for testing morphed. They quickly became a national leader in providing antibody testing and treatment, receiving Emergency Use Authorization for a very early version of the test which identified candidates for antibody plasma donation in early treatments.

Many studies about COVID-19 antibody responses in our patients were possible because of the coordination and hard work of the lab teams across Mount Sinai. They were also integral to establishing the Mount Sinai COVID-19 PCR Saliva Testing program as a part of the New York State Excelsior Pass program.

The Mount Sinai lab team is made up of many different people working in coordination across the Health System, including histologists, lab technologists, quality experts, lab information technology experts, physicians, autopsy and morgue teams, managers, and many more. Their continued dedication and collaboration is vital to keeping our community safe and well.

Mount Sinai Makes Studying the Brain Exciting and Fun for Schoolchildren

Updated on Jun 30, 2022 | Community, Featured, Research

Michael B. Fernando, a MiNDS volunteer and PhD neuroscience graduate student, leads a sheep brain dissection and a comparative anatomy lesson for high school students during Brain Awareness Week.

Neuroscience graduate students, postdocs, faculty, and volunteers from The Friedman Brain Institute at Mount Sinai recently hosted a series of special activities during Brain Awareness Week, part of an annual global campaign each March by the Dana Foundation to increase public awareness on the progress and benefits of brain research.

Mount Sinai’s effort, which included fun classroom activities for elementary school children, lessons on comparative brain anatomy for high schoolers, podcasts, and a public lecture—all virtual—was driven by MiNDS, Mentoring in Neuroscience Discovery at Sinai. MiNDS is an educational initiative led by graduate students that makes neuroscience engaging and accessible for East Harlem, New York, schoolchildren. The Art of the Brain exhibit, typically held in an East Harlem, New York, art gallery, became a virtual sensation and remains open to the public until Friday, May 28.

“Our activities during Brain Awareness Week looked a little different this year without our onsite, interactive Brain Fair that would attract 500 visitors,” says Denise Croote, co-leader of MiNDS and a fifth-year PhD neuroscience graduate student, “but we were very excited that we were able to extend our enthusiasm about the brain into the virtual space.”

MiNDS partners with the Center for Excellence in Youth Education (CEYE) within the Office for Diversity and Inclusion —all part of a long and far-reaching effort of the Icahn School of Medicine at Mount Sinai. CEYE has been providing real-world classroom activities and interactions with faculty and staff since its founding in 1975, introducing summer and academic year internships and courses to thousands of underrepresented students interested in exploring careers in medicine, science, technology, and engineering.

Elementary school students learn brain basics during a Morning MiNDS program offered by PhD neuroscience graduate students Denise Croote and Brittany Hemmer.

They streamed four “Morning MiNDS” lessons at 9 am for elementary school students, covering the lobes and cells of the brain, and the sensory systems. “We also led students through several fun experiments using supplies we distributed in experiment bags,” Ms. Croote said. A cadre of MiNDS volunteers had assembled 500 bags, distributing 300 to students at its partner school, Patrick Henry Preparatory PS/IS 171, and the others to the Mount Sinai community, so they could participate in a hands-on activity remotely.

The other programs included:

Streaming a sheep brain dissection and a comparative anatomy lesson for high school students, and looking at the brains of mice, rats, dogs, bears, and humans.
Hosting a public lecture (with Spanish subtitles), “The Social Brain: Adapting During the COVID-19 Pandemic.” It included presentations on the neuroscience of social behavior and the impact of social distancing on mental health, and featured MiNDS co-leader Joseph Simon, IV, a fourth-year neuroscience PhD graduate student, and Anastasia Shuster, PhD, a postdoctoral fellow in the Department of Psychiatry.

Anastasia Shuster, PhD, a postdoctoral fellow in the Department of Psychiatry, co-hosted a public lecture that included Spanish subtitles on “The Social Brain: Adapting During the COVID-19 Pandemic.”

And, special this year: the launch of a podcast series, “Journey Through the MiND: Exploring the Life of a Neuroscientist.” The podcast series was sponsored by the Dana Foundation and featured revealing conversations with Friedman Brain Institute faculty. Topics included pivotal experiments that helped shape their careers, and the overall twists and turns of the research world. Ms. Croote talked to Daniela Schiller, PhD; and Mr. Simon chatted with Uraina Clark, PhD.

While Brain Awareness Week has concluded, the commitment to the community is ongoing in new and imaginative ways. Says Kenya Townsend, CEYE’s Program Director: “For months, we have been planning new programs, and this summer we will be offering two engaging programs for current New York City high school students: Introduction to Bioinformatics, and Medical and Scientific Exploration. We are excited about these programs and these new students who are eager to learn about science.”

Pregnancy and Antidepressants: Should You Avoid Taking Them?

Updated on Jun 30, 2022 | Featured, Mental Health, OB/GYN, Psychiatry, Research, Women's Health, Your Health

Approximately half of women who use antidepressants before pregnancy decide to discontinue use either before or during pregnancy due to concerns about the negative consequences for their child.

Those who are pregnant or who may be thinking of getting pregnant may wonder if taking antidepressants could affect the heath of the child. New research from Mount Sinai offers some potentially important findings and shows that the underlying mental health of the parents is more of a concern than the medication itself.

The study shows that while there is a link between maternal antidepressant use during pregnancy and affective disorders in the child later in life, the link also exists between paternal antidepressant use during pregnancy and child mental health.

The data suggest the observed link is most likely due to the underlying mental illness of the parents rather than any “intrauterine effect,” which means any effect the medication could have on the fetus developing inside the uterus. These affective disorders include depression and anxiety.

“Our study does not provide evidence for a causal relationship between in-utero exposure to antidepressants and affective disorders in the child,” says Anna-Sophie Rommel, PhD, an instructor in the Department of Psychiatry at Icahn Mount Sinai and first author of the paper. “So, while other long-term effects of intrauterine exposure to antidepressants remain to be investigated, our work supports antidepressant continuation for women who would like to continue taking their medication, for example because of severe symptoms or a high risk of relapse. It is important to note that untreated psychiatric illness during pregnancy can also have negative consequences on the health and development of the child. Women and their health care providers should carefully weigh all of the treatment options and jointly decide on the best course of action.”

Anna-Sophie Rommel, PhD

Approximately half of women who use antidepressants before pregnancy decide to discontinue use either before or during pregnancy due to concerns about the negative consequences for their child, according to Dr. Rommel, who is also an expert in epidemiology and has been studying how the COVID-19 pandemic disproportionately affects pregnant women in underserved communities.

Major depressive disorder is highly prevalent, with one in five people experiencing an episode at some point in their life, and is almost twice as common in women than in men. Antidepressants are usually given as a first-line treatment, including during pregnancy, either to prevent the recurrence of depression, or as acute treatment in newly depressed patients. Antidepressant use during pregnancy is widespread and since antidepressants cross the placenta and the blood-brain barrier, concern exists about potential long-term effects of intrauterine antidepressant exposure in the unborn child.

Using the Danish National Registers to follow more than 42,000 babies born during 1998-2011 for up to 18 years, researchers at the Icahn School of Medicine at Mount Sinai investigated whether exposure to antidepressants in the womb would increase the risk of developing affective disorder like depression and anxiety in the child.

In a study published April 5 in Neuropsychopharmacology, the scientists found that children whose mothers continued antidepressants during pregnancy had a higher risk of affective disorders than children whose mothers stopped taking antidepressants before pregnancy.

However, to understand whether the underlying disorder for which the antidepressant was given or the medication itself was linked to the child’s risk of developing an affective disorder, they also studied the effect of paternal antidepressant use during pregnancy and similarly, found that children of fathers who took antidepressants throughout pregnancy had a higher risk for affective disorders. Thus, the research team speculates that rather than being an intrauterine effect, the observed link is most likely due to the parental mental illness underlying the antidepressant use.

Students Present Their Latest Studies at Medical Student Research Day

Mar 30, 2021 | Featured, Research

One hundred six poster presentations and four oral presentations capped off new research that was conducted by students at the Icahn School of Medicine at Mount Sinai and featured at Mount Sinai’s Fourth Annual Karen Zier, PhD, Medical Student Research Day, held over Zoom in March.

Participating in Research Day fulfills one of the medical school’s graduation requirements. Eighty percent of the presenters each year are in their second year of medical school.

“Medical Student Research Day is a showcase and an opportunity for students to share the research and scholarship they have done with their mentors with the Mount Sinai community,” says Mary Rojas, PhD, Director of Icahn Mount Sinai’s Medical Student Research Office, and Associate Professor of Medical Education. “It is an early snapshot of the students’ accomplishments.”

Dr. Rojas says that by the time they graduate, more than half of Mount Sinai’s students will have published in peer-reviewed journals. The Class of 2021 has already published more than 400 peer-reviewed articles.

The event exemplifies Mount Sinai’s commitment to fostering biomedical research and introduces students to the intellectual rigors, skills, and collaboration that lead to incremental findings and life-changing discoveries.

Under the mentorship of Tanvir Choudhri, MD, Associate Professor of Neurosurgery, at Icahn Mount Sinai, second-year student Zachary Spiera found that the use of non-steroidal anti-inflammatories (NSAIDs), which diminish inflammation, does not make users more susceptible to concussions and does not worsen their outcomes. This was a subject he had wondered about because he and his teammates had plied themselves with NSAIDs while playing basketball and soccer in high school and middle school.

Before launching his own research, Mr. Spiera searched through medical literature, but could not find an answer. “As a student you look up to the medical community and think there are going to be answers to your questions,” he says. “Then you see something that hasn’t been figured out yet.” He is first author on a study about this subject that was recently accepted for publication in the Journal of Neurosurgery: Pediatrics.

This spring, Jordyn Feingold will receive a joint MD and Master of Science in Clinical Research, before continuing at Mount Sinai for her residency in Psychiatry. At Research Day, she presented her work on the psychological impact of the COVID-19 pandemic on 2,579 front-line health care workers at The Mount Sinai Hospital. She and her mentor, Jonathan Ripp, MD, MPH, Dean for Well-being and Resilience and Professor of Medicine (General Internal Medicine, and Geriatrics and Palliative Medicine) recently published their findings in the journal Chronic Stress.

One of the study’s key takeaways, Ms. Feingold says, was the high prevalence—39 percent—of COVID-19-related post-traumatic stress disorder, major depressive disorder, or generalized anxiety disorder that existed among the hospital’s front-line health care workers at the peak of the pandemic last year. The “greatest driver of those symptoms was being burned out, which is significant,” she says, “because it was happening well before COVID-19 and it is something that can be addressed.” Her research also found “the greatest modifiable protective factor was feeling supported by hospital leadership.”

The COVID-19 pandemic provided a springboard for student research by others, including second-year students Cynthia Luo, Alexander Kalicki, and Kate Moody, who also presented abstracts of their studies on Research Day.

Ms. Luo studied resilience among her fellow medical students during the pandemic under the mentorship of Craig Katz, MD, Clinical Professor of Psychiatry, Global Health, and Medical Education, at Icahn Mount Sinai. She divided students into two groups: those who responded to a survey by saying the COVID-19 pandemic had been their most traumatic life event, and those who responded by saying they had experienced earlier life traumas, such as the loss or illness of a loved one. Ms. Luo then measured their responses on a resilience scale that was created at Mount Sinai. “Students who indicated a non-COVID-19 impactful life event had significantly higher resilience than those who indicated COVID-19,” says Ms. Luo. “To me that demonstrates that having prior stressful life experiences was, in some ways, protective for managing COVID stress. Potentially, these experiences helped students grow and develop their resilience behaviors before COVID-19.” Ms. Luo plans to finish compiling her research and submitting it for publication in the coming months.

Mr. Kalicki and Ms. Moody are co-authors on a study that was just accepted by the Journal of the American Geriatrics Society (JAGS), which examined the barriers to video-based telehealth access that older homebound adults faced during the pandemic. Mr. Kalicki worked as a software engineer before entering medical school and says his passion for using technology to improve health care delivery led him to pursue the project under the mentorship of Peter Gliatto, MD, Professor of Medicine (General Internal Medicine), Geriatrics and Palliative Medicine, and Medical Education at Icahn Mount Sinai. Katherine Ornstein, PhD, MPH, Associate Professor, Geriatrics and Palliative Medicine, also served as the students’ mentor.

Ms. Moody says she was drawn to the subjects of process improvement and providing a high level of health care to a population that is difficult to access. Both students helped design a survey that was completed by physicians in the Mount Sinai Visiting Doctors Program and conducted the data analysis for the study. They also created a data collection sheet for Mount Sinai’s Epic electronic health record system to systematically record information about patients’ previous telehealth use, as well as structural barriers patients may face, such as access to the internet or the capacity to pay for cellular data. The students hope that a better understanding of these barriers will help inform future interventions that are designed to reach patients with limited access to care.