Research | Mount Sinai Today

COVID-19 Research Roundtable

May 12, 2021 | BFWHRI, Research

Almost exactly one year ago, New York City faced the outbreak and first peak of the pandemic, and the city accounted for 25 percent of COVID-19 deaths in the United States. Mount Sinai Health System and health care workers responded to an unprecedented surge of COVID-19 patients, and researchers and scientists immediately shifted gears to support discovery and innovation in improving prevention, treatment, and equity in this disease.

The Blavatnik Family Women’s Health Research Institute similarly began to focus on how the pandemic has affected women’s health, on both the side of the patient and the health care provider. And on April 12, 2021, on the one-year anniversary of the peak, the Institute’s faculty members shared their research findings thus far.

Moderated by the Institute’s Associate Director Teresa Janevic, MD, MPH, the COVID-19 Research Roundtable provided members of the Institute space to share their ongoing work. The event comprised two sections: The Women’s Health Worker, and The Women’s Health Patient.

Caitlin Carr, MD

The Women’s Health Worker panel included Caitlin Carr, MD, a fellow in the Gynecological Oncology program, who discussed her study that focused on mental health among gynecological oncology providers during the pandemic, research that she also presented at the SGO 2021 Virtual Annual Meeting on Women’s Cancers. Her key findings in the gynecological oncology workforce helps to demonstrate that health care worker well-being and mental health during the pandemic is extremely relevant and provides key insight into the improvements and reforms that may be required in a hospital system.

Nina Molenaar, MD, PhD

In the Women’s Health Patient panel, Nina Molenaar, MD, PhD, began by outlining her work in the Generation-C study, which measures perinatal outcomes for women who have COVID-19 while pregnant. Current literature demonstrates that SARS-CoV-2 infection during pregnancy is associated with, among other things, increased risk of preterm birth and C-Section.

The Generation-C study uses serological tests to measure IgG antibody levels of pregnant women receiving obstetrical care in the Mount Sinai Health System and aims to analyze the correlation between seropositivity and pregnancy outcomes such as preterm birth, small or large for gestational age, NICU admission, and APGAR score. This ongoing prospective cohort study is expanding our understanding of the effects of COVID-19 infection during pregnancy.

Sheela Maru, MD, MPH

Next, Sheela Maru, MD, MPH, shared her findings within the CoronaVirus Impact on Birth Equity (VIBE) Study, which examines the birth experiences and discrimination that birthing people have felt during the COVID-19 pandemic, and how those experiences and exposures may have had an impact on postpartum health.

This study, which uses a cross-sectional web-based survey, examines patients across Mount Sinai Hospital and Mount Sinai West, Elmhurst Hospital Center and Queens Hospital Center, to understand the satisfaction of women who gave birth during the peak of the pandemic, and how this may differ across race and ethnicity. The VIBE study provides opportunities for interventions to address racism, improve birth satisfaction, and promote positive postpartum health outcomes.

The final presentation of the roundtable was led by Kimberly Glazer, PhD, MPH, who discussed the BFWHRI COVID-19 Perinatal Quality Database, an ongoing effort by the Department of Obstetrics and Gynecology in collaboration with the Institute to streamline the process of using Electronic Medical Record (EMR) data for in-depth monitoring and evaluation of obstetric quality during the pandemic.

Kimberly Glazer, PhD, MPH

Dr. Glazer discussed how this database of electronic medical records, while designed to produce internal quality reports, also serves as a tool to improve the performance of EMR data in reporting and research. The utility of this approach was demonstrated in the recent Jama Network Open article by Glazer, Janevic, and other BFWHRI faculty members, which used electronic medical records obtained from two hospitals in New York City to determine if racial/ethnic disparities in very preterm birth (VPTB) and preterm birth (PTB) increased during the first wave of the COVID-19 pandemic in New York City.

The Research Roundtable was a success, drawing on an audience across the Department of Obstetrics and Gynecology, Department of Population Health Science and Policy, and Blavatnik Family Women’s Health Research Institute members. The roundtable was not only a demonstration of the abundance of academic knowledge that Institute researchers have worked to discover, in just a little over a year, about COVID-19 and its impacts, but also an illustration of our scientists, clinicians, and researchers’ abilities to persevere.

During the peak of the pandemic in New York City, the core research team within the Institute continued to meet virtually to discuss various research projects, and quickly mobilized to produce meaningful research investigating the pandemic and its effects on women’s health. BFWHRI researchers have exhibited tremendous productivity and resiliency while navigating work-from-home orders and remaining healthy and safe during these unprecedented times.

The known gender gap in academia means that female academics, particularly those who have children, which represents the vast majority of the Institute’s faculty, report a disproportionate reduction in time dedicated to research relative to what comparable men and women without children experience. And so the COVID-19 Research Roundtable was not only a time to share outstanding research findings and discuss key next steps, but also served as a brief moment of reflection, to appreciate the efforts and challenges overcome thus far, and celebrate a team of outstanding women who have been committed to maternal and infant health equity research throughout the pandemic.

Mahima Krishnamoorthi, BA, is the Clinical Research Coordinator at the Blavatnik Family Women’s Health Research Institute, where she develops and fosters her passion for maternal and infant health equity and reproductive justice. She will be attending Johns Hopkins School of Medicine beginning in August 2021.

Scientists Celebrate International Day of Immunology and Their Role in Advancing Breakthroughs for COVID-19

May 6, 2021 | COVID-19, Featured, Research

Renowned immunologist Miriam Merad, MD, PhD, center, and members of Mount Sinai’s Precision Immunology Institute created T-shirts that support COVID-19 vaccinations in honor of International Day of Immunology.

The significant role the human immune system has played in the spread and containment of the SARS-CoV-2 virus, which causes COVID-19, was the subject of an International Day of Immunology summit, held virtually on Thursday, April 29, 2021, and co-organized by pioneering immunologist Miriam Merad, MD, PhD, Director of the Precision Immunology Institute at the Icahn School of Medicine at Mount Sinai. Dr. Merad, who, in 2020, was elected to the National Academy of Sciences, also serves as Director of Mount Sinai’s Human Immune Monitoring Center.

Scores of prominent researchers from throughout the world gathered at the summit to celebrate the international collaboration that took place during the pandemic and the speed at which their work was translated into desperately needed treatments. Their deep understanding of the different ways in which the human immune system reacts to SARS-CoV-2 has helped guide the worldwide medical response.

Anthony S. Fauci, MD, Director of the National Institute of Allergy and Infectious Diseases, gave opening remarks. “As an immunologist, physician, and U.S. government official, who, for decades, has helped lead the public health response to emerging diseases, it has become clear to me the important role that immunology plays in medicine and in infectious diseases,” he told the audience.

“People with healthy, intact immune systems—such as most young people—can control SARS-CoV-2 infection by limiting its effects to the upper airways in mild symptoms,” Dr. Fauci said. “In contrast, older people or individuals whose immunity is compromised by immunosuppressive agents, or an immune-compromising illness such as cancer, are unlikely to produce a robust immune response that can keep SARS-CoV-2 in check. When the history of this COVID-19 pandemic is written, the discipline of immunology will stand out for its important role in explaining the remarkable protean manifestations of SARS-CoV-2 infection and in enabling us to identify and exploit vulnerabilities in the virus to develop safe and effective vaccines to thwart its pandemic spread.”

Florian Krammer, PhD

The summit’s participants also included Özlem Türecki, MD, Co-founder and Chief Medical Officer of BioNTech, the company that partnered with Pfizer to produce the first authorized mRNA vaccine and the first vaccine to fight COVID-19; and Florian Krammer, PhD, Mount Sinai Professor in Vaccinology at the Icahn School of Medicine at Mount Sinai, who created one of the world’s first antibody tests for SARS-CoV-2.

Dr. Türecki described the development of BioNTech’s mRNA vaccine for COVID-19, which the company dubbed “project light speed,” beginning in January 2020 as soon as virus’ genetic sequence became known. She said BioNTech’s early investment in mRNA technology allowed the company to move quickly, particularly when their scientists expected the pandemic to spread “even faster” than it ultimately did.

BioNTech created 20 vaccine candidates at first, and then pared them down to four. By July, the company selected its “pivotal candidate” for phase 3 efficacy testing. In November, the vaccine was found to be 95 percent effective, and in December, the United States began administering the vaccine under the Food and Drug Administration’s Emergency Use Authorization.

According to Dr. Türecki, BioNTech was able to reach the market quickly by perfecting its manufacturing process at the same time it developed the vaccine. The Pfizer-BioNTech vaccine has now been authorized in more than 65 countries and administered to more than 260 million people.

Dr. Krammer said that eventually, scientists will “disentangle” the many questions that still remain about SARS-CoV-2 and the adaptive human immune system. For example, will people have long lasting immunity? He also questioned whether it would be advantageous to receive two different COVID-19 vaccines rather than the same one twice.

“But there’s a more pragmatic question here,” he said. “We are in a situation right now where we don’t have enough vaccines, and the production rate of the vaccines that are currently produced and licensed is not high enough to cover the globe and a lot of countries are struggling to get access to vaccines.” Improving the situation is critical.

Indeed, Ester C. Sabino, PhD, Professor, Institute of Tropical Medicine, at the University of São Paulo, Brazil, said, “If we don’t have access to vaccines, then probably herd immunity will never be reached.”

Panelist Adrian Hill, DPhil, Director of the Jenner Institute at Oxford University in England, and a co-developer of the AstraZeneca vaccine for COVID-19, concurred. “The biggest failing in responding to COVID-19 has not been in vaccine technology—they perform really well. And it hasn’t been in the speed of response—that’s been extraordinary,” he said. “It’s been in the lack of physical locations that manufacture vaccines widely around the world. We need to have facilities that can flip overnight to make outbreak pathogen vaccines.”

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.

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.