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

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.”

 

Athlete Finds a Team to Help Her Beat Multiple Sclerosis

“Ten years ago I thought my life was over. I did not think I could find the right partner or even have children. Being a part of the Corinne Goldsmith Dickinson Center for Multiple Sclerosis at Mount Sinai has helped me and my family so much.” — Jessica March

In 2009, when Jessica March was 29 years old, she began experiencing tingling in her toes and blurry vision.  She was an athlete, and thought she was training too much for a 100-mile bike ride.

“You find all these excuses,” she said. “I remember waking up one morning, I opened my eyes, and I was completely paralyzed.”  Mrs. March was terrified.  “I felt like my body was in a straitjacket,” she said.  She panicked and was screaming while pulling herself along the ground.  “I didn’t know what was wrong with me, I was crying for days,” she said.

The first doctor she saw was a general neurologist who told her she had fibromyalgia.  However, when she got her test results from the hospital, she started doing her own research and suspected multiple sclerosis (MS), a condition she had never heard of prior.

Jessica found a specialist for multiple sclerosis who started treating her for MS. This specialist referred her to Stephen Krieger, MD, Professor of Neurology, at the Corinne Goldsmith Dickinson Center for Multiple Sclerosis at Mount Sinai.  “It’s been over 10 years, and I have never looked back,” she said.

Her diagnosis and treatment started with an MRI and medications.  But with Dr. Krieger and the Corinne Goldsmith Dickinson Center, her treatment also emphasized the overall wellness of her life and how to thrive while living with this condition.

“He introduced me to the MS support group, and I was exposed to studies and data showing that people with MS can thrive,” Mrs. March said.  In addition to her medications, her treatment includes nutrition, exercise, stress management, and mental health.

“Working with this team, I feel more confident talking to others and helping them,” she said. “I started in this dark place. Ten years ago I thought my life was over.  I did not think I could find the right partner or even have children.  Being a part of the MS Center has helped me and my family so much.” She is married and has two children.

Why should patients with multiple sclerosis choose Mount Sinai?  “This faculty is the best in the world for researching and treating MS,” said Mrs. March, who credits Dr. Krieger, clinical neuropsychologist James Sumowski, PhD, and Ilana Katz-Sand, MD, along with the nurses and fellows, and the entire office staff at the Corinne Goldsmith Dickinson Center for Multiple Sclerosis at Mount Sinai.

“Their life mission is to support patients and caregivers,” she says. “It’s not just about a prescription on a prescription pad, it’s about your whole life. This group really cares.”

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

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.

Compassion and Connection: Caring for Patients in a Time of Need


Patient Experience Week, observed Monday, April 26, through Friday, April 30, honors the people who improve the patient experience every day and celebrates their accomplishments.

From nurses and physicians to support staff and executive professionals, all Mount Sinai employees are part of the patient experience.

This year Mount Sinai is recognizing how employees connected with patients through compassion during COVID-19. In this video, you can see how in many different ways, teams across many Mount Sinai locations—both clinical and non-clinical, remote and in-person—rose to the occasion, moved past barriers, showed compassion, and innovated to effectively care for patients in a time of need.

Watch Mount Sinai Brooklyn

Watch Mount Sinai West

Watch Mount Sinai Beth Israel

Watch NYEE

Watch Mount Sinai Queens

Mount Sinai Doctors

Mount Sinai South Nassau

Mount Sinai Morningside

The Mount Sinai Hospital

Watch the slideshow of employees throughout the Mount Sinai Health System

 

Pregnancy and Antidepressants: Should You Avoid Taking Them?

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.

Saving Baby Nathaniel: As the Nation Went Into Lockdown Mount Sinai’s Liver Transplant Team Went Into Overdrive

Image of jaundiced 6-month-old Nathaniel in hospital prior to transplant

Prior to his transplant surgery, Nathaniel Capelo was severely jaundiced. He required continuous blood transfusions and his belly had to be drained of fluid every other day.

On March 18, 2020, the anguished parents of 6-month-old Nathaniel Capelo sat in his hospital room at The Mount Sinai Hospital facing the grim reality that he would die within days if he did not receive a new liver. One week earlier, the COVID-19 pandemic had begun to grip the nation and widespread lockdowns were taking place. But at 10:30 that night, the couple received a phone call from Mount Sinai’s transplant team that offered tiny Nathaniel a potential lifeline: the family of a shooting victim in his early 20s, who had just died in another state, were willing to donate his liver—epitomizing the “good news/bad news” world of organ transplants.

At the time, operating rooms throughout New York City were being converted into intensive care units to house severely ill patients with COVID-19 who were beginning to strain the city’s health care system, and many hospitals had started suspending their transplant procedures altogether. The hospital where the donor had died told Mount Sinai’s Recanati/Miller Transplantation Institute that its surgeon Chiara Rocha, MD, and her team would have to bring their own personal protective equipment to wear while extracting and retrieving the donated liver to bring back to New York. Charter airline companies were shutting down flights and Mount Sinai’s administrators worked their magic in securing a Learjet to fly Dr. Rocha and her team hundreds of miles to and from the donor hospital in the middle of the night.

“The stars lined up,” says Sander S. Florman, MD, Director of the Recanati/Miller Transplantation Institute. “This was as logistically complicated as anything we have ever done and in a child where everything was stacked against him.”

To this day, Nathaniel’s doctors do not know what caused his rapid liver failure. But now, the inquisitive 20-month-old toddler “is going to do great,” says Dr. Florman. Three-quarters of the liver he received was transplanted into an adult patient at Mount Sinai, who is also doing well.

Members of Mount Sinai’s Liver Transplant team include, from left: Antonios Arvelakis, MD, Associate Professor of Surgery; Marcelo E. Facciuto, MD; Sander S. Florman, MD; and Chiara Rocha, MD.

The liver is the only organ in the body that can regenerate and grow. “But what most people don’t know is that if the liver is too big for the body it can shrink down,” says Dr. Florman. This is significant because at the time of his transplant surgery Nathaniel weighed only 11 pounds, representing “the extreme technical complexity” of what was possible, he adds.

Most children requiring a transplant would receive 20 percent of an adult liver—a size much too large for Nathaniel. Before the transplant could take place, Marcelo E. Facciuto, MD, Professor of Surgery at the Icahn School of Medicine at Mount Sinai, had to cut the donor liver down to the “smallest anatomic segment” possible, says Dr. Florman. But even that was too big. Following the seven-hour surgery led by Dr. Florman, the team left Nathaniel’s abdomen open for four days in order to shrink the liver to a size that was able to fit inside his tiny body.

After conducting more than 4,500 transplants during its 32-year history, Mount Sinai’s program has encountered a challenging surgery like Nathaniel’s only a dozen or so times, says Dr. Florman. “You’re talking about sewing an artery that’s just a couple of millimeters with sutures that are as fine as your hair. You are connecting the artery, the veins, and the bile duct, and it is all done with what we call a loop—glasses with a built-in microscope lens because it’s too small to complete with just your eyes.”

He adds, “Transplant is the epitome of a team sport and you can’t do this without having a tremendous team or without an institution that has unbelievable depth. Only a small number of transplant centers in the country would have been willing to take on a child this small. Even in the best of times this would have been a great triumph and a great case. This was even more so considering the time in which it happened.”

In fact, March 2020 marked the busiest month ever for Mount Sinai’s liver transplant program, which conducted 23 transplants, some of which were referrals from other programs that had just shut their doors.

Image of health 20-month-old Nathaniel among his toys

Today, at 20-months of age, Nathaniel is on track to hit all of his milestones. He is walking on his own, beginning to talk, and able to eat tiny pieces of solid food.

Nathaniel recently celebrated the one-year anniversary of his life-saving surgery, and his prognosis is good. Each month that goes by lowers the chances that his body will reject his transplanted liver. He has been weaned off of all but one of his 13 medications.

“Dr. Florman and his team were just amazing,” says Nathaniel’s father, Dennis Capelo. He and Nathaniel’s mother, Alexandra Ramos, remained at the hospital with their child during the five-month ordeal. Nothing could have prepared them for “the scariest time we ever had to deal with,” says Mr. Capelo, who has a 3-year-old son and 10-year-old daughter from a prior relationship.

He says, “We try to cherish every moment we have. We spend as much time as possible with all of the kids and each other and hope for the best.” He and Ms. Ramos have remained close to Nathaniel’s former Mount Sinai nurses and send them photos and videos to mark their toddler’s milestones, including his first steps. “They became like family to us,” Mr. Capelo says.

One of Nathaniel’s physicians, Ronen Arnon, MD, Professor of Pediatrics, Hepatology, and Liver Transplantation at the Icahn School of Medicine at Mount Sinai, remembers how “Nathaniel struggled to survive. The first months of his life were spent in a hospital bed rather than at home, and his first friends were his doctors and nurses. He suffered from eating and breathing difficulties and he could barely move due to his swollen abdomen.”

Another of his physicians was John Bucuvalas, MD, Chief of Pediatric Hepatology, Professor of Pediatrics, and Director of Solid Organ Transplant Outreach, Jack and Lucy Clark Department of Pediatrics, and Mount Sinai Kravis Children’s Hospital. “Today, Nathaniel is an active toddler and exploring his world. He won’t remember the transplant,” Dr. Bucuvalas says. “But for his parents, the Intensive Care Unit, P5 (Pediatric floor 5) teams, and the liver team, the series of events are etched in our memory and remind us of why we do what we do.”

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