Research | Mount Sinai Today

Antibodies to COVID-19 in Human Breast Milk Being Tested as a Potential Therapy

May 22, 2020 | COVID-19, Featured, Research

Rebecca Powell, PhD, right, with lab technician Alisa Fox

Could the dominant antibodies found in milk produced by women who have recovered from COVID-19 serve as a potent treatment for individuals—both adults and children—who now have the disease? Rebecca L. Powell, PhD, Assistant Professor of Medicine (Infectious Diseases), at the Icahn School of Medicine at Mount Sinai, is pursuing research to answer that question. An HIV researcher, Dr. Powell has also studied human breast milk extensively for its significant role in human health.

In early April, Dr. Powell began a large recruitment effort in New York City, collecting breast milk from 1,600 lactating women, 600 of whom had recovered after testing positive for COVID-19, and others who may have had the disease but were never tested and still produced antibodies.

Dr. Powell tested the milk in a small percentage of women and uploaded the study to the preprint server medRxiv. She reported that 14 out of 15 donors also had a significant level of COVID-19-reactive antibodies in their milk, which was enough to warrant moving forward with further investigation on a larger scale.

“There are a lot of reasons to believe this is worth exploring,” Dr. Powell says. “Milk antibodies are enriched with secretory antibodies and unique from those found in blood. Antibodies that are very dominant in milk are meant to be in the mucosal areas of the body, like the respiratory tract, and they would function well and be durable in this environment.” Secretory antibodies found in the gut and lungs are highly resistant and provide the first line of defense against many pathogens.

Since the SARS-CoV-2 virus, which leads to COVID-19, often begins in the respiratory tract, this is precisely the environment in which such antibodies would need to function.

Dr. Powell says the secretory antibodies from human milk could serve as a potential treatment in the same way blood antibodies do in antibody therapy, where the antibody-rich plasma from patients who have recovered from COVID-19 is transferred into patients with the disease. The Mount Sinai Health System was one of the first health providers in the nation to use this therapy.

The study’s data, Dr. Powell wrote, represents a “snapshot of what is likely a dynamic immune response. A much larger sample size and long-term follow-up study is needed to better understand SARS-CoV-2 immunity in milk, as well as whether a typical response is truly protective for breast-fed babies or if this response would generate sufficient antibodies to be purified and used therapeutically to treat COVID-19 illness.”

If a larger study ultimately supports the hypothesis, Dr. Powell says she envisions a potential therapy for patients with mild and severe cases of disease that could be administered directly into an individual’s lungs, much like the nebulizers that are used for treating asthma. She also says there is significant value in understanding how these secretory antibodies confer protection to breast-fed babies and for establishing a baseline for the protection they provide after vaccines become available.

“Unlike blood, human milk can be given daily and the supply can be increased by pumping,” Dr. Powell says. “There are likely many women in New York City who would donate their milk every day if they knew it could save lives.”

New Institute for Health Equity Research Studies Issues Spotlighted by COVID-19

May 21, 2020 | COVID-19, Diversity and Inclusion, Featured, Public Health, Research

Co-Director Lynne Richardson, MD, left, and Director Carol Horowitz, MD, MPH, are guiding the new Institute for Health Equity Research. View an interview with Dr. Richardson on racial disparities and COVID-19.

The Mount Sinai Health System’s new Institute for Health Equity Research is quickly acting on its mandate to rigorously study disparities in health issues, including COVID-19, with the intention of translating those discoveries into initiatives and policies that benefit communities in New York and the nation.

“Our extensive expertise in population health and serving one of the most socioeconomically, demographically, and culturally varied populations in the world makes us uniquely positioned to take on this enormous challenge,” says Dennis S. Charney, MD, the Anne and Joel Ehrenkranz Dean of the Icahn School of Medicine at Mount Sinai, and President for Academic Affairs of the Mount Sinai Health System.

The COVID-19 pandemic is shining a light on long-existing health inequities, according to the Institute’s Director, Carol Horowitz, MD, MPH, Professor of Population Health Science and Policy, and Medicine, and Dean for Gender Equity in Science, and its Co-Director, Lynne D. Richardson, MD, Professor and Vice Chair of Emergency Medicine, and Professor of Population Health Science and Policy.

“Who gets COVID-19, who lives and who dies, maps very well, unfortunately, with other kinds of maps we have in New York City,” Dr. Horowitz says. “This includes areas of poverty, areas of majority of low-income, Latinx, and African American people, areas of more pollution, areas of more linguistic isolation, areas that have had more redlining in the past and other structural inequities. If you look at any map of New York City, and where people are marginalized, don’t have equal opportunities, and have higher burdens of chronic diseases, these are the same areas where COVID-19 seems to be hitting the most.”

Initiatives in Progress

The Institute has a variety of initiatives in progress, including Speak Up on COVID-19, a survey that was just launched in partnership with more than 100 New York City community organizations. “Speak Up” will be available in 11 languages to anyone with access to a smartphone. It is seeking to enroll more than 10,000 participants and will explore medical, demographic, social determinants, and COVID-19-related attitudinal, behavioral, and psychological factors; and try to identify participants’ needs and risk-factors. The survey also offers a resource guide, Dr. Horowitz says, answering questions such as “What are the resources for food? What are the resources if you are a survivor of domestic violence, and you can’t get out of your house? What do you do if you are homeless? What do you do to help your kids learn? What do you do if you are pregnant and you have COVID-19?”

And studies are underway on subjects including:

The impact of gender-affirming hormone treatment on the clinical course of COVID-19 in transgender and gender-nonbinary patients;
Health outcomes for those living with HIV and COVID-19;
How patient care via telehealth can be delivered equitably and narrow the digital divide.

The New York City Department of Health reports that 81 percent of COVID-19 cases are in the Bronx, Brooklyn, and Queens, with higher numbers in neighborhoods that are lower income and have more underserved residents. Only 12 percent of cases are in Manhattan, and there are signs of health disparity there as well, “right in our area, since The Mount Sinai Hospital is at the border of East Harlem and the Upper East Side,” Dr. Horowitz says. The DOH reports that as of May 18, in the 10029 zip code—East Harlem—there were 1,698 COVID-19 cases and 182 deaths, in a population that is 84 percent African-American and Latino with a median yearly income of $34,000. The toll was markedly lower in the adjacent 10028 zip code—the Upper East Side—where there were 603 cases of COVID-19 and 34 deaths, in a population that is 71 percent non-Hispanic white with a median income of $114,000.

The Mount Sinai Health System is well positioned to collect and study its own data on health care disparity because of years of groundwork led by the Office for Diversity and Inclusion, says Gary C. Butts, MD, Chief Diversity and Inclusion Officer, Mount Sinai Health System, and Dean for Diversity Programs, Policy, and Community Affairs, Icahn School of Medicine. “Understanding disproportionality is important,” Dr. Butts says. “With the data we have assembled, we can study it better, and we can be positioned to close the gaps that we have been talking about for a long time. It’s the right thing to do, and it’s the smart thing to do.”

Collecting Data

Pamela Y. Abner, MPA, Vice President and Chief Administrative Officer, Office for Diversity and Inclusion, spearheaded the effort to make it a standard procedure across most of the Health System to collect data in Mount Sinai’s patient registration systems on race, ethnicity, language, and sexual orientation and gender identity. The data are available to clinicians and researchers to enhance patient care and further study on an innovative Disparities Dashboard, created with leaders including Dr. Richardson and Nina A. Bickell, MD, MPH, Professor of Population Health Science and Policy, and Medicine.

“In the case of COVID-19, it appears that African-American patients were coming into the hospital sicker,” says Ms. Abner, citing preliminary findings. “We will now be able to analyze our data to determine if there are socioeconomic factors that impact outcomes within our most vulnerable populations. For example, we might look at the relationship between race/ethnicity and those who were more acutely ill, based on ICU numbers or length of stay, and consider how that may have impacted clinical outcomes.”

Dr. Richardson has experienced the toll of the COVID-19 pandemic more directly than most. In addition to her administrative and research duties, she treats patients in the Emergency Department at The Mount Sinai Hospital and at Elmhurst Hospital, and recently recovered from COVID-19 herself. “Now that we have come through the worst of the COVID-19 pandemic, it is important that we thoroughly investigate all of the causes of its disproportionate impact on racial/ethnic minorities and vulnerable communities, which are layered on top of many longstanding, pre-existing health and health care disparities,” Dr. Richardson says.

The overarching goal is addressing needs of populations at risk of COVID-19 and other health issues, which includes many members of the Mount Sinai community. “Mount Sinai is the biggest employer in East Harlem,” Dr. Horowitz says. “These are the people who are delivering food, delivering medicine, driving people around, working as home attendants. These are heroes; these are the people who have not stopped. They are not staying home in isolation, because they can’t.”

“At this point, our ability to understand, partner with, and serve those who are most vulnerable to COVID-19 is a reflection of our commitment as human beings, as researchers, as clinicians and as a Health System,” Dr. Horowitz says. “We are only as good as how we care for our most vulnerable populations.”

Overwhelming Antibody Response to COVID-19 is an Encouraging Sign, Researchers Say

May 13, 2020 | COVID-19, Featured, Research

Ania Wajnberg, MD, left, with Nurse Manager, Patricia Lazio, RN.

More than 99 percent of individuals who fully recovered from COVID-19 and had mild to moderate symptoms that did not require hospitalization went on to develop antibodies, according to a new study by researchers at the Mount Sinai Health System. The team looked at 1,343 people who either had confirmed cases of the disease or were suspected to have the disease between March 26 and April 10, 2020.

The study also showed that these IgG antibodies, or Immunoglobulin G—which appear after an acute infection and have the potential to confer immunity and protection against reinfection—were optimal for use in testing three to four weeks after the onset of COVID-19 and two weeks after the disease resolved.

“While we don’t know for certain whether having antibodies confers immunity at this point, or how long immunity would last, we are very encouraged that even those people who had mild cases of the disease did produce antibodies,” says the study’s first author, Ania Wajnberg, MD, Associate Professor of Medicine (General Internal Medicine) at the Icahn School of Medicine at Mount Sinai.

The encouraging findings support the potential of antibody-based blood tests to help understand the spread of COVID-19, the disease produced by the SARS-CoV-2 virus. The testing would provide lawmakers with a better understanding of how many people may possibly be immune and might be able to safely return to work as economies begin to reopen. At this time, there remains limited data worldwide on the development of antibodies to SARS-CoV-2, particularly the formation of IgG.

Mount Sinai has tested more than 22,000 individuals for antibodies since late March, when it became one of the first institutions in the world to begin treating COVID-19 patients with antibody-rich plasma from individuals who recovered from the disease. Mount Sinai identified individuals who had high titers, a measure of the concentration of antibodies, and referred them to the New York Blood Center, where they donated their plasma. As of May 11, more than 350 patients had received this convalescent plasma therapy through Mount Sinai, which is currently compiling data on the program.

The study also found that 19 percent of those who had recovered from COVID-19 still had evidence of the virus after receiving a nasopharyngeal swab of the back of their nose and throat. This has raised some concerns among patients who thought they may have been reinfected.

“More evidence is showing that people probably don’t need to be stressed about these positive swabs,” says Dr. Wajnberg. “We don’t know for certain why almost 20 percent of people had evidence of the virus weeks out from their symptoms. It is possible there’s some shedding of the virus still going on, but it is also possible that the test is picking up dead viral fragments. The scientific community is looking into this because it has major implications as to whether you need a negative swab to be cleared from this disease, which more people are thinking you don’t.”

One of the study’s authors, Florian Krammer, PhD, Professor of Microbiology at the Icahn School of Medicine at Mount Sinai, developed the antibody test that Mount Sinai uses. He says, “If you have higher titers you start to see neutralization. I can’t tell you that having a certain level of titers is protective against the virus, but we know from the vast majority of viral infections that neutralizing antibodies do protect you from getting infected. There are four human coronaviruses that give you a common cold, and in studies of those you get antibodies for one to three years and are protected during that time. In some cases you’re protected from getting reinfected, in other cases you might get a little infected but not have symptoms, and in other cases you may have symptoms but they’re much milder.”

In related news, the Mount Sinai Health System and California-based Sorrento Therapeutics, Inc. recently agreed to jointly develop antibody products that would act as a “protective shield” against SARS-CoV-2 coronavirus infection, potentially blocking and neutralizing the activity of the virus in at-risk populations, as well as recently exposed individuals.

Large-Vessel Stroke and COVID-19 in Young Patients: New Insights

May 11, 2020 | COVID-19, Featured, Patient Stories, Research

The Icahn School Medicine at Mount Sinai team studying the relationship between stroke and COVID-19 included, from left, Thomas J. Oxley, MD, PhD; Johanna T. Fifi, MD; and J Mocco, MD, MS.

Cerebrovascular stroke specialists at the Icahn School of Medicine at Mount Sinai have reported on five patients younger than 50 years of age who presented to the Mount Sinai Health System in New York City with large-vessel stroke and COVID-19, surprising observations that were documented in The New England Journal of Medicine (NEJM) on Tuesday, April 28, 2020. Significantly, they have also determined that stroke patients may be delaying emergency care because of fear of COVID-19.

Large-vessel stroke, the most devastating form of stroke, occurs when there is a large blood clot in a major artery of the brain. It may cause severe symptoms in the patient and, when not diagnosed or treated quickly, may result in death or major disabilities. This form of stroke is typically seen in patients older than age 50.

“As the pandemic surged, we noticed a lot of the patients coming in for stroke were very young, and some of them did not have any traditional risk factors for stroke—but they were testing positive for COVID-19,” says the study’s senior author, Johanna T. Fifi, MD, Associate Director of the Mount Sinai Cerebrovascular Center, Director of Endovascular Stroke, and Associate Professor of Neurosurgery, Neurology, and Radiology. “We realized we had seen five young people with large vessel stroke within two weeks, and that was not usual,” adds Dr. Fifi. “By comparison, every two weeks over the previous 12 months, our service had treated, on average, less than one [0.73] patient younger than 50 years of age with large-vessel stroke.”

The patients described in the report were 33, 37, 39, 44, and 49 years old who presented to Mount Sinai during a two-week period, from March 23 to April 7, 2020. First author Thomas J. Oxley, MD, PhD, Instructor in Neurosurgery, and a specialist in vascular neurosurgery, was in the process of removing a blood clot from one patient. He was threading a tiny device through the artery to retrieve the clot, using an imaging monitor to guide him, and then he saw, he says, “There were new clots forming around the existing clot, in real time.” This was a very unusual finding.

While such observations are limited, and did not receive full peer review, NEJM says that it is sharing case reports like these that offer important teaching points or novel findings to communicate information on the global clinical effort against COVID-19. J Mocco, MD, MS, Director of the Cerebrovascular Center for the Mount Sinai Health System, Vice Chair of Neurosurgery, and Professor of Neurosurgery, says these five cases served as “an alert” to his stroke peers. The discovery of clots forming in the small vessels of many organs—in the lungs, heart, liver, and kidney—had already been reported in COVID-19 patients by several physicians from around the world, including pulmonologists and cardiologists at Mount Sinai.

One case highlighted in the NEJM report was that of a 33-year-old patient—a female who was described as previously healthy, and not having any of the usual risk factors for stroke.

She had reported symptoms of cough, fever, and chills for one week—possible symptoms of COVID-19—which were followed by progressive slowing or slurring of speech, with both numbness and weakness in the left arm and left leg over a period of 28 hours—symptoms of stroke. When she presented to Mount Sinai Brooklyn, her score on the National Institutes of Health Stroke Scale (NIHSS) was 19 (scores range from 0 to 42, with higher numbers indicating greater stroke severity). Dr. Mocco described it as “profound” stroke—the type, he said, that has the potential to result in the most severe physical and cognitive deficiencies.

Adding to the medical challenge was this patient’s delay in seeking medical care. Large-vessel strokes are very treatable, says Dr. Oxley, especially when treated within 6 hours, and up to 24 hours of the onset of symptoms. This patient, however, took more than a day to seek medical care. “She delayed seeking emergency care because of fear of COVID-19,” the report says. “She told us that she lives with elderly relatives, and she was afraid of exposing her family by going to the hospital, so she stayed home,” says Dr. Fifi.

Computed tomography (CT) and CT angiography showed a partial infarction of the right middle cerebral artery with a partially occlusive thrombus (blood clot) in the right carotid artery in the neck. Significantly, patchy ground-glass opacities in the lungs—a finding characteristic of COVID-19—were also seen on CT angiography. Testing to detect SARS-CoV-2, the virus that causes COVID-19, was positive.

The patient received antiplatelet therapy, which was subsequently switched to anticoagulation therapy. After a repeat CT angiography on Day 10 showed a complete resolution of the blood clot, the patient was discharged to a rehabilitation facility.

Among the four other patients, one was discharged home, another to a rehabilitation facility, one to the Mount Sinai stroke unit, and the fourth succumbed to his illness.

Since submitting their NEJM report, Dr. Mocco and his team have begun to analyze every stroke case that occurred while Mount Sinai hospitals were treating COVID-19 patients. “We saw a doubling in the rate of severe strokes, and more than half of the patients were positive for COVID-19,” he says. “And, we saw that they looked very different from the normal stroke population—they looked younger, and they were more likely to be men. It appears—very strongly—that there is an association here between the virus and forming blood-clots.” All of this requires more rigorous research, and the Mount Sinai stroke team will continue to observe and to collaborate on new investigations to increase understanding of the stroke and COVID-19 relationship.

In the meantime, each of them urges any individual who has stroke symptoms to seek immediate help. “Social distancing, isolation, and reluctance to present to the hospital may contribute to poor outcomes,” they wrote in the NEJM report. “Two patients in our series delayed calling an ambulance because they were concerned about going to a hospital during the pandemic.” Adds Dr. Oxley: “You need to call the ambulance urgently if symptoms such as facial drooping, arm weakness, and speech difficulties appear.”

Some Severely Ill Children May Mount an Overly Aggressive Response to COVID-19

May 8, 2020 | COVID-19, Featured, Research

George Ofori-Amanfo, MD, Chief of the Division of Pediatric Critical Care at The Mount Sinai Hospital and Mount Sinai Kravis Children’s Hospital

Nine pediatric patients admitted to The Mount Sinai Hospital during the past two weeks, who either tested positive for COVID-19 or had antibodies, had severe abdominal pain and low blood pressure, which progressed to shock. Some of the patients also had clinical signs of myocarditis. This inflammation affects the heart muscle and the heart’s electrical system, reducing the heart’s ability to pump and causing abnormal rhythms, or arrhythmias. SARS-CoV-2, which causes COVID-19, is the first coronavirus associated with myocarditis.

Prior to their infections, the patients—six boys and three girls—did not have co-morbidities that would have put them at higher risk for disease, according to George Ofori-Amanfo, MD, Chief of the Division of Pediatric Critical Care at The Mount Sinai Hospital and Mount Sinai Kravis Children’s Hospital.

“These patients presented with very unusual symptoms,” says Dr. Ofori-Amanfo. “Until now, the pediatric patients who came to the Emergency Department with COVID-19 all had respiratory problems like the adults—dry coughs, difficulty breathing, and sometimes decreased oxygen saturation. In this recent series of patients, the children presented with abdominal pain, low-grade fever, vomiting, and in some cases diarrhea.” The pain was so severe that one child was sent to Mount Sinai to determine whether the problem was appendicitis, which was not the case. Another child was sent to the hospital for a CT scan to see whether the cause was inflamed abdominal lymph nodes. This was also ruled out upon closer examination.

Two of the nine pediatric patients also had a rash and conjunctivitis, which put their symptoms in a constellation of conditions that are similar to but not the same as Kawasaki disease, which causes blood vessels to become inflamed and also affects the heart. Both of these patients were among those with the least severe symptoms.

Dr. Ofori-Amanfo says that when the children and young adults progressed into a state of shock with low blood pressure, they did not respond to the traditional methods of resuscitation and large amounts of IV fluids, so the clinicians gave them high doses of blood pressure medication, which helped. Three of the patients required mechanical ventilation for shock and two of these patients also required mechanical cardiac support.

“This is a new phenomenon and it is rare. Perhaps these patients had mild symptoms of COVID-19 or were asymptomatic. We think what we’re seeing is a post-infectious process. It is an aggressive immune response to either the virus or some aspect of the viral infection that we don’t know yet. Because when you look at their lab profiles, the patients have very elevated inflammatory markers and this suggests an acute inflammatory response,” says Dr. Ofori-Amanfo. “The exaggerated immune response affects the heart function, which is mildly to moderately depressed, and their low blood pressure is a result of the hyper state of their immune system.”

At Mount Sinai, a team of specialists in areas that include pediatrics, immunology, hematology, infectious diseases, and basic science is treating this syndrome by targeting and modulating the overwhelming immune response and managing anticoagulation therapies for potential strokes. “This is a real entity, but it is rare, and we are hypervigilant and looking out for our patients,” says Dr. Ofori-Amanfo. “We think we have developed some therapies that are working. We have really smart, dedicated specialists working together. It is a great partnership.”

Other hospitals in the New York metropolitan region, around the country, and in Europe have reported smaller clusters of similar pediatric cases.

“We are studying the children to learn what predisposes them to developing this syndrome,” Dr. Ofori-Amanfo says. “These children had siblings. We don’t know why one child gets this but his brother or sister doesn’t.”

Outcomes Data Published from Large, Diverse COVID-19 Patient Study in NYC

May 7, 2020 | COVID-19, Featured, Research

Li Li, MD, Sema4’s Vice President of Clinical Information and an Assistant Professor at the Icahn School of Medicine at Mount Sinai

Sema4 scientists released results from an analysis of patients tested for SARS-CoV-2 at five hospitals in the Mount Sinai Health System. Spanning more than 28,000 patients, this is one of the largest and most racially diverse COVID-19 studies performed in the United States to date. The study findings were posted as a preprint on medRxiv.

The team at Sema4 analyzed de-identified electronic medical records from 28,336 patients tested for SARS-CoV-2 at Mount Sinai Health System hospitals in Manhattan, Brooklyn, and Queens between February 24 and April 15. Of those patients, 6,158 tested positive for the coronavirus and 3,273 were admitted to the hospital.

Consistent with other reports, this study confirmed that COVID-19 prevalence in African Americans and Hispanics is disproportionately high in New York City. However, for patients admitted to the hospital, the analysis found no differences in mortality rates based on ethnicity, indicating that inpatient care helps to address this health care disparity.

The team also identified several risk factors linked to increased mortality rates for COVID-19 patients, including age, oxygen levels, body mass index, and elevated creatinine, among others. Asthma was associated with longer hospital stays, but did not appear to be linked to increased mortality rates. The study, which found higher mortality rates at hospitals where patients had more severe cases upon entry, can also be used to guide neighborhood-based testing for SARS-CoV-2.

Li Li, MD, Sema4’s Vice President of Clinical Information and an Assistant Professor at the Icahn School of Medicine at Mount Sinai in the Department of Genetics and Genomic Sciences, who was one of the lead scientists on the project, commented: “In a thorough review of published studies investigating COVID-19 mortality rates, we found unintentional biases, such as small sample size, that limited the broader utility of the data. By including all patients tested at these five member hospitals and performing advanced statistical modeling including multivariate analyses, we have removed that bias and generated findings that should be more useful in improving the understanding of which clinical features track with disease progression and associated outcomes.”