The Jonas Brothers. From left, Joe, Nick, and Kevin Jonas.

Kevin and Danielle Jonas, Joe Jonas and his wife, Sophie Turner, and Nick Jonas and his wife, Priyanka Chopra Jonas, have donated $500,000 to the Mindich Child Health and Development Institute at the Icahn School of Medicine at Mount Sinai, to support pediatric research into COVID-19 at a time when a rare syndrome is affecting children who become severely ill about four weeks after they seemed to have recovered from the disease.

Since early May, The Mount Sinai Hospital has admitted almost 20 patients between the ages of five and twenty, with multi-system inflammatory syndrome in children (MIS-C) associated with coronavirus disease 2019 (COVID-19). It is defined as a syndrome in patients under the age of 21, with onset of fever for at least one day, laboratory evidence of inflammation, and severe illness with multi-system involvement.

George Ofori-Amanfo, MD, Chief of the Division of Pediatric Critical Care at The Mount Sinai Hospital and Mount Sinai Kravis Children’s Hospital, says Mount Sinai has developed a “strong and standardized process” for caring for these pediatric patients. This streamlined approach includes every phase of care, from the initial presentation in the pediatrician’s office or the emergency department through the entire hospitalization, discharge, and follow-up. It includes specific therapies and procedures, handoffs between the different levels of care within the hospital, and video phone calls with patients after they have been discharged and returned home.

The gift from the Jonas family will be used to support research into this inflammatory syndrome that is being conducted at the Icahn School of Medicine in areas that include genetics, bioinformatics, precision immunology, microbiology, and pediatrics.

Dusan Bogunovic, PhD, and Conor Gruber, MD/PhD candidate, Icahn School of Medicine at Mount Sinai

The effort is being spearheaded by Dusan Bogunovic, PhD, Associate Professor of Microbiology, and Pediatrics, and Director of the Center for Inborn Errors of Immunity, which is part of the Mindich Child Health and Development Institute. “We are studying two main questions,” says Dr. Bogunovic. “What causes this severe immune response that leads to MIS-C associated with COVID-19 in some children? And why do most other children seem to handle the SARS-CoV-2 virus so easily?”

This second question continues to puzzle physicians and scientists. Most children with COVID-19 appear to be asymptomatic and do not display the dry cough or trouble breathing that adults do.

Mount Sinai’s scientists will be characterizing the immune response of children at the RNA and DNA level to understand the disease pathology in cells by studying patients with the syndrome, in addition to healthy children. They will explore whether genetics plays a role in determining which children may be more susceptible to MIS-C; whether the types of antibodies these children produce influence MIS-C; and what in the immune system is driving the children’s clinical presentation. Is it the hyper-activation of their immune systems that triggers a cytokine storm or the specific cell subtype that drives pathogenesis?

“Through this work, we are striving to keep all of our children as safe as possible. The lessons we learn are sure to inform care for infections in children that go beyond COVID-19,” says Dr. Bogunovic.

Dr. Ofori-Amanfo says, “It is paramount that as we take care of our patients, we partner with our research teams and bring in their perspective in order to understand the underlying disease progression and treatment options.”

He adds that even though MIS-C is rare, if parents see their children developing abdominal pain in association with a fever or rash they should call their pediatrician immediately and not be fearful about coming to the hospital, if they need to. “The hospital is a safe place,” he says. “We are taking all of the infection prevention measures to ensure that our patients and staff are safe. We are committed to providing patients with the best care.”

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.”

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.