Members of the Pathology Department’s autopsy study, from left: Elisabet Pujadas, MD, PhD; Zachary Grimes, DO; Kenneth Haines, MD; Clare Bryce, MBChB; Mary Fowkes, MD, PhD; and Carlos Cordon-Cardo, MD, PhD.

Since March 8, when Mount Sinai West hospitalized its first patient with COVID-19, more than 8,000 individuals with the disease have been admitted to the Mount Sinai Health System. During that time, the medical community’s knowledge of COVID-19 has evolved from seeing it as a respiratory illness to understanding its effect on the blood vessels and multiple organs.

“Mount Sinai has been the epicenter of the epicenter,” says Dennis S. Charney, MD, Anne and Joel Ehrenkranz Dean, Icahn School of Medicine at Mount Sinai, and President for Academic Affairs, Mount Sinai Health System. “We’ve been attacking COVID-19 from many different perspectives and we’ve made a lot of progress in a short amount of time.”

Indeed, as Mount Sinai’s front-line doctors, nurses, and others faced a tsunami of sick patients entering their hospitals, they were able to improve patient outcomes by working closely with their colleagues in other specialties and in laboratories at the Icahn School of Medicine at Mount Sinai. Through careful observations and investigations they have come to define COVID-19 as a new disease that attacks the endothelial cells that line the body’s blood vessels. How the disease plays out in each individual depends largely on the state of their immune system and whether they have co-morbidities, such as obesity, hypertension, or heart disease, which affect blood flow within the body. Approximately 80 percent of people with COVID-19 are able to recover without hospitalization.

“This is a disease we had not seen before,” says Carlos Cordon-Cardo, MD, PhD, the Irene Heinz Given and John LaPorte Given Professor and Chair of the Lillian and Henry M. Stratton-Hans Popper Department of Pathology, Molecular and Cell-Based Medicine, who developed accurate, widespread testing throughout the Health System to help diagnose and manage COVID-19. “Initially, it was conceptualized as a viral respiratory illness. But now we know it causes endothelial damage.” This damage leads to excessive blood clots throughout the body, which can also lead to multi-organ failure. There is a strong immune component to the disease, as well, which is led by macrophages or scavenger blood cells that eat viruses and dead cells and can be very difficult to control, even with targeted immunotherapy.

A clearer understanding of the biology of the disease and the range of organ damage inflicted by COVID-19 was provided by the Department of Pathology, which “uncompromisingly performed as many autopsies as possible, and conducted over 90 in COVID-19-positive patients,” says Mary E. Fowkes, MD, PhD, Professor of Pathology, Molecular and Cell Based Medicine, and Director of Mount Sinai’s Neuropathology and Autopsy Service.

Pulmonary embolism in 3D.

Recently, Drs. Cordon-Cardo and Fowkes published a study of 67 individuals with the disease who were treated at Mount Sinai between March 20 and April 29, 2020. “We expected severe changes in the lungs, which we were able to confirm,” says Dr. Fowkes. “But one of our surprising findings in the lungs was that in addition to the viral infection, there was a secondary bacterial infection that made it worse.” Another surprising finding, she says, was that in a number of cases, the patients had experienced large pulmonary embolisms that traveled directly to the lungs and caused sudden death.

The pathologists also found blood clots in the small blood vessels of many major organs, as well as the central nervous system, and identified a syndrome similar to hemophagocytic lymphohistiocytosis (HLH), a rare condition in which the body makes too many activated immune cells, specifically macrophages and lymphocytes, produced in the bone marrow. HLH can overlap with Kawasaki syndrome, which has been compared to a rare reaction seen in children who seem to recover from COVID-19 but go on to experience severe symptoms that include heart inflammation, low blood pressure, and trouble breathing.

Initially, doctors were concerned that people with asthma would be at greater risk for severe symptoms due to the disease’s respiratory component. But that did not turn out to be the case, even though the disease spreads from one person to another through respiratory droplets. Another surprising finding was that in comparison with the heart, brain, lungs, and liver, the kidneys were less affected by blood clots. Researchers think that may be because the ACE2 receptor—to which the SARS-CoV-2 virus attaches in order to enter the cell—is less prevalent in the kidney’s network of blood vessels.

“In reality, it’s the patients who have heart disease who seem to be at greater risk,” for severe outcomes, says Dr. Fowkes. “Diabetes accelerates vascular disease with plaque located in blood vessels throughout the body. So that if you have pre-existing damage to blood vessels you would be at greater risk. Heart disease is similar. If you have hypertension you see damage to tissues that surround the blood vessels and to the blood vessels themselves.”

Adam Bernheim, MD, Assistant Professor of Diagnostic, Molecular and Interventional Radiology at the Icahn School of Medicine at Mount Sinai, was one of the first U.S. radiologists to review the lung CT scans of COVID-19 patients from China. Since early March, he says, doctors have begun to understand the breadth of injuries that COVID-19 inflicts on the body and its relentlessness in doing so.

“The patterns of injury to the body run the spectrum from blood clots and pulmonary embolisms to pneumonia and abdominal issues,” he says. Some patients, including those in their 20s and 30s, take months to heal and others develop permanent scarring in their lungs. With many diseases he says, the body takes a big hit and then is able to repair itself. But COVID-19 can “cause continuous injury to the lungs over weeks. It just keeps hitting and hitting.”

David L. Reich, MD, President of The Mount Sinai Hospital and Mount Sinai Queens says the last three months illustrated how well the Mount Sinai Health System functioned in ensuring that patients in each of the seven Health System hospitals treating COVID-19 patients received the life-saving care they needed. In addition, he says, “The Icahn School of Medicine, with its top scientists, was completely in lockstep with the largest health system in New York City. We were able to do things together that we never would have been able to do separately. And because of that, we were able to change the course of therapeutics for this disease, as well.”

The Mount Sinai Health System has had the largest worldwide experience with convalescent plasma therapy and was the first to demonstrate its benefit in this disease, he says.  Additionally, Mount Sinai instituted a policy to administer anticoagulant treatment, which has also been beneficial. Through its clinical trials infrastructure, Mount Sinai had early access to the antiviral drug remdesivir, the anti-inflammatory drug sarilumab, and allogeneic stem cell therapy.

During the height of the pandemic, as other health systems “were doing their best to provide some level of care while not being overwhelmed, Mount Sinai was innovating,” says Dr. Reich. “Mount Sinai was applying science and showing improved outcomes with therapeutic innovations in a way that demonstrated we are one of the best institutions in the world, especially with regard to COVID-19 care.”

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.”