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.”

Miriam Merad, MD, PhD

Miriam Merad, MD, PhD, a pioneering immunologist at the Icahn School of Medicine at Mount Sinai, has been elected to the National Academy of Science (NAS), an honor that recognizes her transformational contributions to the fields of myeloid cell biology and innate immunity. Dr. Merad, the Mount Sinai Professor in Cancer Immunology and Director of the Precision Immunology Institute, joins an elite group of international scientists with membership in the NAS.

In a landmark study published in Science in 2010, Dr. Merad showed that macrophages—large white blood cells—arise from embryonic precursors that take residence in tissues prior to life where they play a distinct role in organ physiology and pathophysiology. This study, cited several thousand times, has had important clinical implications. Dr. Merad and her team also established the contribution of this macrophage lineage to cancer progression and response to treatment, and to inflammatory bowel disease, in studies published in prominent journals such as Science, Cell, and Nature.

In addition to her work on macrophages, Dr. Merad is known for her work on dendritic cells, a group of cells that control adaptive immunity. She identified a new subset of dendritic cells, which is now considered a key target of antiviral and antitumor immunity. In a May 2020 study in Nature, she and her team revealed novel therapeutic targets to enhance dendritic cell-mediated antitumor immunity.

“I am thrilled to have been elected to the National Academy of Science and proud to represent Mount Sinai in immunology,” says Dr. Merad, who joined Mount Sinai’s faculty in 2004. She says her parents—both scientific and medical professionals who were educated in France and practiced in Algeria—raised her “to respect the transformational power of science.”

She adds that Mount Sinai helped foster her passion by giving her the freedom to grow and pursue her work. “Mount Sinai has a culture that empowers junior faculty. I tell junior scientists, ‘If you want to be transformative and innovate early in your career, this is the place to be,’” she 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, says, “Dr. Merad’s discoveries have helped changed the course of medical treatments and her work continues to shed light on the way the human immune system responds to disease.”

In May, after receiving word of her election to the NAS, Dr. Merad shared the news with all of the former and current postdoctoral fellows in her lab. Many of her original fellows, who continue to collaborate with her on research, are now established investigators in institutions that include Stanford University, the University of Massachusetts-Amherst, the University of Toronto, the University of Zurich, and Charité in Berlin. “I told them that this election recognizes the many hours they spent in my laboratory and I thanked them for everything we have done together,” she says.

A NEW COVID-19 RESEARCH EFFORT

Under Dr. Merad’s leadership, Mount Sinai has become an international hub for the study of the human immune system. She developed Mount Sinai’s Human Immune Monitoring Center (HIMC) as one of the world’s most sophisticated research centers; it uses cutting-edge single-cell technology to understand the contribution of immune cells to major human diseases or treatment responses. HIMC participates in several major consortia funded by the National Institutes of Health.

This center will now play a key role in helping Dr. Merad and her colleagues understand why some patients develop severe forms of COVID-19 and some do not. For the past six weeks, she has led a major effort at Mount Sinai with her colleague Alexander Charney, MD, PhD, Assistant Professor of Psychiatry, Genetics and Genomic Sciences, Neuroscience, and Neurosurgery, to collect blood samples from 500 hospitalized COVID-19 patients. The collection is still ongoing.

She says, “We will use the HIMC to analyze the inflammatory response that is triggered in our patients as a result of COVID-19, as well as the adaptive immune response to the virus.” Her goals for the project include the ability to predict which patients will develop a severe inflammatory response and then find ways to prevent and treat it.

Yet, she adds, even when some patients recover from the disease, they continue to have negative effects. “We do not know if it’s because inflammation persists and does not resolve. There is still a lot to learn. We will be following these patients for a long time because we need to monitor the resolution of inflammation and the quality of the immune response that these patients develop and see whether this response is protective.”