In Mount Sinai’s study, the children were age 12 on average and otherwise healthy.
MIS-C is a rare, potentially life-threatening syndrome that occurs about five weeks after children have been infected by the SARS-CoV-2 virus, which causes COVID-19. Most of the children are actually asymptomatic for COVID-19, but when they develop MIS-C they are hospitalized with shock, excessive blood clotting, gastrointestinal symptoms, and heart dysfunction.
In a new development, researchers at the Icahn School of Medicine at Mount Sinai have identified a unique pattern of immune responses that characterize multisystem inflammatory syndrome in children (MIS-C) and could eventually serve as a biomarker, or reliable indicator that would help diagnose the disease.
The Mount Sinai scientists discovered this unique pattern of immune responses by using sophisticated single-cell technology to analyze the blood circulating through the bodies of nine MIS-C patients who were treated at Mount Sinai Kravis Children’s Hospital between late April and June 2020. The researchers found elevated levels of specific cytokines—molecules that regulate immunity and inflammation—and chemokines—signaling proteins—that distinguished the MIS-C patients. The children were age 12 on average, otherwise healthy, and almost equally divided between boys and girls.
“In order for us to really understand MIS-C, we had to describe the disease, and this is the first in-depth mapping of what the disease looks like,” says Dusan Bogunovic, PhD, Associate Professor of Microbiology, and Pediatrics, and Director of the Center for Inborn Errors of Immunity, part of The Mindich Child Health and Development Institute and Precision Immunology Institute. Dr. Bogunovic is the corresponding author of a Mount Sinai study that describes the findings in detail. The paper was posted to the pre-print server medRxiv.org last summer and is now published in Cell.
Dusan Bogunovic, PhD
Conor Gruber, an MD/PhD candidate at the Icahn School of Medicine, a member of the Bogunovic lab, and the paper’s first author, says, “We have mapped autoimmune parameters at an unprecedented level. Now we need to know if this autoimmune component causes the disease or is just a byproduct of MIS-C. We’re actively researching this.” Autoimmunity occurs when an individual’s antibodies mistakenly attack their body. Since the body’s adaptive immune response to disease usually forms after several weeks—the same amount of time it takes for children to develop MIS-C—the researchers believe this is likely where the problem lies within the immune system.
When the initial cases of MIS-C began surfacing in the spring, several weeks after the surge of adult COVID-19 cases in the New York metropolitan area, MIS-C was considered an atypical form of Kawasaki disease, an acute systemic inflammation of the blood vessels, mainly affecting very young children. Since then, the World Health Organization has classified MIS-C as a distinct syndrome. The Mount Sinai study found that “overlapping features are striking, suggesting that MIS-C may lie along a spectrum of Kawasaki disease-like pathology.”
Although further studies into the causes of MIS-C are needed, says Dr. Bogunovic, the good news is that widely accepted protocols are in place for the successful treatment of the disease. He is less certain, however, about whether a child’s predisposition to MIS-C portends a predisposition to different autoimmune disorders down the line or will interfere with the ability to successfully receive a COVID-19 vaccine.
“All of these postulates need careful, methodical, and well-controlled experimental dissection,” the study authors wrote. “Until then, MIS-C remains scientifically puzzling, but therapeutically manageable.”