COVID-19, MIS-C and Kawasaki disease share the same immune response
COVID-19, MIS-C and Kawasaki disease share the same immune response

COVID-19, MIS-C and Kawasaki disease share the same immune response

This study was led by UC San Diego School of Medicine researchers Pradipta Ghosh, MD, (left), Jane C. Burns, MD, (center) and Debashi’s Sahoo, PhD (right).

The advent of COVID-19 prompted doctors to run to define and treat the new disease, but they quickly discovered that it was not the only new disease caused by SARS-CoV-2. A subset of children infected with the virus also experienced abdominal pain, headaches, rashes, and vomiting. This new set of symptoms was labeled multisystem inflammatory syndrome in children (MIS-C) and had many of its pediatric patients requiring intensive care.

As the number of MIS-C increased, doctors began to notice its similarities with a pre-pandemic disease, Kawasaki disease (KD), which has puzzled pediatricians for more than 50 years. MIS-C and KD share many symptoms, including fever, rash, and bloodshot eyes, although KD can also lead to coronary artery aneurysms and heart attacks. Unlike MIS-C, which is associated with a specific virus, KD can be triggered by a variation of infectious and environmental stimuli.

To better understand how these inflammatory syndromes compare and contrast, researchers at the University of California San Diego School of Medicine collected blood and tissue samples from MIS-C and KD patients. Using artificial intelligence tools, they analyzed patterns of gene expression under both conditions and compared them with gene expression markers for COVID-19.

The study, published May 16, 2022 in Nature communication, reveals that MIS-C and KD are on the same immune response continuum as COVID-19, with MIS-C being a more severe version of the response than KD. Despite these underlying similarities, conditions differ in several laboratory and clinical parameters. Authors said the results could improve disease diagnosis, monitoring and treatment in pediatric patients.

“We want our immune system to protect us from harmful stimuli, but some children are genetically predisposed to react more intensely, leading to inflammation and unwanted symptoms across the body,” said co-author Jane C. Burns, MD, a pediatrician at Rady Children’s Hospital-San Diego and director of the Kawasaki Disease Research Center at the UC San Diego School of Medicine. “The sooner we can identify and understand the child’s inflammatory condition, the better we can tailor our delivery of lifesaving support.”

The research team has previously identified a set of 166 genes expressed in viral respiratory diseases, including COVID-19, one subgroup of which also corresponded to the severity of the disease. Researchers found that the same “gene signature” also applied to both MIS-C and KD, suggesting that the conditions all stem from a similar underlying mechanism, which involves rapid release of IL15 / IL15RA cytokines.

The team looked at a separate set of 13 genes used to identify KD and found that a computer program trained to look for this genetic signature could not distinguish between KD and MIS-C the samples.

MIS-C / KD graphics

Researchers from UC San Diego summarize the similarities and differences between COVID-19, MIS-C and Kawasaki disease, three conditions united by the same immunoassociated gene signature.

“We did not expect it,” said co-author Pradipta Ghosh, MD, a professor of medicine and cellular and molecular medicine at the UC San Diego School of Medicine. “We analyzed MIS-C and KD through the lens of two different gene signatures, and both experiments told us that these diseases are closely related.”

Ghosh said the two gene signatures probably represent different parts of the same broader immune response.

While the study provides a new unifying framework for these diseases, it also identifies a few subtle differences. For example, MIS-C patients had lower platelet and eosinophil counts, two features that can be measured from routine blood tests. And while many serum cytokines were similarly elevated under both conditions, a select few were more elevated in MIS-C than in KD samples.

The authors noted that therapies targeting some of these cytokines, including TNFα and IL1β, have already been approved by the US Food and Drug Administration (FDA) and are being tested as new treatments for MIS-C.

“We believe that our results have great potential to influence the planning of clinical trials immediately and also shape clinical guidelines and patient care down the line,” said the corresponding author Debashis Sahoo, PhD, Associate Professor of Pediatrics and Computer Science at the UC San Diego School of Medicine and the UC San Diego Jacobs School of Engineering.

Co-authors include: Gajanan D. Katkar, Chisato Shimizu, Jihoon Kim, Soni Khandelwal, Adriana H. Tremoulet, John T. Kanegaye, Pediatric Emergency Medicine Kawasaki Disease Research Group and Soumita Das, all at UC San Diego, as well as Joseph Bocchini of Willis- Knighton Health System.

This work was funded in part by the National Institutes of Health (grants R01-GM138385, R01-854 AI141630, R01DK107585 and R01-AI155696), UCOP-RGPO (grants R01RG3780, R00RG2DA and R40HLs, R40HLs and R40HLs and R40HLs, R40HLs and R40HLs and R40HLs),), Patient Outcomes Research Institute, Gordon and Marilyn Macklin Foundation, American Association of Immunologists Intersect Fellowship Program for Computational Scientists and Immunologists and a UC San Diego Stem Cell Center Pilot Award.

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