Multisystem inflammatory syndrome in children (MIS-C) is a complex syndrome associated with SARS-CoV-2, the virus that causes COVID-19. Children who develop MIS-C may experience diarrhea, vomiting and severe cardiovascular problems in addition to respiratory problems. Other symptoms include conjunctivitis, skin rash, swollen hands or feet, cracked lips and a red tongue — signs typically associated with classic Kawasaki disease, an inflammatory disease that can cause coronary artery aneurysms. Also confounding this clinical picture, some children with MIS-C experience neurologic symptoms such as headache, unusual sleepiness, disorientation and confusion.

Needless to say, clinicians are significantly challenged when it comes to diagnosing and managing these patients, and predicting which children need hospitalization and which will become critically ill.

Now, thanks to a four-year, $4.8 million grant from the National Institutes of Health, Johns Hopkins Medicine researchers hope to dramatically improve that situation by designing predictive models for MIS-C.

“Normally the clinical management of patients with this novel syndrome is very difficult — it affects multiple systems and there is a lot of overlap with different diseases and signs and symptoms that are still evolving,” says Shelby Kutty, M.D., Ph.D., M.S., the Helen B. Taussig professor and director of pediatric and congenital cardiology at the Johns Hopkins University School of Medicine. “Treatment at the onset and the epidemiology of this disease are still very new, presenting the need for salient prediction models for diagnosis and figuring out which patients are likely to develop new problems.”

Kutty and lead principal investigator Cedric Manlhiot, Ph.D., assistant professor of pediatrics at the Johns Hopkins University School of Medicine, aim to produce such predictive models for a syndrome that doesn’t act in a predictive way. They’ll do this — in partnership with the International Kawasaki Disease Registry (IKDR) — through the Johns Hopkins Cardiovascular Analytic Intelligence Initiative (CV-Ai²), which uses artificial intelligence (AI) and machine learning tools to turn real-time clinical data into prediction models that can help forecast patient outcomes. Kutty is chair and Manlhiot is director of the CV-Ai².

“The goal of the CV-Ai² is to find better ways to utilize data and design solutions for important clinical problems, which in turn are directly evaluated at the physician and patient level,” Manlhiot says. The initiative was created by the Blalock-Taussig-Thomas Pediatric and Congenital Heart Center at Johns Hopkins Children’s Center.

The first goal, explains Manlhiot, is to develop algorithms that clinicians can use in managing patients with MIS-C. During the first two years, patient data collected by the IKDR’s consortium of 19 hospitals will be used to help create the algorithms employing AI-based models for diagnosis, treatment and outcome prediction. In the third and fourth years, the performance and clinical utility of these models will be evaluated in a predictive decision support system, adding real-time epidemiological surveillance data.

“Ultimately, by year four, we’ll establish an interface that can be deployed in Epic [a widely used electronic medical record system] and similar records with clinical data that can aid diagnosis and treatment,” says Kutty.

Because MIS-C has some similarities with Kawasaki disease in its presentation, the strategic partnership with the IKDR will provide an established data collection platform and make use of substantial clinical and research expertise.

Pointing to interest from some 40 other hospitals in the United States as well as hospitals in South America, France, Italy, the United Kingdom, Taiwan and India, Kutty concludes that this work will grow the IKDR consortium and improve care and outcomes globally for children with MIS-C.

“Based on what we have gathered so far, this should lead to a meaningful prediction for patients all over the world,” says Kutty.

Redonda G. Miller, M.D., M.B.A., president of The Johns Hopkins Hospital, calls the awarding of this NIH grant a much needed “game changer” for children with SARS-CoV-2 related disease.

Kutty and Manlhiot are available for interviews.

This story is adapted from a Johns Hopkins Medicine website article written by Gary Logan.