In the early days of the COVID-19 outbreak, it seemed that children were far less likely to develop serious problems from the disease than adults. Then in mid-March, hospitals started reporting an unusual inflammatory syndrome in children that seemed to be related to COVID-19, now known as multisystem inflammatory syndrome in children (MIS-C).
MIS-C can cause inflammation of many parts of the body, including the heart, lungs, brain, skin, eyes, kidneys, and gastrointestinal organs. Some of the most serious complications of MIS-C involve the heart, including ventricular dysfunction, coronary artery aneurysms, and arrhythmias. Children may also have partial or complete features seen in Kawasaki disease (KD).
As of mid-July, the Centers for Disease Control and Prevention (CDC) had received reports of 342 cases and 6 deaths from MIS-C in 36 states and Washington D.C. There are still many unanswered questions about MIS-C, but from the start, clinicians and researchers at the Boston Children’s Hospital Heart Center have been on the front lines, diagnosing and treating patients, as well as looking for answers about this rare and mysterious syndrome.
“Boston was hit early in the pandemic, so hospitals and institutions in other states are looking to us for guidance,” says Jane Newburger, MD, MPH, associate cardiologist-in-chief and director of the Kawasaki Program at Boston Children’s. “Long-term effects of MIS-C on the heart are as yet unknown, so we are systematically following affected children and teens for their heart function, coronary artery status, and conduction system/arrhythmias.”
Cardiology MIS-C team: Providing clinical leadership
To address these issues and develop guidelines for proper follow-up care, the Cardiology MIS-C team at Boston Children’s serves as a national resource for parents and physicians. The team includes international experts on this difficult-to-diagnose condition.
“A member of our team is on call 24-hours-a-day, seven days a week, to provide consultation and care for other providers, children, and their families,” says Newburger.
Along with Newburger, the MIS-C team includes Kevin Friedman, MD, Audrey Dionne, MD, Sarah de Ferranti, MD, and David Fulton, MD. In addition, Christina VanderPluym, MD, provides expertise in the coagulopathy in children with MIS-C and Annette Baker, RN, MSN, PNP, coordinates the program. The team has also been working closely with Mary Beth Son, MD; Pui Lee, MD, PhD; and Meghan Day-Lewis, NP, in the Rheumatology Program and specialists in the Division of Infectious Diseases to tailor treatment to each child’s individual cardiac status.
In addition, Friedman says the team is uniquely positioned to care for MIS-C patients because of its long-standing Kawasaki Disease Program. “We’ve been a leader in taking care of Kawasaki disease patients for the past 40 years,” says Friedman. “So we already have that infrastructure set up, including a multidisciplinary team of cardiologists who specialize in anticoagulation and heart failure, as well as rheumatologists and infectious disease doctors already in place. The novelty of this disease has left everyone with a lot of clinical and research questions, and our experience makes us well-positioned to answer them.”
Newburger says clinicians should reach out to the team with any questions about their patients and MIS-C. “We can arrange to see patients, we can do echocardiograms, and we can also do virtual visits to discuss symptoms and questions,” she says. “We’re here for questions and to help providers decide if evaluation is needed.”
As of mid-July, Boston Children’s has seen 40 patients who meet the strict definition for an MIS-C diagnosis according to the Massachusetts Department of Health, as well as at least 40 more who have been screened. Although criteria for diagnosis vary somewhat, they all include fever, laboratory evidence of inflammation, organ dysfunction, and association with COVID-19. “We suspect that immunologic phenomena in response to SARS-CoV-2 are relatively common, and that MIS-C is just the tip of an iceberg,” says Newburger. She says that under that tip may be many more children who have other immune symptoms, or who don’t quite meet the definition of MIS-C.
Leaders in MIS-C research
As the COVID-19 pandemic marches forward, several clinicians from the MIS-C team are leading and involved in research projects to learn more about this mysterious illness.
- Newburger is leading a very large, national, multicenter project that is being funded through the NIH and is going to look at the time course and spectrum of heart disease symptoms in patients who have MIS-C. This project will examine what happens over the long term to coronary artery changes, heart function, and arrhythmias in children diagnosed with MIS-C.
- Audrey Dionne has done work on arrhythmias and conduction problems in children with MIS-C, and how the electrical system of the heart does over time.
- Friedman and Dionne are the first and senior author in describing the team’s experience with the first 25 MIS-C patients at Boston Children’s. That paper will be published in Pediatrics.
- Newburger, Friedman, and Dionne, along with colleagues in rheumatology have published the team’s global experience with MIS-C patients in the Journal of Clinical Investigation, including how their laboratory values compare to those of patients with Kawasaki disease.
- Newburger and others on the team are involved in a study through the Pediatric Heart Network and funded through the NIH. As part of this study, Freidman will be running an echocardiographic core laboratory, getting echos from providers across the country to interpret and evaluate.
- Friedman is senior author on in multi-center piece that will suggest how patients should be followed clinically.
- The team is providing cardiac phenotyping, to see what do the hearts of these patients look like. “We’re working closely with clinicians in other divisions who are helping us understand the mechanisms that might determine that phenotype,” says Newburger. “As cardiologists, we very focused on the heart, but we also need to understand why some people are so affected and others are not.”
- The team is also collaborating with researchers in rheumatology to learn more about how the immune system expresses itself. “We want to learn how it’s different in MIS-C vs. Kawasaki, vs. toxic shock,” says Newburger.
The team is well aware that when it comes to COVID-19 and MIS-C, they have to remain curious and agile. “For first time in our lifetimes, there is a new virus that the human race has not been exposed to,” says Newburger. “Everyone is getting it at the same time, so we’re seeing a spectrum of symptoms. We are learning more every day, and we want to stay on the cutting edge of knowledge.”
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