Unpacking the mystery of MIS-C

A new inflammatory disease related to COVID-19 is affecting children and young adults

Unpacking the mystery of MIS-C

3 Minute Read

A troubling rise in a severe inflammatory illness related to COVID-19 in children and young adults has doctors in the United States and abroad searching for answers.

The condition, known as multisystem inflammatory syndrome in children (MIS-C), causes swelling and pain in various organs, such as the heart, lungs, kidneys, brain, skin, eyes, esophagus, stomach and intestines. The Centers for Disease Control and Prevention (CDC) first issued a health advisory on May 14, cautioning doctors to be on the lookout for a constellation of symptoms that include fever, abdominal pain, vomiting, diarrhea, neck pain, rash, bloodshot eyes and lethargy.

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According to two studies from Boston Children’s Hospital and the New York State Department of Health, there have been approximately 300 cases of MIS-C in the U.S.

“This is truly a new type of syndrome that was unpredicted,” said Daniel Penny, M.D., Ph.D., chief of pediatric cardiology at Texas Children’s Hospital, who has treated several patients with MIS-C in his clinic.

Symptoms associated with MIS-C were initially reported by clinicians in the United Kingdom in late April and have since been identified in other European countries and the United States.

Although the exact cause of MIS-C is still unknown, many children diagnosed with the syndrome had been infected by or previously exposed to SARS-CoV-2, the virus that causes COVID-19.

“This lag between the primary infection and the inflammatory response is what is interesting,” Penny said. “What it appears to indicate is that this is not a manifestation of the primary infection with SARS-CoV-2 itself, but rather the body’s inflammatory response to the infection.”

Essentially, the immune system of MIS-C patients goes haywire in places it shouldn’t.

“What we think is happening is that, at some point in the recent past, the child was exposed to COVID-19. They might have had a mild infection, and the immune system responded to that infection appropriately, at first, but it … got into a positive feedback loop and couldn’t turn itself off,” said Michael Chang, M.D., a pediatric infectious disease specialist at Children’s Memorial Hermann Hospital who has treated several patients with MIS-C in the hospital.

Most children recover from MIS-C after being treated with immunoglobulins to reset the immune system, steroids and immunosuppressive drugs, such as anakinra and tocilizumab; however, in rare cases, the illness can lead to death.

Early on, doctors suspected the cases were driven by Kawasaki disease, a rare pediatric condition in which blood vessels become inflamed. Many of the features of MIS-C are similar to those of Kawasaki disease, the leading cause of acquired heart disease in children. In both, the inflammation can damage coronary arteries, which supply blood to the heart. These arteries can become abnormally dilated and develop aneurysms that could potentially trigger a heart attack.

Yet there are significant differences between Kawasaki disease and MIS-C. “It may be that the genetic reasons for this abnormal inflammatory response are somewhat different if the primary infection is with SARS-CoV-2 rather than whatever the primary initiating factors for classic Kawasaki disease are,” Penny explained.

In addition, Kawasaki disease often affects children five years of age and younger, while MIS-C has been diagnosed in teenagers and young adults.

Parents can take comfort in the fact that MIS-C is not common and the “risk of a child developing MIS-C is quite low,” Chang said. At the same time, he added, it’s important for parents to “stay up to date and don’t be frustrated by advice or expert opinion that changes … and understand that providers are also learning about this at the same time.”

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