What is Multisystem Inflammatory Syndrome in Children (MIS-C)?

As of February 8th, 2021, a total of two thousand and sixty children have been reported as suffering from MIS-C. Thirty have died from it.

When COVID-19 made its debut as an emerging pathogen, coming to the front doors of American homes–no longer the far-off threat that it appeared in December 2019–the first data seemed to indicate one silver lining among the chaos the world was seeing.

Children seemed to be near-immune to the virus.

CNBC reported on February 11, 2020: “The coronavirus seems to be sparing one group of people–kids”. It was believed children perhaps developed asymptomatic or extremely mild cases, while increased age was directly correlated with a higher risk of illness and death. The decision to close schools was left up to each individual district.

But on March 16th, the first cases of a new threat began to crop up in the United States. Its symptom set was not that of the waking COVID-19 pandemic. These children had a new type of disease, and 99% of children shown to develop this new condition tested positive for COVID-19. This was a secondary emerging illness, caused by SARS-CoV-2 viral infection, and it occurred only in pediatric patients.

Children were being admitted to the emergency room with severely irritated red eyes, sweating with uncontrollable fevers, their hands and feet swollen, unresponsive to over-the-counter medicine. Abdominal pain kept them awake, caused by severe gastrointestinal inflammation. Their blood pressures were dropped drastically, bodies covered in dry rashes, with inflammation spreading to the critical cardiovascular system. Their blood samples were full of inflammatory markers. Some of these children, with a median age of eight years old, were dying of cardiovascular dysfunction. Virtually all tested positive for COVID-19. This condition would come to be known as multisystem inflammatory syndrome in children, or MIS-C.

Doctors did not know what this disease was, but it was quickly linked with another mysterious pediatric disorder. Now introducing another piece of the puzzle: Kawasaki disease.

Kawasaki disease is a condition without a clear pathology, but it presents symptoms very much like that of MIS-C. Kawasaki and MIS-C have striking similarities: both occurring in children aged under 10, causing high fever, abdominal pain, peripheral swelling, and lymphedema. Kawasaki, like MIS-C, puts patients at risk for heart dysfunction. However, each disease affects the function of the heart in a distinct way. This article delineates the exact differences between cardiac features of Kawasaki and MIS-C.

Nobody knows exactly what causes Kawasaki disease, but theories rage from an overly-robust immune response to environmental factors. But for some reason, only children are susceptible to this potentially deadly, pathologically mysterious inflammatory illness.

Similarly, MIS-C is of unknown origin. But the correlation to COVID-19 is undeniable. 99% test positive for COVID-19 or antibodies, and the 1% who don’t have been exposed to a case closely.

In the interest of clarity, the exact symptoms checklist leading to diagnosis of MISC are listed below:

1. The patient is under 10 years old.
2. The patient presents with a fever lasting more than 3 days.
3. At least two of the following accompanying symptoms: (a) rash, OR conjunctivitis in both eyes without the presence of pus, OR inflammation of the skin and membranes; (b) low blood pressure or shock; (c) features of cardiovascular dysfunction; (d) impairment of the blood’s ability to clot; (e) diarrhea, vomiting, or abdominal pain.
4. Presence of inflammatory markers in blood samples (such as erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), or procalcitonin).
5. Exclusion of a microbial cause of inflammation, and
6. Evidence of COVID-19 infection.

Inflammatory issues across multiple organ systems are represented in this checklist: gastrointestinal, cardiovascular, and general peripheral edema. Many also experience some of the respiratory symptoms associated in primary COVID-19 infections, with a pediatric patient in one case study even receiving mechanical ventilation after experiencing fluid buildup in the lungs while simultaneously receiving treatment in the cardiac intensive care unit.

The mystery of MIS-C is far from being unraveled, and interestingly, months after the first cases of MIS-C were reported, a similar, much more rare condition was reported in some adults: multisystem inflammatory syndrome in adults (MIS-A). However, only a handful of MIS-A cases have been reported, unlike the thousands of MIS-C cases reported by the CDC. Nobody knows what causes this multisystem inflammatory response. But what we do know is that it has the potential to be fatal.

One study examined 186 MIS-C patients in 26 different states. Of these 186 pediatric patients, two percent died from the condition. The overall death rate as of February 2021 as reported by the CDC is a bit lower, coming in at approximately 1.5% of patients dying from MIS-C. These are children with a median age of eight years old.

The original idea that children rarely develop severe cases of primary COVID-19, and even more rarely die from it, is true. Only 0.05% of pediatric COVID-19 patients die from the illness, with only 1.2% of pediatric cases resulting in hospitalization. That puts the mortality rate of MIS-C at 30% higher for children than primary COVID-19 infection.

Though the underlying cause of the condition (apart from the clear correlation with COVID-19 exposure and infection) remains an absolute mystery, many parents remain complacent about their children’s exposures. Though children represent an extremely low percentage of total primary COVID-19 infections, parents must remain vigilant in protecting their kids from unnecessary exposures in schools, grocery stores, or day-cares. MIS-C is potentially lethal, and some children experience lingering cardiac issues even after recovery from this condition.

A year after February 2020, the science has shown kids are not as safe as originally thought from this virus. The potential for them to get really sick is undeniable. However, a lack of awareness and media coverage keeps many people unaware of MIS-C at all, let alone its dire risks to young children. It is essential that parents should be equally vigilant about their children’s COVID-19 exposures as their own, using masks, handwashing, and social distancing liberally.