This article is part of a series marking one year since the COVID-19 and pandemic began. Read more articles on the coronavirus from the Michigan Health and Michigan Health Lab blogs.

From the beginning of the pandemic, experts noticed a silver lining: children were mostly spared from getting severely sick from COVID-19.

A year later, that remains to be true with the majority of children either asymptomatic or experiencing mild illness from the virus. However, more states are also reporting cases of children developing a rare, but serious, condition called multi-system inflammatory syndrome, or MIS-C.

MIS-C causes severe inflammation in vital organs and tissues, and without treatment, could be life-threatening.

The first cases were reported in May 2020 in just a few cities in the United States and parts of Europe. But today, 48 states in the country have documented MIS-C cases.

Christine Mikesell, M.D., one of the pediatric hospitalists who helped drive MIS-C clinical guidelines at Michigan Medicine C.S. Mott Children's Hospital, answers parents' top questions about this mysterious syndrome.

SEE ALSO: Seeking Medical Care During COVID-19

What has been learned about MIS-C so far?

Mikesell: MIS-C is an extreme immune response to COVID-19 marked by shock, fever, and multi-organ inflammation. It may cause severe inflammation in the heart, lungs, blood vessels, kidneys, digestive system, brain, skin or eyes.

This condition initially appeared to only be observed in children weeks after recovering from COVID-19 and who tested positive for antibodies, but now we're also seeing cases where there's an overlap. Children have shown signs of MIS-C at the same time as testing positive for COVID-19.

At this point there are still many more questions than answers about MIS-C, including its cause and risk factors. The case numbers are so low, it's difficult to distinguish which children are at highest risk.

But several research studies, including ones my colleagues at Michigan Medicine are participating in, are studying MIS-C cases to learn more about the cause, risk factors and ways to improve diagnosis and treatment.

Has there been a rise in MIS-C cases?

Mikesell: Earlier in the pandemic, urban centers in cities like Detroit and New York were seeing the highest numbers. But recently, following surges linked to the holiday season, we've heard about upticks in states like California, Illinois and Georgia. Our sense is that this mirrors the global increase in our total numbers and is a reflection of where COVID-19 has been more active.

This is still a relatively rare condition that has occurred in two out of 100,000 children, or less than .01% of the population.

SEE ALSO: Seeking Medical Care During COVID-19

What are the health risks of MIS-C to children?

Mikesell: For parents, it can be alarming to see headlines focused on severely sick children. But this condition can be treated, and many children who develop MIS-C don't get critically ill or require intensive care. Most importantly, the majority of children who are treated for MIS-C recover entirely. 

However, there are rarer cases that have led to organ failure and death. The Centers for Disease Control has reported about 2,617 cases of MIS-C across the U.S., with a total of 33 deaths.

Long-term effects remain largely unknown, but a five-year study supported by the National Institutes of Health and National Heart, Lung, and Blood Institute is following 600 children with MIS-C throughout 2025 to track long-term outcomes. One recent study from Boston suggests that some children hospitalized with MIS-C may also show neurologic symptoms, but that they were mostly transient.  

Most children will need to follow up with a cardiologist and an infectious disease doctor to watch for potential lingering problems with coronary issues.

Who does MIS-C primarily affect?

Mikesell: This condition affects children and adolescents between ages 1 and 14, with the most common ages between 9-12. But we have also seen this in older teens and young adults in their early twenties.

More MIS-C cases are also being reported among Hispanic and Black populations. The CDC reports 66% of reported cases have occurred in children who are Hispanic or Latino (842 cases) or Black, Non-Hispanic (746 cases.) We continue to learn more, but this may be a reflection of the higher overall COVID-19 cases among these communities. 

What are the symptoms of MIS-C parents should look for?

Mikesell: Universally, all children with MIS-C have a fever for more than a day that can last two to four days, sometimes with severe flu-like symptoms. Their fever usually isn't responsive to any fever reducing medications.

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Parents should call their doctor if their child experiences this type of persistent fever and appears fatigued and ill, or has a loss of appetite.

Other symptoms vary child to child. But generally, younger children seem more likely to also experience a sunburn-like rash, bloodshot eyes, swollen hands and feet, cracked lips, a swollen tongue, congestion and swollen lymph nodes.

Adolescents and teens tend to experience more of the associated gastrointestinal symptoms, such as diarrhea, vomiting, nausea, abdominal pain, or a swollen abdomen, along with headaches and overall lethargy.

But every child is different and parents should seek medical attention if their child shows any combination of these symptoms alongside a fever. Symptoms can progress quickly.

How is MIS-C treated once diagnosed?

Mikesell: MIS-C presents itself similarly to another rare condition known as Kawasaki disease, which causes swelling in the walls of blood vessels throughout the body, increasing risk of aneurysms, blood clotting, gastrointestinal issues, kidney injury, neurologic symptoms or inflammation that hurts heart function. 

Doctors have been building on what they know about Kawasaki disease to treat MIS-C. This includes high dose aspirin, fluids and various medicines to treat inflammation. In severe cases, children may need to be treated in the pediatric intensive care unit.

We hope that more data and research will help us improve treatment options.

How have hospitals responded since the first cases of MIS-C?

Mikesell: When we first learned about MIS-C, our hospital created a task force that included experts across multiple specialties, including the emergency department, infectious diseases, immuno-hematology, cardiology and rheumatology.

This team monitored new data and studies while continuing to learn about MIS-C through colleagues at centers getting the highest case numbers and how patients were presenting in our clinics and emergency rooms.

Our goal was to develop guidelines that would help us capture all patients at risk of developing this syndrome.

We set a low threshold for any child coming in with a fever for more than 24 hours. They were monitored for MIS-C and underwent further testing when they had accompanying symptoms

Is there any way to prevent MIS-C?

Mikesell: The best protection against MIS-C is to follow recommended measures to minimize exposure to COVID-19. This includes wearing masks, frequent hand washing, social distancing and not gathering inside with people from multiple households.

What else has been learned about COVID-19 in kids?

Mikesell: Most children who get infected with SARS-CoV-2 have mild symptoms or none at all. We're still learning about why some children go on to develop more serious symptoms, like MIS-C, than others, but severe COVID-19 disease in kids is still rare.

About 1% of children with a known case of COVID-19 have been hospitalized and 0.01% have died.

Babies under age one may be at higher risk of having severe illness, according to the CDC, as well as those with some underlying medical conditions, including asthma or chronic lung disease, diabetes, genetic or neurologic conditions, sickle cell disease, congenital heart disease, obesity, a weakened immune system or medical complexity.

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