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November 10, 2021

What is MIS-C—and Should Parents Be Worried?

What is MIS-C—and Should Parents Be Worried?

Evidence is growing that COVID-19 vaccination for school-aged children is safe and effective. This positive news is more important than ever as cases among kids are on the rise, and U.S. health officials have reported an uptick in rare but serious COVID-related complications among young people.  

As of October 14, nearly 6.2 million children in the United States have tested positive for COVID-19, according to a report from the American Academy of Pediatrics and the Children’s Hospital Association. Overall, children have accounted for an average of 16.4 percent of all COVID cases but, in recent weeks, that proportion has risen to 1 in 4 reported cases due to the rise of the more contagious Delta variant.

Kids are more likely to develop mild infections, but there have been more than 8,600 hospitalizations through mid-September among children between 5 and 11-years old. And though it is uncommon, some infected kids do develop complications.

One particularly worrisome COVID-19-related complication affecting young people is a condition called multisystem inflammatory syndrome in children, or MIS-C.

Reported cases on the rise
In May, former U.S. Food and Drug Administration commissioner Scott Gottlieb, MD, warned about a link between coronavirus infection and this dangerous new inflammatory disorder in children. By the end of June, doctors from several countries had reported about 1,000 cases of MIS-C. 

As of October 4, 2021, the CDC has received reports of 5,217 confirmed cases of MIS-C and 46 deaths in 49 states, New York City, and Washington, DC. Additional cases are also under investigation. The CDC reports a roughly 15 percent uptick in cases between late July and early October.

Most of these cases involved children between 1 and 14-years old but MIS-C has been diagnosed in younger children and adults up to 20-years old. The CDC reports that more than 60 percent of reported MIS-C cases have occurred in children who are Black or Hispanic/Latino. More than 98 percent of cases tested positive for COVID-19 while the remaining 2 percent were exposed to someone with the disease. In most cases, children developed MIS-C between two and four weeks after being infected with the coronavirus. 

A July 2020 study published in the New England Journal of Medicine (NEJM) investigated 186 cases of MIS-C associated with COVID-19 in 26 different states. Researchers found that many of the young people affected were otherwise healthy children and teens. Of these cases, four were fatal. A separate July 2020 study in NEJM included 95 confirmed cases in New York State. Of these cases, two were fatal.

“Up until this, a lot of people, myself included, were kind of reassured by the fact that children didn’t seem to be as severely affected” by COVID-19 compared to adults, says Cara Haberman, MD, a pediatric hospital medicine specialist at Wake Forest Baptist Health in Winston-Salem, North Carolina. “We didn’t get off as easy as we thought—there is this pretty scary and severe illness. It’s rare, but it exists, and we have to worry about it.”

What is MIS-C and what are the warning signs?
Like its name implies, multisystem inflammatory syndrome in children is a condition associated with inflammation in at least two different parts of the body—the heart, lungs, kidneys, brain, skin, eyes or organs of the digestive system.

MIS-C typically begins with fever—often 3 to 5 days of a persistently high temperature, Dr. Haberman explains.

In addition, children with early MIS-C often show gastrointestinal warning signs, including belly pain, vomiting and diarrhea. Rash is common. Children may also develop sleepiness, confusion or headaches. Red eyes and swollen lymph nodes are other possible symptoms. Some of these signs of MIS-C could be confused with more benign childhood illnesses.

So, how can parents distinguish between routine childhood fevers or bellyaches and much more serious issues?

“That’s what’s been really hard,” Haberman admits. “You see kids with fever and vomiting all the time. How would you know to worry?”

Call your doctor right away if your child has had COVID-19 or exposure to someone with COVID-19 within the past 6 weeks, plus a fever of 100.4 degrees or higher that lasts more than 24 hours, plus more than one of the following:

  • Dizziness or lightheadedness
  • Skin rash
  • Belly pain
  • Vomiting
  • Diarrhea
  • Red eyes

“Any time parents are concerned about high fevers or any of these sorts of symptoms, they should bring it up to their physician as soon as they can and make sure that they mention if there’s been an exposure to COVID, or a potential exposure,” says Kacy Ramirez, MD, a pediatric infectious-diseases specialist at Wake Forest Baptist Health.

Keep in mind the following warning signs of a medical emergency that require immediate attention:

  • Trouble breathing
  • Pale, gray, or bluish skin, lips, or nail beds
  • Confusion or unusual behavior
  • Drowsiness or trouble waking
  • Severe belly pain
  • Chest pain or pressure that does not go away

If your child develops one or more of these serious symptoms, call 911 or go to the emergency room right away.

So does COVID-19 cause MIS-C?
Probably, but we’re not certain. Doctors do not yet know exactly what causes MIS-C. It can take time to establish that a particular pathogen causes a disease, and researchers are being careful not to state categorically yet that infection with the SARS-CoV-2 virus causes MIS-C.

That said, there is strong evidence linking the two. Many children with MIS-C have a history of recent COVID-19 or of a likely exposure, and most carry the telltale antibodies that mark a recent infection with the coronavirus. Most, however, do not show current evidence of infection.

“What we understand about it is that it’s probably a spectrum of COVID-related disease with severe inflammation,” says Dr. Ramirez. “It’s probably an inflammatory response to the virus.”

How MIS-C is diagnosed
In order to diagnose MIS-C, doctors need to rule out other possible causes. Children must also test positive for COVID-19, have antibodies to the coronavirus (which would indicate that they were infected in the past and recovered) or have a history of exposure to an infected person within 4 weeks of when their symptoms started.

In most cases, children with MIS-C have antibodies to the coronavirus and are not currently infected.

It can be confusing, Haberman says, because some children develop MIS-C symptoms without having originally had obvious signs of COVID-19 in the first place. They may have mild or no COVID-19 symptoms but then develop this overreaction of the immune system 2 to 4 weeks later, she explains.

In the United States, Hispanic/Latino and Black children are disproportionately affected by MIS-C, accounting for a combined 61 percent of cases as of October 14. This could reflect structural health disparities, differences in genetic susceptibility, or the fact that COVID-19 is more common in these communities.

Wake Forest pediatricians developed an algorithm to help colleagues decide when a child with fever should undergo outpatient testing to check for MIS-C. Laboratory tests can pick up telltale inflammatory markers and cell patterns. Among the possible signs of MIS-C:

  • Elevated C-reactive protein (CRP): Levels of this substance produced by the liver may be higher than normal when there is inflammation in the body.
  • Elevated erythrocyte sedimentation rate (ESR): This blood test measures how quickly red blood cells settle at the bottom of a test tube. A faster-than-normal rate may signal inflammation in the body.
  • Low levels of lymphocytes (a type of white blood cell) and/or platelets (cells that circulate in the blood, which are involved in clotting).

“We check them and then we trend them for a day or two, make sure that they’re headed in the right direction. As long as they are, that’s really reassuring,” Haberman notes.

Definitive diagnosis depends on the whole picture—the child’s symptoms and signs, history, bloodwork and possibly tests, such as electrocardiograms, echocardiograms, X-rays or CT scans.

Ruling out other possible issues
Some adults with COVID-19 experience a potentially deadly inflammatory response known as a cytokine storm. But this typically strikes in the second week of illness—not a month later, as is more often the case with MIS-C.

“Adults don’t seem to have this lag period where they are asymptomatic in between. Why this is the case is still very unclear,” Haberman says.

MIS-C can also resemble other inflammatory syndromes, including Kawasaki disease (KD). Both MIS-C and KD can, for instance, result in heart problems, lesions of the skin and mucous membranes and central nervous system disturbances.

Still, there are important differences. KD typically strikes toddlers, whereas the most recent CDC data indicates that children with MIS-C are, on average, 9 years old.

Children with MIS-C are also more likely than those with KD to be in shock when they seek medical care, according to the American College of Rheumatology. Levels of CRP also tend to be higher in children with MIS-C compared to children diagnosed with KD, and their blood counts differ in important ways.

These two conditions may also affect the heart—but in different ways. Still, enough patients have features of both that the two inflammatory diseases may shed light on each other, Haberman points out.

“Finding out some more answers about MIS-C may answer some questions about Kawasaki disease and what types of viruses are associated with that illness,” she explains.

How MIS-C is treated
Most children diagnosed with MIS-C are sick enough to be hospitalized, according to Ramirez.

Because the disease can strike so many organ systems, treatment typically requires a team of medical professionals. The American College of Rheumatology recommends involving children’s doctors specially trained to treat inflammatory problems, heart problems, infections, and blood diseases. Experts in diseases of the brain and nerves, kidneys, liver, or digestive system in children may also help.

In addition to supportive measures, such as intravenous (IV) fluids, treatment typically includes intravenous immunoglobulin (a drug that contains antibodies), steroids, antibiotics, treatments for clotting, and, in some cases, anti-inflammatory drugs ordinarily used to treat autoimmune disease. This regimen may also successfully treat kids with KD. But the ideal treatment is still unknown, Ramirez says.

Most children with MIS-C get better over time, but we still know very little so far about the long-term consequences of MIS-C. In the NEJM study, the average hospital stay lasted about a week, while a study of 46 children in England found that by the 6-month mark, most physical abnormalities had recovered. But the researchers also detected lingering problems with fitness and emotional health in some of the children.

Protecting your child
Protection against MIS-C can be summed up as follows: Vaccinate and take all other precautions for protection against COVID-19.

The Pfizer COVID vaccine is already FDA-approved for use in people ages 16-years and older and is available under emergency use authorization (EUA) for kids and teens between 12 and 15-years old. U.S. regulatory officials are in the process of reviewing evidence to determine if the vaccine is also safe and effective for kids between 5 and 11-years old. The vaccine could be available for kids in this younger age group by early November.

And remember, MIS-C is rare. For the kids who are affected, the sooner they receive treatment, the better. Most children are able to recover if they are diagnosed and treated early on.

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