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This has been reviewed and updated as of June 21, 2020.

Multisystem Inflammatory Syndrome in Children

Perhaps the one saving grace of the coronavirus pandemic was that, for a time, the thinking was that children had largely been spared. Or, if they did get COVID-19, they were mostly asymptomatic or had mild symptoms.

While this may still be true for the vast majority of children, a new mystery illness tied to the coronavirus has recently begun affecting seemingly otherwise healthy kids.

Multisystem Inflammatory Syndrome in Children (MIS-C), also called Pediatric Multisystem Inflammatory Syndrome (PMIS) or Pediatric Inflammatory Multisystem Syndrome (PIMS), is a newly identified condition associated with COVID-19.

It can result in a persistent fever as well as inflammation that affects multiple organs, including the heart, lungs, kidneys, brain, skin, eyes, or gastrointestinal organs. COVID-19 is primarily a respiratory disease, but MIS-C affects many organs and blood vessels.

The first known published case of suspected MIS-C was reported in the journal Hospital Pediatrics in Stanford, California, in late April.

To date, children in nearly half of U.S. states have reported cases of MIS-C, though overall reported numbers are very low — only a few hundred cases across the U.S. There have also been cases reported throughout Europe. MIS-C can be serious and even deadly, but most children have gotten better with medical care, according to the U.S. Centers for Disease Control and Prevention (CDC).

While we don’t know exactly what causes MIS-C, we do know that the link to COVID-19 is pretty strong.

The vast majority of children with it have tested positive for COVID-19 or its antibodies (immunoglobulins, IgG and IgM), which indicates that MIS-C is an immune response to the virus, notes Kevin Friedman, MD, a pediatric cardiologist at Boston Children’s Hospital and assistant professor of pediatrics at Harvard Medical School. The timing of the symptoms —  which typically occur three to six weeks after acute illness — further connects the illnesses, he says.

Unlike COVID-19, however, MIS-C is not believed to be contagious.

What Happens in the Body with MIS-C?

MIS-C can be likened to other syndromes that follow an acute infection, such as Guillain-Barre syndrome that comes after influenza.

“The immune system is overreacting,” says Kwang Sik Kim, MD, professor and director of the Division of Pediatric Infectious Diseases, at John Hopkins University School of Medicine in Baltimore, Maryland, “but the mechanisms [of how and why that happens] are not completely understood.”

“Doctors are still learning about what causes MIS-C, but some children have had clinical and laboratory evidence of a phenomenon known as cytokine storm,” says Sarah Faith Taber, MD, a pediatric rheumatologist at Hospital for Special Surgery in New York City. “In cytokine storm, the normal control that the body has over the immune system is compromised, leading to an over-activation that can cause fevers, rashes, and damage to the organs.”

Who Is at Risk for Multisystem Inflammatory Syndrome in Children?

According to the CDC, the vast majority of COVID-19 cases occur in adults. Of the 1.4 million reported cases in the U.S., only 57,000 have occurred in those under age 18. And most pediatric patients who have had COVID-19 do not appear to develop MIS-C.

Experts are still trying to figure out why some kids develop MIS-C and others don’t. One theory is that it may be related to the degree of COVID-19 exposure.

It is also “likely the genetic differences in terms of the immune response to the SARS-COV2 virus,” says Dr. Friedman. In other words, some children’s bodies will fight the infection differently than other children, likely because of genetic factors.

We also don’t know yet if children with certain health conditions are more likely to get MIS-C.

“There is no evidence at this time that children with juvenile idiopathic arthritis (JIA) or other pediatric inflammatory diseases are at increased risk,” says Dr. Taber. “Recent evidence also suggests that most of the medications used to treat JIA do not place a child at increased risk of developing MIS-C or other severe manifestations of COVID.”

Healthy children with a family history of autoimmune diseases are also not at an increased risk at this time, she adds.

What Are the Symptoms of Multi-System Inflammatory Syndrome in Children?

The symptoms are similar to Kawasaki disease and toxic shock syndrome. Kawasaki disease is a rare childhood condition that causes inflammation in the walls of the arteries and can decrease blood flow to the heart. In severe cases, cardiac symptoms can develop. Toxic shock syndrome (TSS) is a cluster of symptoms caused when a toxin created by types of staphylococcus bacteria releases in the bloodstream and spreads to body organs.

Unlike Kawasaki disease, which tends to affect children under age 5, MIS-C has been found to affect healthy children of all ages, ranging from infants to teens, says Dr. Friedman. There is also a higher prevalence of gastrointestinal symptoms (abdominal pain, vomiting, diarrhea) as well as higher levels of cardiac injury biomarkers.

“Some autoimmune diseases, including systemic onset JIA and lupus, may have symptoms which are similar to MIS-C, such as fever or rash,” says Dr. Taber.

If your child develops any of the following symptoms within four weeks of coronavirus infection or after known exposure to COVID-19, contact your doctor immediately. It’s important to note, however, that not all children with MIS-C symptoms may have had obvious COVID-19 symptoms. They also may not test positive for the virus but may test positive for antibodies.

  • Kawasaki-like symptoms: rash, bloodshot eyes, swollen hands and feet, cracked lips, swollen tongue (looks like a strawberry), enlarged lymph node in the neck
  • Toxic shock-like symptoms: flu-like symptoms with high fever, sunburn-like rash, low blood pressure, high heart rate
  • Gastrointestinal symptoms: diarrhea, vomiting, abdominal pain, swollen abdomen
  • Respiratory symptoms: persistent cough and shortness of breath

According to the latest clinical guidelines from the American College of Rheumatology (ACR), MIS-C and Kawasaki disease unrelated to COVID-19 infections may share overlapping clinical features, including:

  • Conjunctival injection (red, bloodshot eyes)
  • Oropharyngeal findings (red and/or cracked lips, strawberry tongue)
  • Rash
  • Swollen and/or erythematous (red) hands and feet
  • Cervical lymphadenopathy (enlarged lymph nodes)

If your child is showing any of these emergency warning signs of MIS-C, seek emergency care right away:

  • Trouble breathing
  • Pain or pressure in the chest that does not go away
  • New confusion
  • Inability to wake or stay awake
  • Bluish lips or face
  • Severe abdominal pain

How Is Multisystem Inflammatory Syndrome in Children Diagnosed?

According to the CDC, to be diagnosed with MIS-C children must have:

  • A fever of at least 100.4 degrees for at least 24 hours
  • Evidence of inflammation in the body
  • Hospitalization with problems in at least two organs (heart, kidney, or lungs)
  • Test positive for COVID-19, antibodies, or have a known exposure to COVID-19 four weeks prior to the onset of symptoms

If MIS-C is suspected, your doctor may run the following diagnostic tests on your child to look for inflammation, blood clotting, liver function, heart function, as well as other aspects of the syndrome:

  • Blood tests
  • Chest X-ray
  • Heart ultrasound (echocardiogram)
  • Abdominal ultrasound

According to the ACR, EKGs should be performed at a minimum of every 48 hours in MIS-C patients who are hospitalized as well as during follow-up visits.

How Is Multisystem Inflammatory Syndrome in Children Treated?

Unlike COVID-19, which doesn’t yet have an established treatment regimen, MIS-C seems treatable. For some children, supportive care (antibiotics, fever reducers, fluids) may be enough, but most are admitted to the hospital and some need intensive care. Pediatric specialists in infectious disease, rheumatology, critical care, cardiology, and hematology often work together to treat different aspects of the illness. Depending on the child’s symptoms, pediatric neurologists, nephrologists, hepatologists, and gastroenterologists may also be involved in care.

The ACR recommends the following treatment for the management of MIS-C:

  • Therapeutic anticoagulation with enoxaparin (to curb blood clotting)
  • Intravenous immunoglobulin (IVIG) (for Kawasaki-like symptoms)
  • Low-moderate dose glucocorticoids (to treat respiratory symptoms)
  • High-dose, IV pulse glucocorticoids (to treat patients with life-threatening complications, such as shock)
  • Anakinra (Kineret) (for treatment of MIS-C refractory to IVIG and glucocorticoids)
  • Daily, low-dose aspirin (no more than 81 mg/day and only in children with a platelet count greater than 80,000/?)

The majority of physicians are using the first-line treatment for Kawasaki disease — intravenous immunoglobulin (IVIG) — as well as other immunomodulating therapies used in rheumatoid arthritis (RA) that suppress inflammation, says Dr. Friedman.

IVIG makes sense given that MIS-C has a lot of symptoms that overlap with Kawasaki disease, he notes, and MIS-C is a highly inflammatory disease with all these elevated inflammatory markers and cytokines.

“Steroids have also been used,” says Dr. Friedman. In fact, a recent CDC webinar noted that they were used in one-third to up to 70 percent of MIS-C cases so far.

Dr. Friedman says parents should find reassurance in the fact that this condition is rare and most children have recovered quickly. However, it is still important to know the symptoms and seek care immediately.

The bottom line for now: The information on MIS-C is still new and will continue to evolve. The best chance for keeping your kids healthy and safe is to continue to follow the CDC guidelines to keep you and your family protected from COVID-19, even as economies begin to reopen. This includes:

  • Staying home as much as possible if you have underlying health issues
  • Washing hands with soap and water for at least 20 seconds
  • Following social distancing when near anyone who is not in your own household
  • Wearing a cloth face mask in public areas (if the child is over age 2)
  • Disinfecting frequently touched surfaces
  • Staying up to date on your child’s vaccines

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Clinical Guidance for Pediatric Patients with Multisystem Inflammatory Syndrome in Children (MIS-C) Associated with SARS-CoV-2 and Hyperinflammation in COVID-19. American College of Rheumatology. June 17, 2020. https://www.rheumatology.org/Portals/0/Files/ACR-COVID-19-Clinical-Guidance-Summary-MIS-C-Hyperinflammation.pdf.

For Parents: Multisystem Inflammatory Syndrome in Children (MIS-C) associated with COVID-19. Coronavirus Disease 2019 (COVID-19). U.S. Centers for Disease Control and Prevention. May 20, 2020. https://www.cdc.gov/coronavirus/2019-ncov/daily-life-coping/children/mis-c.html.

Interview with Kevin Friedman, MD, a pediatric cardiologist at Boston Children’s Hospital and assistant professor of pediatrics at Harvard Medical School

Interview with Kwang Sik Kim, MD, professor and director of the Division of Pediatric Infectious Diseases, at John Hopkins University School of Medicine in Baltimore, Maryland

Interview with Sarah Faith Taber, MD, a pediatric rheumatologist at Hospital for Special Surgery in New York City

Jones VG, et al. COVID-19 and Kawasaki Disease: Novel Virus and Novel Case. Hospital Pediatrics. June 2020. doi: https://doi.org/10.1542/hpeds.2020-0123.

Kawasaki Disease. National Organization for Rare Disorders. https://rarediseases.org/rare-diseases/kawasaki-disease.

Multisystem Inflammatory Syndrome in Children (MIS-C). Boston Children’s Hospital. http://www.childrenshospital.org/conditions-and-treatments/conditions/m/mis-c.

Multisystem Inflammatory Syndrome in Children (MIS-C) Associated with Coronavirus Disease 2019 (COVID-19). Emergency Preparedness and Response. U.S. Centers for Disease Control and Prevention. May 19, 2020. https://emergency.cdc.gov/coca/calls/2020/callinfo_051920.asp.