Multisystem Inflammatory Syndrome in children (MIS-C) and COVID-19: What providers should know

Multisystem inflammatory syndrome in children, or MIS-C, is a new syndrome that has been reported worldwide in an increasing number of children who had or were exposed to COVID-19. MIS-C shares many characteristics with Kawasaki disease, an inflammatory disease of childhood that can affect blood vessels.

This Q & A with Dr. Negar Ashouri, a pediatric infectious disease specialist at CHOC Children’s, explores what providers should know about MIS-C, including recently released guidance from the American Academy of Pediatrics.

What is MIS-C?

MIS-C is a rare complication temporally associated with COVID-19. Here is the case definition, per a U.S. Centers for Disease Control Health Advisory:

  • An individual aged <21 years presenting with fever (>38.0°C for ≥24 hours, or report of subjective fever lasting ≥24 hours); laboratory evidence of inflammation (Including, but not limited to, one or more of the following: an elevated C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), fibrinogen, procalcitonin, D-dimer, ferritin, lactic acid dehydrogenase (LDH), or interleukin 6 (IL-6), elevated neutrophils, reduced lymphocytes and low albumin.); and evidence of clinically severe illness requiring hospitalization, with multisystem (≥2) organ involvement (cardiac, renal, respiratory, hematologic, gastrointestinal, dermatologic, or neurological); AND
  • No alternative plausible diagnoses; AND
  • Positive for current or recent SARS-CoV-2 (COVID-19) infection by RT-PCR, serology, or antigen test; or COVID-19 exposure within the four weeks prior to the onset of symptoms.

Is MIS-C dangerous?

MIS-C can be serious, but most children have recovered. MIS-C, like Kawasaki disease, can be a very uncomfortable illness because it causes prolonged fever, irritation and inflammation in many tissues of the body. The main concern with MIS-C and Kawasaki disease is heart and blood vessel involvement.

Conditions that involve inflammation in the heart, such as MIS-C or Kawasaki disease, can affect the heart in different ways. They may cause the heart muscle to be irritated and inflamed, affecting the overall function of the heart.

They may also weaken the wall of one or more of the coronary arteries causing them to bulge or balloon out. Blood clots can form in the ballooned area and possibly block the blood flow through the coronary artery. When this happens, the heart muscle will no longer receive an adequate supply of oxygen-rich blood, and the heart muscle can be damaged.

Dr. Negar Ashouri, pediatric infectious disease specialist, CHOC Children’s

What are the symptoms of MIS-C?

Though clinicians have described differing presentations, sign and symptoms can include an ongoing fever, inflammation detected by blood test, and evidence of organ dysfunction or shock. Here are additional common symptoms:

  • Kawasaki disease-like features including conjunctivitis; red eyes; red or swollen hands and feet; rash; red cracked lips; and swollen glands. Some children have presented with coronary artery enlargement or aneurysms. Some children may present with  more gastrointestinal (abdominal pain or diarrhea) or neurologic (headaches/meningitis) manifestations.
  • Toxic shock syndrome-like features with hemodynamic instability.
  • Cytokine storm/macrophage activation or hyperinflammatory features.
  • Shortness of breath suggestive of congestive heart failure.
  • Respiratory symptoms typically reported in adults with COVID-19 may not be present in pediatric patients with MIS-C.

Patients with the following symptoms ought to seek emergency care:

  • Persistent fevers
  • 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 MIS-C diagnosed?

Children who present with symptoms may undergo expanded laboratory testing and a cardiac workup that may include:

  • Routine screening labs including CBC with diff, CRP, CMP, and appropriate cultures;
  • If expanded work-up is warranted for hospitalized patients, it may include  troponin, pro-B-type natriuretic peptide, triglycerides, creatine kinase, ,  D-dimer, prothrombin time/partial thromboplastin time, international normalized ratio,  ferritin, lactic acid dehydrogenase,  and fibrinogen, if not already conducted;
  • COVID-19 testing performed with RT-PCR assay and serologic testing in every case;
  • echocardiogram;
  • electrocardiogram;
  • chest X-ray; and
  • abdominal ultrasound.

When should a provider suspect MIS-C?

Per the AAP, any child with suspected MIS-C should also be evaluated for infectious and noninfectious etiologies.

An initial sign may be a persistent fever without a clear clinical source. Providers should be suspicious of any fever accompanied by symptoms concerning in their severity or coincident with recent exposure to COVID-19.

Some children clinically progress rapidly and may develop hemodynamic compromise. These children should be followed and cared for in a hospital with tertiary pediatric/cardiac intensive care units.


How is MIS-C treated?

Kawasaki and MIS-C are best treated in the hospital by a qualified multidisciplinary group of pediatric specialists who will work to reduce inflammation and minimize long-term heart damage.

Here is the APP guidance for treatment:

  • Some patients with MIS-C have been treated with IVIG, Occasionally,  Patients have also been treated with steroid therapy  and or biologics that may require taper of the medications overtime.
  • Given the need for early intervention and the need to initiate treatment for multiple possible etiologies, many patients have received concurrent antibiotic therapy.
  • A multidisciplinary group is generally involved which may include Infectious disease specialists, cardiologists, intensivists, hospitalists and rheumatologists.

What is the follow-up for patients with MIS-C?

Children who have had serious cases of MIS-C should have close outpatient follow-up care by a group of specialists which may include cardiology, hematology and infectious diseases.

Refer a patient to the infectious disease team at CHOC Children’s.