Multisystem Inflammatory Syndrome in Children (MIS-C)  Information for Healthcare Professionals

Summary  

In April of 2020, clinicians in the United Kingdom recognized the presence of severe inflammatory syndrome in otherwise healthy children who currently or recently tested positive for SARS-CoV-2, the virus that causes COVID-19. These patients presented with systemic signs and symptoms such as fever, hypotension, and multiorgan system involvement. Since May 2020, the Centers for Disease Control and Prevention (CDC) has requested reports of multisystem inflammatory syndrome in children (MIS-C). MIS-C is reportable in Georgia, and suspect cases should be reported to the Georgia Department of Public Health (DPH). 

 For more information on the number of MIS-C cases in the US and Georgia please visit https://dph.georgia.gov/mis-c-statistics   

Reporting  

Reporting information for Medical Examiners and Coroners  

Report suspect deaths to the Georgia Department of Public Health as soon as possible.   

  • Report cases electronically through the State Electronic Notifiable Disease Surveillance System (SendSS): https://sendss.state.ga.us/ords/sendss/login.screen    
  • Alternatively, providers may report by phone to their local health district office or by calling 404-657-2588 during business hours or 1-866-PUB-HLTH evenings and weekends.   

Case Definition

As of January 1, 2023, the CSTE/CDC  MIS-C case definition is:

Any illness in a person aged less than 21 years that meets:

  • The clinical AND the laboratory criteria (Confirmed), OR
  • The clinical criteria AND epidemiologic linkage criteria (Probable), OR
  • The vital records criteria (Suspect)

 

Clinical Criteria

Laboratory Criteria for SARS-CoV-2 Infection

Epidemiologic Linkage Criteria

Vital Records Criteria

An illness characterized by all of the following, in the absence of a more likely alternative diagnosis*

  • Subjective or documented fever (temperature ≥38.0⁰ C)
  • Clinical severity requiring hospitalization or resulting in death
  • Evidence of systemic inflammation indicated by C-reactive protein ≥3.0 mg/dL (30 mg/L)
  • New onset manifestations in at least two of the following categories:
    1. Cardiac involvement indicated by:
      • Left ventricular ejection fraction <55% OR
      • Coronary artery dilatation, aneurysm, or ectasia, OR
      • Troponin elevated above laboratory normal range, or indicated as elevated in a clinical note
    2. Mucocutaneous involvement indicated by:
      • Rash, OR
      • Inflammation of the oral mucosa (e.g., mucosal erythema or swelling, drying, or fissuring of the lips, strawberry tongue), OR
      • Conjunctivitis or conjunctival injection (redness of the eyes), OR
      • Extremity findings (e.g., erythema [redness] or edema [swelling] of the hands or feet)
    3. Shock**
    4. Gastrointestinal involvement indicated by:
      • Abdominal pain, OR
      • Vomiting, OR
      • Diarrhea
    5. Hematologic involvement indicated by:
      • Platelet count <150,000 cells/μL, OR
      • Absolute lymphocyte count (ALC) <1,000 cells/μL

 
  • Detection of SARS-CoV-2 RNA in a clinical specimen*** up to 60 days prior to or during hospitalization, or in a post-mortem specimen using a diagnostic molecular amplification test (e.g., polymerase chain reaction [PCR]), OR
  • Detection of SARS-CoV-2 specific antigen in a clinical specimen*** up to 60 days prior to or during hospitalization, or in a post-mortem specimen, OR
  • Detection of SARS-CoV-2 specific antibodies^ in serum, plasma, or whole blood associated with current illness resulting in or during hospitalization

 

Close contact‡ with a confirmed or probable case of COVID-19 disease in the 60 days prior to hospitalization

A person whose death certificate lists MIS-C or multisystem inflammatory syndrome as an underlying cause of death or a significant condition contributing to death

 

*If documented by the clinical treatment team, a final diagnosis of Kawasaki Disease should be considered an alternative diagnosis. These cases should not be reported to national MIS-C surveillance.

** Clinician documentation of shock meets this criterion.

***Positive molecular or antigen results from self-administered testing using over-the-counter test kits meet laboratory criteria.

^Includes a positive serology test regardless of COVID-19 vaccination status. Detection of anti-nucleocapsid antibody is indicative of SARS-CoV-2 infection, while anti-spike protein antibody may be induced either by COVID-19 vaccination or by SARS-CoV-2 infection.

‡Close contact is generally defined as being within 6 feet for at least 15 minutes (cumulative over a 24-hour period). However, it depends on the exposure level and setting; for example, in the setting of an aerosol-generating procedure in healthcare settings without proper personal protective equipment (PPE), this may be defined as any duration.

     

Disease Presentation  

MIS-C can occur weeks after SARS-CoV-2 infection. The child may have been infected by an asymptomatic contact, and in some cases the child or family may not be aware that they had been infected.    

Patients with MIS-C usually present with fever, abdominal pain, vomiting, diarrhea, skin rash, mucocutaneous lesions and, in severe cases, with hypotension and shock.  They also have elevated laboratory markers of inflammation (e.g., CRP, ferritin), a majority have laboratory markers indicating damage to the heart (e.g., elevated troponin), and many have low absolute lymphocyte counts (lymphopenia). Some patients develop cardiac dysfunction; gastrointestinal inflammation (e.g., abdominal pain, vomiting, and diarrhea) and some may have signs and symptoms similar to those of acute appendicitis. Neck pain has also been described, sometimes with development of phlegmon on radiographic imaging. Children with MIS-C can present with neurologic involvement which is usually transient in the form of headache or altered mental status. Children with MIS-C can develop severe neurologic manifestations including severe encephalopathy and stroke.

 

Clinical Recommendations  

Early medical care, as well as pediatric infectious disease, cardiology, and rheumatology referrals may be warranted. Any suspect MIS-C case should be cared for in a hospital with tertiary pediatric/cardiac intensive care units. 

Given the frequent association of MIS-C with cardiac involvement, many centers are performing cardiac testing including, but not limited to:  

  • echocardiogram;  
  • electrocardiogram;  
  • cardiac enzyme or troponin testing (per the center’s testing standards); and  
  • B-type natriuretic peptide (BNP) or NT-proBNP.  

Other testing to evaluate multisystem involvement should be directed by patient signs or symptoms. Additionally, testing to evaluate for other potential diagnoses should be directed by patient signs or symptoms. Visit the Centers for Disease Control and Prevention (CDC) MIS-C webpage for more information: https://www.cdc.gov/mis/hcp/index.html  

Laboratory Testing  

  • Testing aimed at identifying laboratory evidence of inflammation as listed in the Case Definition section is warranted.  
    •  SARS-CoV-2 detection by RT-PCR or antigen test is indicated.  
    •  SARS-CoV-2 serologic testing is suggested, even in the presence of positive results from RT-PCR or antigen testing.  
  • Any serologic testing should be performed prior to administering intravenous immunoglobulin (IVIG) or any other exogenous antibody treatments.  
  • Additional information on SARS-CoV-2 can be found here: https://dph.georgia.gov/covidtesting 

Treatment  

At this time, there have been no studies comparing clinical efficacy of various treatment options.  Treatments have consisted primarily of supportive care and directed care against the underlying inflammatory process.  Supportive measures have included fluid resuscitation, inotropic support, respiratory support, and  extracorporeal membranous oxygenation (ECMO) in rare cases. 

Anti-inflammatory measures have included the frequent use of IVIG and steroids. The use of other anti-inflammatory medications and the use of anti-coagulation treatments have been variable. Aspirin has commonly been used due to concerns for coronary artery involvement, and antibiotics are routinely used to treat potential sepsis while awaiting bacterial cultures. Thrombotic prophylaxis is often used given the hypercoagulable state typically associated with MIS-C.  

Visit the Centers for Disease Control and Prevention (CDC) MIS-C webpage for more information: https://www.cdc.gov/mis/hcp/index.html 

Follow up  

Patients with a diagnosis of MIS-C should have close outpatient follow-up, including pediatric cardiology follow-up starting 2 to 3 weeks after discharge.  

Additional Resources 

References  

Page last updated 1/11/23