Information for Healthcare Providers about Multisystem Inflammatory Syndrome in Children (MIS-C)
The American Academy of Pediatrics has published interim guidanceexternal icon on multisystem inflammatory syndrome in children (MIS-C).
Case Definition for MIS-C
As described in the CDC Health Advisory, “Multisystem Inflammatory Syndrome in Children (MIS-C) Associated with Coronavirus Disease 2019 (COVID-19),” the case definition for MIS-C is:
- An individual aged <21 years presenting with fever*, laboratory evidence of inflammation**, 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 infection by RT-PCR, serology, or antigen test; or exposure to a suspected or confirmed COVID-19 case within the 4 weeks prior to the onset of symptoms.
*Fever >38.0°C for ≥24 hours, or report of subjective fever lasting ≥24 hours
**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
- Some individuals may fulfill full or partial criteria for Kawasaki disease but should be reported if they meet the case definition for MIS-C.
- Consider MIS-C in any pediatric death with evidence of SARS-CoV-2 infection.
Patients with MIS-C usually present with persistent fever, abdominal pain, vomiting, diarrhea, skin rash, mucocutaneous lesions and, in severe cases, with hypotension and shock. They have elevated laboratory markers of inflammation (e.g., CRP, ferritin), and in a majority of patients laboratory markers of damage to the heart (e.g., troponin; B-type natriuretic peptide (BNP) or proBNP). Some patients develop myocarditis, cardiac dysfunction, and acute kidney injury. Not all children will have the same signs and symptoms, and some children may have symptoms not listed here. MIS-C may begin weeks after a child is infected with SARS-CoV-2. The child may have been infected from an asymptomatic contact and, in some cases, the child and their caregivers may not even know they had been infected.
- Testing aimed at identifying laboratory evidence of inflammation as listed in the Case Definition section is warranted.
- Similarly, SARS-CoV-2 detection by RT-PCR or antigen test is indicated.
- Where feasible, 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.
Given the frequent association of MIS-C with cardiac involvement, many centers are performing[1-3] cardiac testing including, but not limited to:
- 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.
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
- in rare cases, extracorporeal membranous oxygenation (ECMO).
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.
The American College of Rheumatology has developed clinical guidanceexternal icon for pediatric patients diagnosed with MIS-C associated with SARS-CoV-2.
According to guidelines from the American Academy of Pediatricspdf iconexternal icon, the following ICD-10-CM diagnosis codes should be used for a child admitted to the hospital due to documented MIS-C.
U07.1, COVID-19 (principal diagnosis) and M35.8, other specified systemic involvement of connective tissue (secondary diagnosis).
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.
For more information, see AAP Interim Guidance on Multisystem Inflammatory Syndrome in Children (MIS-C)external icon.
Healthcare providers should report suspected cases among patients younger than 21 years of age meeting MIS-C criteria described in the case definition above to their local, state, or territorial health department. Clinicians can report by submitting either completed case report forms or medical records for review to their state, local, or territorial health department. After-hours phone numbers for health departments are available at the Council of State and Territorial Epidemiologists websiteexternal icon. For additional reporting questions, please contact CDC’s 24-hour Emergency Operations Center at 770-488-7100.
Case Report Form
- Instructions for Multisystem Inflammatory Syndrome Associated with COVID-19 Case Report Form pdf icon[164 KB, 5 pages]
- Fillable Multisystem Inflammatory Syndrome Associated with COVID-19 Case Report Form pdf icon[411 KB, 3 pages]
- Printable Multisystem Inflammatory Syndrome Associated with COVID-19 Case Report Form pdf icon[119 KB, 3 pages]
- Belhadjer Z, Meot M, Bajolle F, et al. Acute heart failure in multisystem inflammatory syndrome in children (MIS-C) in the context of global SARS-CoV-2 pandemicexternal icon. Circulation 2020.
- Riphagen S, Gomez X, Gonzalez-Martinez C, Wilkinson N, Theocharis P. Hyperinflammatory shock in children during COVID-19 pandemicexternal icon. Lancet 2020.
- Verdoni L, Mazza A, Gervasoni A, et al. An outbreak of severe Kawasaki-like disease at the Italian epicentre of the SARS-CoV-2 epidemic: an observational cohort studyexternal icon. Lancet 2020.
- American Academy of Pediatrics: Codingexternal icon
- American Academy of Pediatrics: Multisystem Inflammatory Syndrome in Children (MIS-C) Interim Guidanceexternal icon
- American College of Rheumatology: Clinical Guidance for Pediatric Patients with Multisystem Inflammatory Syndrome in Children (MIS-C) Associated with SARS-CoV-2 and Hyperinflammation in COVID-19pdf iconexternal icon
- Clinical Outreach and Communication Activity (COCA) Webinar, May 19, 2020: Multisystem Inflammatory Syndrome in Children (MIS-C) Associated with Coronavirus Disease 2019 (COVID-19)
- CDC Health Advisory (5/14/20): Multisystem Inflammatory Syndrome in Children (MIS-C) Associated with Coronavirus Disease 2019 (COVID-19)
- COVID-19 Information for Pediatric Healthcare Providers
- Clinical Questions about COVID-19: Questions and Answers
- Interim Clinical Guidance for Management of Patients with Confirmed Coronavirus Disease (COVID-19)
- Kawasaki Disease
- Multisystem Inflammatory Syndrome in Children: Survey of Early Hospital Evaluation and Managementexternal icon
- For Parents: Multisystem Inflammatory Syndrome in Children (MIS-C)