Case Definitions and Reporting

Key points

The Council of State and Territorial Epidemiologists (CSTE) and ÐÇ¿ÕÓéÀÖ¹ÙÍø developed an updated standardized surveillance case definition for multisystem inflammatory syndrome in children (MIS-C) associated with SARS-CoV-2 infection, effective January 1, 2023. The CSTE/ÐÇ¿ÕÓéÀÖ¹ÙÍø MIS-C surveillance case definition establishes clinical, laboratory, and epidemiological reporting criteria to identify cases as confirmed, probable, or suspect.

Three health care providers discussing clinical interventions in a hospital setting

MIS-C Case Definition

As described in the Council for State and Territorial Epidemiologists' (CSTE) position statement, "" the CSTE/ÐÇ¿ÕÓéÀÖ¹ÙÍø case definition for MIS-C is as follows:

Any illness in a person <21 years of age 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 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)
  • 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.

MIS-A Case Definition

The Centers for Disease Control and Prevention defines Multisystem Inflammatory Syndrome in Adults (MIS-A) as an illness in in a person ≥ 21 years of age with:

  • Hospitalization for ≥ 24 hours* AND
  • Subjective of documented fever (≥38.0 C) for ≥24 hours prior to hospitalization or within the first THREE days of hospitalization AND
  • An illness meeting the following clinical and laboratory criteria:
Clinical Criteria Laboratory Criteria
No alternative diagnosis (e.g. bacterial sepsis, exacerbation of a chronic medical condition) AND
At least THREE of the following clinical criteria occurring prior to hospitalization or within the first THREE days of hospitalization. At least ONE must be a primary clinical criterion.
Primary clinical criteria
  • Severe cardiac illness** (Includes myocarditis, pericarditis, coronary artery dilatation/aneurysm, new-onset right or left ventricular dysfunction (LVEF<50%), 2nd/3rd degree A-V block, or ventricular tachycardia.)
  • Rash AND non-purulent conjunctivitis

Secondary clinical criteria

  • New-onset neurologic signs and symptoms (Includes encephalopathy in a patient without prior cognitive impairment, seizures, meningeal signs, or peripheral neuropathy including Guillain-Barré syndrome)
  • Shock or hypotension not attributable to medical therapy (e.g., sedation, renal replacement therapy)
  • Abdominal pain, vomiting, or diarrhea
  • Thrombocytopenia (platelet count <150,000/ microliter
 Evidence of SARS-CoV-2 infection AND
  • Positive SARS-CoV-2 nucleic acid amplification (NAAT), serology, or antigen test

Evidence of systemic inflammation

  • Elevated levels of at least 2 of the following: C-reactive protein (CRP), ferritin, interleukin-6 (IL-6), erythrocyte sedimentation rate (ESR), procalcitonin

*Or hospitalized for any length of time with an illness resulting in death

**Cardiac arrest alone does not meet this criterion

Reporting

  • ÐÇ¿ÕÓéÀÖ¹ÙÍø recommends all state, local, territorial, and tribal health departments use the updated CSTE/ÐÇ¿ÕÓéÀÖ¹ÙÍø MIS-C surveillance definition and case report form to conduct surveillance and report all confirmed, probable, or suspected MIS-C cases to ÐÇ¿ÕÓéÀÖ¹ÙÍø.
  • MIS-C illnesses with onset on or after January 1, 2023, to ÐÇ¿ÕÓéÀÖ¹ÙÍø should be reported using the updated case report form. See the case report form guidance document for case report form instructions.
  • MIS-C cases reported after January 1, 2023, but with illness onset before January 1, 2023, should be adjudicated using the 2020 case definition and reported using the updated case report form. See the interim case reporting guidance document for detailed instructions.
  • Cases of MIS-A can be reported to ÐÇ¿ÕÓéÀÖ¹ÙÍø using the MIS-A surveillance case report form.

MIS-C Data Available‎

Health Department-Reported Cases of Multisystem Inflammatory Syndrome in Children (MIS-C) in the United States are available on COVID Data Tracker.
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Content Source:
National Center for Immunization and Respiratory Diseases; Coronavirus and Other Respiratory Viruses Division (CORVD)
  • 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.