Case Definitions and Reporting

Key points

The Council of State and Territorial Epidemiologists (CSTE) and CDC 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/CDC 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, "Standardized Case Definition for Surveillance of Multisystem Inflammatory Syndrome in Children" the CSTE/CDC 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

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.
Get MIS-C Data
Print
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.