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 CSTE position statement, "Standardized Case Definition for Surveillance of Multisystem Inflammatory Syndrome in Children," and available on CDC's National Notifiable Diseases Surveillance System website, the CSTE/CDC case definition for MIS-C is as follows:

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

  • Clinical AND the laboratory criteria (Confirmed), OR
  • Clinical criteria AND epidemiologic linkage criteria (Probable), OR
  • Vital records criteria (Suspect)

Clinical Criteria for MIS-C

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

  • 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:
    1. Left ventricular ejection fraction <55% OR
    2. Coronary artery dilatation, aneurysm, or ectasia, OR
    3. Troponin elevated above laboratory normal range, or indicated as elevated in a clinical note
  2. Mucocutaneous involvement indicated by:
    1. Rash, OR
    2. Inflammation of the oral mucosa (e.g., mucosal erythema or swelling, drying or fissuring of the lips, strawberry tongue), OR
    3. Conjunctivitis or conjunctival injection (redness of the eyes), OR
    4. Extremity findings (e.g., erythema [redness] or edema [swelling] of the hands or feet)
  3. ShockB
  4. Gastrointestinal involvement indicated by:
    1. Abdominal pain, OR
    2. Vomiting, OR
    3. Diarrhea
  5. Hematologic involvement indicated by:
    1. Platelet count <150,000 cells/μL, OR
    2. Absolute lymphocyte count (ALC) <1,000 cells/μL

Laboratory Criteria for SARS-CoV-2 Infection

  • Detection of SARS-CoV-2 RNA in a clinical specimenC 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 specimenC up to 60 days prior to or during hospitalization, or in a post-mortem specimen, OR
  • Detection of SARS-CoV-2 specific antibodiesD in serum, plasma, or whole blood associated with current illness resulting in or during hospitalization

Epidemiologic Linkage Criteria

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

Vital Records Criteria

  • 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

MIS-A Case Definition

This definition was developed in 2021 through expert opinion and is intended to assist in identification and reporting of MIS-A cases to CDC passive surveillance.

  • A patient aged ≥21 years hospitalized for ≥24 hours, or with an illness resulting in death, who meets the following clinical and laboratory criteria. The patient should not have a more likely alternative diagnosis for the illness (e.g., bacterial sepsis, exacerbation of a chronic medical condition).

Clinical Criteria for MIS-A

Subjective fever or documented fever (≥38.0 C) for ≥24 hours prior to hospitalization or within the first THREE days of hospitalization 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, or new-onset right or left ventricular dysfunction (LVEF<50%), 2nd/3rd degree A-V block, or ventricular tachycardia. (Note: cardiac arrest alone does not meet this criterion)
  • 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

Reporting

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Content Source:
National Center for Immunization and Respiratory Diseases; Coronavirus and Other Respiratory Viruses Division (CORVD)
  1. 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.
  2. Clinician documentation of shock meets this criterion.
  3. Positive molecular or antigen results from self-administered testing using over-the-counter test kits meet laboratory criteria.
  4. 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.
  5. 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.