Multisystem Inflammatory Syndrome in Children (MIS-C)
In the Spring of 2020, doctors recognized a new pattern of severe illness affecting children who had recently experienced otherwise unremarkable COVID-19 infections. The illness was named Multisystem Inflammatory Syndrome in Children (MIS-C) in the US and was characterized by fever, body-wide inflammation, and disease in several body systems severe enough to result in hospitalization. Disease incidence peaked in 2020 and declined substantially over the following years. By 2024, MIS-C incidence had reduced to fewer than 10 cases per year in California.
MIS-C patients are, by definition, under 21 and most cases occur in school age children. It remains unknown why only certain children develop the illness after COVID-19 infections and why disease incidence has declined so dramatically. COVID-19 is not unique in causing inflammatory disease after recovering from infection, the pattern has been seen with both viruses and bacteria. To better understand the potential causes, optimal treatment, and outcomes of MIS-C, CDPH conducts surveillance for MIS-C cases in conjunction with the CDC.
Reporting MIS-C cases
Clinicians should:
-
Report any hospitalized person age < 21 with a recent COVID infection and new onset of fever and systemic inflammation affecting more than 1 organ system to patient’s
local health department (LHD) (PDF). Provide or assist LHD in obtaining hospital records sufficient to complete the
MIS-C Case Reporting Form (PDF). At a minimum this will include the discharge summary and all labs/studies performed.
- Also report any person whose death certificate lists MIS-C as a cause of death or a condition contributing to death.
Contact CDPH at
covmis-c@cdph.ca.gov for assistance with reporting or request for clinical consultation.
Case Definition
To meet the case definition a patient must satisfy all Clinical Criteria AND satisfy linkage to a recent COVID-19 infection in one of three ways (see below). A patient may also meet the case definition based on vital records criteria alone (see below).
Clinical Criteria
- <21 years old
- Subjective or documented fever (temperature >38.0 C)
- Clinical severity requiring hospitalization or resulting in death.
- Evidence of systemic inflammation indicated by C-reactive protein > 3.0 mg/dL
- Absence of a more likely alternative diagnosis1
- New onset manifestations in at least two of the following categories:
- 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
- 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)
- Shock2
- Gastrointestinal involvement indicated by:
- Abdominal pain, OR
- Vomiting, OR
- Diarrhea
- Hematologic involvement indicated by:
- Platelet count <150,000 cells/μL OR
- Absolute lymphocyte count (ALC) <1,000 cells/μL
1If documented by the clinical treatment team, a final diagnosis of Kawasaki Disease should be considered an alternative diagnosis and these cases should not be reported.
2Clinician documentation of shock meets this criterion.
Linkage to recent COVID-19 infection
- Confirmatory laboratory evidence:
- Detection of SARS-CoV-2 ribonucleic acid (RNA) in a clinical specimen3 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 specimen3 up to 60 days prior to or during hospitalization, or in a post-mortem specimen, OR
- Detection of SARS-CoV-2 specific antibodies4 in serum, plasma, or whole blood associated with current illness resulting in or during hospitalization.
- Close contact5 with a confirmed or probable case of COVID-19 disease in the 60 days prior to hospitalization.
Vital Records Criteria
- A person aged <21 years whose death certificate lists MIS-C or multisystem inflammatory syndrome as an underlying cause of death or a significant condition contributing to death.
Case Classifications
Confirmed:
- Meets clinical criteria AND Confirmatory laboratory evidence linkage criteria
Probable:
- Meets clinical criteria AND Epidemiologic linkage criteria
Suspect:
- Meets the Vital records criteria
3Positive molecular or antigen results from self-administered testing using over-the-counter test kits meet laboratory criteria.
4Includes 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.
5Close 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.
Infection control precautions for possible MIS-C cases