Multisystem Inflammatory Syndrome in Children (MIS-C)
Multisystem Inflammatory Syndrome in Children (MIS-C) - HAN
The Council of State and Territorial Epidemiologists (CSTE) and CDC have developed a new CSTE/CDC MIS-C surveillance case definition, corresponding case report form and case report form guidance document to be used starting January 1, 2023. MIS-C cases with illness onset before January 1, 2023, but reported after January 1, 2023, will be assigned using the 2020 CDC MIS-C case definition but reported using the new case report form. An interim case reporting guidance document will be provided for these cases.
Multisystem Inflammatory Syndrome in Children (MIS-C) Associated with Coronavirus Disease 2019 (COVID-19)
Multisystem inflammatory syndrome in children (MIS-C) is a rare but severe post-infectious sequela of COVID-19 in children marked by fever, elevated inflammatory markers, and severe illness involving two or more organ systems.
In Chicago and nationally, increases in MIS-C cases have been seen 3 to 4 weeks following surges in COVID-19 cases in the community, reflecting the delay between initial SARS-CoV-2 infection and subsequent inflammatory response.
As of November 30, 2022, approximately 9,000 cases of illness in persons aged <21 years meeting the 2020 CDC MIS-C case definition had been reported in the United States through national MIS-C surveillance
COVID-19 vaccination is highly effective in preventing MIS-C, and all age-eligible children should be up-to-date with their vaccination.
All health care providers should maintain a high index of suspicion for MIS-C.
Suspected cases of MIS-C should be referred immediately to a tertiary care center with a pediatric intensive care unit (PICU).
Tertiary care centers are asked to consider a collaborative approach in the management of these patients by convening a multispecialty committee (comprised of pediatric critical care, cardiology, hematology, infectious disease, and rheumatology/immunology) that provides coordinated clinical care guidance for each patient while (1) confirming patients meet the case definition, and (2) ensuring that appropriate diagnostic and treatment resources are readily available for this patient population.
Hospital infection preventionists should be notified immediately upon recognition of patients meeting case definition to initiate public health reporting.
EVALUATION AND TESTING
A C-reactive protein ≥3.0 mg/dL (30 mg/L) is required for the CSTE/CDC MIS-C surveillance case definition. Other laboratory tests may also indicate evidence of inflammation (e.g., erythrocyte sedimentation rate, fibrinogen, procalcitonin, and ferritin).
SARS-CoV-2 testing is also indicated. Although detection of anti-nu cleocapsid antibody or anti-spike protein antibody fulfill criteria for the case definition, when feasible SARS-CoV-2 anti-nucleocapsid antibody testing is recommended, particularly in children with a history of COVID-19 vaccination because 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. Serology testing should be obtained prior to administering intravenous immunoglobulin (IVIG) or any other exogenous antibody treatments whenever possible.
In suspected cases of MIS-C, strongly recommend the following additional laboratory testing due to the potential for myocardial involvement: BNP and Troponin. Additionally, echocardiogram and electrocardiogram are usually performed given the frequent association of MIS-C with cardiac involvement.
Other imaging should be directed by patient signs or symptoms but could include: imaging to evaluate for acute appendicitis and imaging to evaluate for pharyngeal space infection.
It is important to evaluate children with suspected MIS-C for alternative diagnoses particularly as MIS-C clinical manifestations overlap with those of other etiologies. Testing to evaluate for other potential diagnoses should be directed by patient signs or symptoms. Alternate diagnoses to consider include:
Monthly Chicago MIS-C cases and COVID-19 cases, March 2020 through February 2023
Note: COVID-19 cases were counted based on specimen collection date. MIS-C cases were counted based on MIS-C illness onset date, fever onset date if illness onset date was unknown, or hospital admission date if both fever and illness onset dates were unknown.
Characteristics of Reported MIS-C Patients
MIS-C Patients by Age Group
MIS-C Patients by Sex
MIS-C Patients by Race & Ethnicity
Native Hawaiian, Other Pacific Islander
Indicators of Illness Severity
Received vasoactive medications
Eligible for vaccine at time of illness
Not eligible for vaccine at time of illness
Fully vaccinated, not boosted
*Status reflects vaccination history at time of illness onset.
Partially vaccinated means a person has received only one dose of a two-dose COVID-19 vaccine primary series.
Fully vaccinated, not boosted means a person has received all recommended doses in their primary series of COVID-19 vaccine but has not received a booster dose of vaccine.
Boosted means a person is fully vaccinated and has received a booster dose of COVID-19 vaccine.
Case Report Form: Fill the case report form as completely as possible, scan and upload the form to CDPH using the following REDCap Project: https://redcap.link/misc_afm. REDCap is a secure platform to share documents with CDPH. For instructions on filling out the case report form, please review this guidance document. MIS-C cases with illness onset before January 1, 2023, but reported after January 1, 2023, will be assigned using the 2020 CDC MIS-C case definition but reported using the new case report form. An interim case reporting guidance document can be helpful for these cases. If you need support filling out the form, please email firstname.lastname@example.org and indicate a point of contact and direct phone number for our investigators to reach you to obtain appropriate medical records to submit the form to CDC. Ideally, the case report form includes information on patient discharge but notification of the suspect case should occur right away.
I-NEDSS entry: Enter suspect MIS-C cases into the COVID-19 I-NEDSS module “Multisystem Inflammatory Syndrome”. There does not have to be a positive COVID test in order to enter into the module. It can be an epi link, COVID-like illness, or a positive molecular, antigen, or antibody test. If your lab or a commercial send out lab does not have the ability to run serologic testing, consider drawing serum and saving it prior to any treatments.
CDC Case Definition for Multisystem Inflammatory Syndrome in Children (MIS-C)
Any illness in a person aged less than 21 years that meets:
The clinical AND the laboratory criteria (Confirmed), OR
The clinical criteria AND epidemiologic linkage criteria (Probable), OR
The vital records criteria (Suspect)
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:
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:
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)
Gastrointestinal involvement indicated by:
Abdominal pain, OR
Hematologic involvement indicated by:
Platelet count <150,000 cells/μL, OR
Absolute lymphocyte count (ALC) <1,000 cells/μL
Laboratory Criteria for SARS-CoV-2 Infection
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
Epidemiologic Linkage Criteria
Close contact‡ 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
*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.