Multisystem inflammatory syndrome in children (MIS-C) is a rare but serious complication associated with COVID-19. Patients with MIS-C have presented with a persistent fever, abdominal pain, vomiting, diarrhea, skin rash, mucocutaneous lesions and in severe cases, hypotension and shock. Patients have elevated inflammatory markers and, in a majority, laboratory markers of damage to the heart.
Not all children will have the same signs and symptoms, and some children may have symptoms not listed here. A child under investigation for MIS-C should also be evaluated for other infectious (e.g. septic shock) and non-infectious (e.g., malignancy) etiologies that may explain the clinical presentation.
MIS-C may begin weeks after a child is infected with SARS-CoV-2. The child may have been infected from an asymptomatic contact and, in some cases, the child and their caregivers may not even know they had been infected.
Most children diagnosed with MIS-C have had laboratory evidence of either past or current COVID-19 infection and the majority have had no documented underlying medical conditions.
Information on laboratory evaluation, treatment, follow-up, and other clinical considerations for patients with suspected or diagnosed MIS-C have been provided by the CDC, American Academy of Pediatrics and a recently published guidance from the American College of Rheumatology which also compares and contrasts features of MIS-C and Kawasaki disease as well as providing guidance evaluation and treatment.
- An individual aged <21 years presenting with feveri, laboratory evidence of inflammationii, and evidence of clinically severe illness requiring hospitalization, with multisystem (>2) organ involvement (cardiac, renal, respiratory, hematologic, gastrointestinal, dermatologic or neurological);AND
- No alternative plausible diagnoses; AND
- Positive for current or recent SARS-CoV-2 infection by RT-PCR, serology, or antigen test; or COVID-19 exposure within the 4 weeks prior to the onset of symptoms
iFever ≥38.0°C for ≥24 hours, or report of subjective fever lasting ≥24 hours
iiIncluding, but not limited to, one or more of the following: an elevated C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), fibrinogen, procalcitonin, d-dimer, ferritin, lactic acid dehydrogenase (LDH), or interleukin 6 (IL-6), elevated neutrophils, reduced lymphocytes and low albumin
- Some individuals may fulfill full or partial criteria for Kawasaki disease but should be reported if they meet the case definition for MIS-C
- Consider MIS-C in any pediatric death with evidence of SARS-CoV-2 infection
- Note that CDC and LAC DPH case definition for MIS-C differs from the case definition published by the World Health Organization (WHO).
Consider testing any patient for whom MIS-C is a clinical consideration for acute COVID-19 infection (i.e. RT-PCR) and for prior COVID-19 infection (antibody testing).
Testing aimed at identifying laboratory evidence of inflammation as listed in the Case Definition section is warranted. Similarly, SARS-CoV-2 detection by RT-PCR is indicated.
Where feasible, SARS-CoV-2 serology testing is suggested, even in the presence of positive RT-PCR or antigen testing. Any serology testing should be performed prior to administering IVIG or any other exogenous antibody treatments.
Given the frequent association of MIS-C with cardiac involvement, many centers are performing cardiac testing including, but not limited to:
- cardiac enzyme or troponin testing (per the center’s testing standards); and
- B-type natriuretic peptide (BNP) or NT-proBNP.
Other testing to evaluate multisystem involvement should be directed by patient signs or symptoms. Additionally, testing to evaluate for other potential diagnoses should be directed by patient signs or symptoms.
Providers are advised to immediately refer patients with a picture of toxic shock or Kawasaki disease to a specialist in pediatric infectious disease, rheumatology, and/or critical care, as indicated. Early diagnosis and treatment of patients meeting full or partial criteria for Kawasaki disease is critical to preventing end-organ damage and other long-term complications. Providers are advised to immediately refer patients with a picture of toxic shock or Kawasaki Disease to a specialist in pediatric infectious disease, rheumatology, and/or critical care, as indicated. Early diagnosis and treatment of patients meeting full or partial criteria for Kawasaki disease is critical to preventing end-organ damage and other long-term complications.
According to guidelines from the American Academy of Pediatrics the following ICD-10-CM diagnosis codes should be used for a child admitted to the hospital due to documented MIS-C.
U07.1, COVID-19 (principal diagnosis) and M35.81, other specified systemic involvement of connective tissue (secondary diagnosis).
Report cases that meet the CDC definition of Multisystem Inflammatory Syndrome in Children (MIS-C) by phone within 1 working day. Note patients should be reported regardless of SARS-CoV-2 PCR test result.
- Los Angeles County DPH Acute Communicable Disease Control: Call 213-240-7941
- Long Beach Health and Human Services: Call 562-570-4302.
- Pasadena Public Health Department: Call 626-744-6089.Fax to 310-605-4274
- New CDC Resources for Providers: Webpage
- New CDPH Information Sheet for Parents: Handout
- LAC DPH Health Update: Revised Isolation & Quarantine Orders, Recently Recovered Patients, MIS-C, and Resources (10-28-20) LAHAN
- LAC DPH Health Update: Multisystem Inflammatory Syndrome in Children (MIS-C) (7-18-20) LAHAN
- CDC COCA Webinar: Clinical Management of Multisystem Inflammatory Syndrome in Children (MIS-C) Associated with COVID-19: Slides Recording 07-16-20.
- COVID-19 and Multisystem Inflammatory Syndrome in Children (MIS-C) Webinar: Recorded on 6-10-20. Hosted by Children’s Hospital Los Angeles. To view the recording or download the slides, click here
- CDC Health Advisory: Multisystem Inflammatory Syndrome in Children (MIS-C) Associated with COVID-19 (5-14-20) Advisory
- LAC DPH Health Alert: Pediatric Multi-System Inflammatory Syndrome Potentially Associated with COVID-19 Note: the case definition in this LAHAN is superseded by the 5/14/20 CDC HAN above. (5-12-20) Alert
- WHO Scientific Brief: Multisystem inflammatory syndrome in children and adolescents temporally related to COVID-19. Note the WHO Case Definition differs from the CDC definition which is being used by LAC DPH. Brief
- CDC Webpage for Providers: Webpage
- CDC webpage For Parents: Multisystem Inflammatory Syndrome in Children (MIS-C) associated with COVID-19. Webpage
- Trends in Geographic and Temporal Distribution of US Children With Multisystem Inflammatory Syndrome During the COVID-19 Pandemic JAMA Pediatr Published online April 6, 2021. doi:10.1001/jamapediatrics.2021.0630
- Multisystem Inflammatory Syndrome in Children (MIS-C) Interim Guidance. American Academy of Pediatrics Guidance
- Clinical Guidance for Pediatric Patients with Multisystem Inflammatory Syndrome in Children (MIS-C) Associated with SARS-CoV-2 and Hyperinflammation in COVID-19. American College of Rheumatology Guidance
- Carlin RF et al. Discriminating MIS-C requiring treatment from common febrile conditions in outpatient settings. J Pediatr2020 Oct 13; [e-pub].https://doi.org/10.1016/j.jpeds.2020.10.013
- Paediatric multisystem inflammatory syndrome temporally associated with COVID-19. Royal College of Paediatrics and Child Health Guidance
- Hyperinflammatory shock in children during COVID-19 pandemic. Lancet (5-7-20) doi: 10.1016/S0140- 6736(20)31094
- COVID-19–Associated Multisystem Inflammatory Syndrome in Children — United States, March–July 2020. MMWR (8-14-20) doi: 10.15585/mmwr.mm6932e2
- An outbreak of severe Kawasaki-like disease at the Italian epicentre of the SARS-CoV-2 epidemic: an observational cohort study. Lancet (5-13-20) doi: 10.1016/ S0140- 6736(20)31129-6