The CDC issued a Health Advisory on May 14, 2020, that outlines the following case definition for MIS-C:
Signs and symptoms include persistent fever, inflammation (on the basis of blood test results), and evidence of organ dysfunction or shock.
Although different presentations have been described, some common symptoms may include:
Common laboratory findings in case reports have included:
MIS-C is a rare complication temporally associated with COVID-19. Any child with suspected MIS-C should also be evaluated for infectious and noninfectious etiologies.
Persistent fever without a clear clinical source is the first clue. Any fever that is accompanied by symptoms concerning in their severity or coincident with recent exposure to a person with COVID-19 should raise suspicions.
Some children clinically progress rapidly and may develop hemodynamic compromise. These children should be followed and cared for in a hospital with tertiary pediatric/cardiac intensive care units.
Evaluate a child with persistent fever (≥3 days) who is moderately to severely ill with clinical signs of organ dysfunction (e.g. gastrointestinal, respiratory, skin, or neurologic). Initial evaluation should include measurement of vital signs, assessment of perfusion and oxygen saturation. Early consultation and coordination with the nearest infectious disease or rheumatology specialist and pediatric referral center for optimal testing and management should be considered. Laboratory screening for systemic inflammation may be considered and initial lab screenings may include a complete blood cell count (CBC) with differential, urine analysis, ESR, CRP, ferritin, LDH, comprehensive metabolic panel, pro-BNP, troponin, and fibrinogen.
Severely ill-appearing patients and those in compensated shock or shock should be evaluated and treated in the emergency department/critical care setting. Laboratory tests, as described above, should be performed for initial evaluation regardless of duration of fever. Consultation with pediatric subspecialists at a local or regional pediatric referral center should be initiated.
Any child sick enough to warrant admission for fever, abdominal pain, diarrhea, and/or organ dysfunction in whom MIS-C is suspected should be cared for in a hospital with tertiary pediatric/cardiac intensive care units. Although decisions about additional testing will be made by the multidisciplinary team managing the patient, pediatricians can prepare families for an expanded laboratory and cardiac workup that may include:
Clinicians who suspect MIS-C in a child should use a multidisciplinary approach involving many pediatric specialists, including but not limited to cardiology, infectious disease, immunology, hematology, rheumatology, pediatric hospital medicine, and critical care, to guide individual patient treatment.
Patients who are hospitalized with suspected MIS-C should be considered patients under investigation for COVID-19. RT-PCR and antibody testing for COVID-19 (if available) should be performed. Local infection control policies should be followed.
Patients in whom MIS-C is diagnosed should be reported to the local public health department.
Patients in whom MIS-C has been diagnosed should have close outpatient pediatric cardiology follow-up starting 2 to 3 weeks after discharge.
1Fever >38.0°C for ≥24 hours, or report of subjective fever lasting ≥24 hours.
2Including, 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.
Centers for Disease Control and Prevention. Multisystem Inflammatory Syndrome (MIS-C).
Children’s Hospital of Philadelphia. Emergency Department, ICU and Inpatient Clinical Pathway for Evaluation of Possible Multisystem Inflammatory Syndrome in Children (MIS-C).
Dufort EM, Koumans EH, Chow EJ, et al. Multisystem inflammatory syndrome in children in New York state. Published online ahead of print, June 29, 2020 Jun 29. N Engl J Med. 2020;10.1056/NEJMoa2021756. doi:10.1056/NEJMoa2021756.
Feldstein LR, Rose EB, Horwitz SM, et al. Multisystem inflammatory syndrome in U.S. children and adolescents. Published online ahead of print June 29, 2020. N Engl J Med. 2020;10.1056/NEJMoa2021680. doi:10.1056/NEJMoa2021680.
Whitaker E, Bamford A, Kenny J, et al. Clinical characteristics of 58 children with a pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2. JAMA. Published online June 8, 2020. doi:10.1001/jama.2020.10369.