1. What’s in a name?
    • Europe/UK: Paediatric Multisystem Inflammatory Syndrome temporally associated with SARS-CoV-2 infection (PMIS-TS or PIMS)
    • United States: Multi-system Inflammatory Syndrome in Children (MIS-C)
  2. Whatever you call it, in both Europe and US, there has been a temporal association of MIS-C cases being reported to occur approximately 4 weeks after the start of documented SARS-CoV-2 transmission in communities. Whether MIS-C is caused by the virus, a post-viral immune response, or other etiology is currently unknown.
  3. Time (and a comprehensive evaluation to understand immunopathogenesis!) will provide further evidence to inform whether MIS-C is indeed one condition or a manifestation of a disease spectrum, as yet not fully characterized. Currently, there are interim MIS-C case definitions to guide clinicians:
  4. While the clinical findings in MIS-C overlap with several other syndromes including toxic shock syndrome, Kawasaki disease (incomplete, KD shock), macrophage activation syndrome/hemophagocytic lymphohistiocytosis, and cytokine release syndrome, MIS-C appears to be a distinct syndrome. Similarities and differences were highlighted throughout the call.
  5. Children with MIS-C that require hospitalization have varied symptoms at presentation – these symptoms are distinct from those seen in acute, severe COVID-19. Patients with MIS-C have fever and GI symptoms (abdominal pain, diarrhea) consistently reported. The majority of reported patients (≥ 65%) with MIS-C progress to shock, which may be cardiogenic, distributive, hypovolemic, or some combination of the three. All patients develop ≥ 1 organ dysfunction – most frequently with myocardial impairment suggesting a cardiac injury similar to myocarditis; renal/AKI, GI/hepatitis, hematologic, CNS/neurologic, etc. Notably, few patients have respiratory symptoms and the need for mechanical ventilation is more often to support cardiac function or facilitate procedures than a primary pulmonary process.
  6. Initial labs in patients with MIS-C are notable for neutrophilia, lymphopenia, thrombocytopenia, and over-exuberant immune profile including markedly elevated CRP, PCT, d-dimer, ferritin, and IL-6. Markers of cardiac injury or dysfunction including troponin and BNP are abnormal. Concurrent infections are rare. Few patients have detection of SARS-CoV-2 PCR (nasopharyngeal and stool) at presentation, but most patients do have detectable antibodies (multiple platforms used)
  7. Echocardiographic findings early on often demonstrate impaired left ventricular function of variable severity as well as coronary artery dilations and rarely, coronary artery aneurysms. Serial echocardiography and follow up with cardiology should be ensured
  8. The optimal management of MIS-C beyond intensive care support to reverse shock is unknown and best practices are evolving. Many centers consider use of IVIG, including in in patients who satisfy 2017 AHA KD criteria; some centers also prescribe other immunomodulators (corticosteroids, anakinra, infliximab, and less frequently tocilizumab) in patients with ongoing inflammation. ID physicians are strongly encouraged (as always) to participate in multi-disciplinary discussions with local institutional experts in intensive care, rheumatology, cardiology, hematology, etc to develop best management plans for individual patients.
  9. Understanding the immunopathogenesis of MIS-C will allow us to provide targeted therapies. There are research efforts ongoing and clinicians are encouraged to contribute to the advancement of the science.
  10. Unknowns: a lot! MIS-C needs thoughtful, systematic study, and ongoing, multi-disciplinary collaboration. #WeAreID (pedsID, that is!)

Published literature review re: MIS-C and severe COVID-19 in children (as of 5/19/20):

Additional resources