Symptomatic coronavirus disease 2019 (COVID-19) is far less common in children than adults; only about 2% of COVID-19 cases reported to the CDC occur in persons aged <18 years. However, the comfort that children were relatively less affected by acute COVID-19 was shattered in spring 2020, when reports of a syndrome of severe inflammation and multiorgan involvement, with features of Kawasaki disease (KD) and toxic shock syndrome, first emerged from Bergamo, Italy; London; and New York City. There is intense controversy about whether the KD-like illness associated with COVID-19, termed multisystem inflammatory syndrome in children (MIS-C) by the CDC, constitutes a form of KD triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or has a different pathophysiology. Although MIS-C and KD can be difficult to distinguish on occasion, there are notable differences (1). KD occurs predominantly in young children, with 80% of affected individuals younger than 5 years of age, whereas the majority of children with MIS-C are school aged and adolescent. MIS-C is overrepresented in Black and Hispanic children, whereas the relative risk of KD is highest in Asian children. Gastrointestinal symptoms are more common in MIS-C. Patients with MIS-C have higher D-dimer, ferritin, and troponin levels compared with patients with KD but have lower platelet and absolute lymphocyte counts. Finally, patients with MIS-C are more likely to present with shock and depressed ventricular function. Recent data suggest that the pathogenesis of SARS-CoV-2 infection involves autoreactivity and an inflammatory innate immune response (2). Future research on the immunobiology of MIS-C compared with KD and their responses to therapies are urgently needed, as are data on long-term cardiac and systemic organ outcomes in MIS-C and the biology underlying those sequelae. There is also a critical need for further clinical and translational research to construct clinical care pathways for evidence-based management.
Nonstandard Abbreviations:
- COVID-19
coronavirus disease 2019
- KD
Kawasaki disease
- MIS-C
multisystem inflammatory syndrome in children
- SARS-CoV-2
severe acute respiratory syndrome coronavirus 2
Author Contributions
All authors confirmed they have contributed to the intellectual content of this paper and have met the following 4 requirements: (a) significant contributions to the conception and design, acquisition of data, or analysis and interpretation of data; (b) drafting or revising the article for intellectual content; (c) final approval of the published article; and (d) agreement to be accountable for all aspects of the article thus ensuring that questions related to the accuracy or integrity of any part of the article are appropriately investigated and resolved.
Authors' Disclosures or Potential Conflicts of Interest
No authors declared any potential conflicts of interest.
References
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