Comparing Apples to Apples in Post-COVID-Associated Multisystem Inflammatory Syndrome in Children (MIS-C) (preprint)

ABSTRACT

Background: The full clinical continuum of post-COVID-associated multisystem inflammatory syndrome of childhood (MIS-C)/Paediatric Inflammatory Multi-system Syndrome (PIMS) is still being defined, with different names and case definitions continuing to be used across jurisdictions. Refinement of criteria and better stratification of affected children will facilitate international collaborations towards improving health outcomes. Our objective is to describe the clinical characteristics and outcomes of children with MIS-C/PIMS stratified by case definition and clinical phenotype.Methods: Prospective study of 137 multi-ethnic hospitalized patients with presumed MIS-C, at a tertiary care pediatric centre in Toronto, Canada from March 2020 to February 2021. Clinical and laboratory features at presentation, organ system complications, therapeutic management, and outcomes were captured. Descriptive statistics were performed to assess differences between case definitions and clinical phenotype.Findings: The most striking differences between the case definitions were reflected in measures of disease severity and outcomes, with the MIS-C classifications capturing the more severe end of the hyperinflammatory spectrum compared to PIMS. Children in the MIS-C group were older and had more cardiac abnormalities and macrophage activation syndrome, which were reflected in more intensive care admission and corticosteroid therapy. Comparisons of clinical phenotypes (shock, Kawasaki Disease, and fever with hyperinflammation) and COVID exposure demonstrate similar clinical features, disease severity and outcomes.Interpretation: Case definition had the greatest impact on measures of disease severity, course, and outcome. Stratification by known disease phenotype led to homogeneous groupings of patients regardless of SARS-CoV-2 exposure status, confirming that recognition of known clinical entities can guide case recognition, classification and management, with our data supporting the notion that KD and MIS-C both fit on the same disease spectrum. The use of a common case definition is needed to ensure comparability in studies among international networks, reliability of public health surveillance data, and proper case ascertainment.Funding: None to declare. Declaration of Interest None to declare. Ethical Approval These studies were approved by the institutional Research Ethics Board, and the requirement for individual consent was waived.