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Objective  The objective of this study is to evaluate pediatric patients using existing macrophage activation syndrome (MAS) and hemophagocytic lymphohistiocytosis (HLH) scoring systems to determine how these systems identify patients with cytokine storm syndrome (CSS) in the setting of a multisystem inflammatory syndrome in children (MIS‐C) and active coronavirus disease 2019 (COVID‐19) infection.    Methods  Hospitalized pediatric patients with MIS‐C and active COVID‐19 infection at a single institution were identified. Infectious data, clinical findings, and laboratory values were collected, and patients were stratified by disease severity. Eight historically used scoring systems for MAS, HLH, and CSS were examined in the cohort of patients with MIS‐C and pediatric COVID‐19.    Results  The HLH‐2004 criteria and HScore did not identify any patients as having CSS on admission, with only one patient with COVID‐19 meeting criteria at peak disease severity. The 2016 systemic juvenile idiopathic arthritis (sJIA)/MAS criteria, ferritin/erythrocyte sedimentation rate (ESR) ratio, and COVID‐19 CSS Quick Score most frequently identified CSS in this population and distinguished between COVID‐19 and MIS‐C hyperinflammation. The 2019 MAS/sJIA (MS) score and the COVID‐19–associated hyperinflammatory syndrome (cHIS) criteria were less likely to identify CSS, as the MS score overestimated CSS and the cHIS resulted in similar scores regardless of severity or disease type. The Caricchio COVID‐Cytokine Storm (COVID‐CS) criteria identified patients with COVID‐19 frequently but was less useful in MIS‐C because of its COVID‐19‐specific criteria.    Conclusion  MIS‐C and pediatric COVID‐19 result in relatively unique CSSs and patterns of inflammation. Existing scoring systems for CSSs likely do not capture the full breadth of this disease process in MIS‐C and pediatric COVID‐19.

Performance of Cytokine Storm Syndrome Scoring Systems in Pediatric COVID‐19 and Multisystem Inflammatory Syndrome in Children