Review of MIS-C Clinical Protocols and Diagnostic Pathways: Towards a Consensus Algorithm

BACKGROUND: The emergence of multisystem inflammatory syndrome in children (MIS-C) during the severe acute respiratory syndrome coronavirus 2 pandemic led to the development of institutional clinical pathways based on expert opinion. We assessed North American paediatric centres’ adaptation to MIS-C and analysed the degree of agreement between algorithms on tiered clinical investigations. METHODS: This study evaluated MIS-C diagnostic algorithms from 50 tertiary centres developed between May 2020 and December 2021 in the United States and Canada obtained online and through colleagues in various institutions. Descriptive statistics were used to analyse results. RESULTS: All clinical pathways used a tiered approach, and most required coronavirus disease 2019 polymerase chain reaction testing on presentation. Over one-quarter used a 24-hour fever to initiate investigations, and another quarter used 3 days. Basic biochemical workup was performed in all centres on presentation (complete blood count, inflammatory markers, hepatic, and renal functions). Specialized investigation was generally reserved for secondary testing (cardiac biomarkers, electrocardiogram and echo, and coagulation panel). Institutions were divided on several investigations for tier distribution, including urine studies, blood cultures, chest radiograph, and severe acute respiratory syndrome coronavirus 2 serology. Subspecialty consultations were reserved for second-line testing, including cardiology, infectious disease, and rheumatology. Finally, we propose a composite algorithm representative of the consulted pathways. CONCLUSIONS: Faced with an unprecedented clinical challenge, paediatric institutions responded swiftly with evaluation standardization, adapting to evolving knowledge. Most pathways agreed on initial basic screening tests followed by secondary workup including cardiac investigations. These protocols, developed during a high level of uncertainty, require comparative assessment on efficacy and superiority.