Algorithm for the diagnosis and management of the multisystem inflammatory syndrome in children associated with COVID-19

Abstract

Objective: Although the initial reports of COVID-19 cases in children described that children were largely protected from severe manifestations, clusters of paediatric cases of severe systemic hyperinflammation and shock related to severe acute respiratory syndrome coronavirus 2 infection began to be reported in the latter half of April 2020. A novel syndrome called "multisystem inflammatory syndrome in children" (MIS-C) shares common clinical features with other well-defined syndromes, including Kawasaki disease, toxic shock syndrome and secondary hemophagocytic lymphohistiocytosis/macrophage activation syndrome. Our objective was to develop a protocol for the evaluation, treatment and follow-up of patients with MIS-C.

Methods: The protocol was developed by a multidisciplinary team. We convened a multidisciplinary working group with representation from the departments of paediatric critical care, cardiology, rheumatology, surgery, gastroenterology, haematology, immunology, infectious disease and neurology. Our protocol and recommendations were based on the literature and our experiences with multisystem inflammatory syndrome in children. After an agreement was reached and the protocol was implemented, revisions were made on the basis of expert feedback.

Conclusion: Children may experience acute cardiac decompensation or other organ system failure due to this severe inflammatory condition. Therefore, patients with severe symptoms of MIS-C should be managed in a paediatric intensive care setting, as rapid clinical deterioration may occur. Therapeutic approaches for MIS-C should be tailored depending on the patients' phenotypes. Plasmapheresis may be useful as a standard treatment to control hypercytokinemia in cases of MIS-C with severe symptoms. Long-term follow-up of patients with cardiac involvement is required to identify any sequelae of MIS-C.

FIGURE 1

Approach for evaluating patients with suspected COVID‐19 associated multisystem inflammatory syndrome in children. ALT, alanine transaminase; AST, aspartate transaminase; BUN, blood urea nitrogen; CRP, c‐reactive protein; CT: computed tomography; pro‐BNP, pro‐B‐type natriuretic peptide; ECG, electrocardiogram; ESR, erythrocyte sedimentation rate; IL‐6, interleukin‐6; KD, Kawasaki disease; MIS‐C, multisystem inflammatory syndrome in children; PT, prothrombin time; PTT, a partial thromboplastin time; RT‐PCR, real time polymerase chain reaction; SARS‐CoV‐2, Severe acute respiratory syndrome coronavirus 2. *The severity of the MIS‐C was determined by Vasoactive‐Inotropic Score (VIS), degree of respiratory support and evidence of organ injury

FIGURE 2

Treatment approach in the intensive care unit of patients with multisystem inflammatory syndrome associated with COVID‐19 in children. ACE, angiotensin converting enzyme; ARDS, acute respiratory distress syndrome; CRP, c‐reactive protein; d, days; ECMO, extracorporeal membrane oxygenation; EF, ejection fraction; g, gram; IV, intravenous; IVIG, intravenous immunoglobulin; KD, Kawasaki disease; kg, kilograms; LMWH: low‐molecular‐weight heparin; LV, left ventricular; MIS‐C, multisystem inflammatory syndrome in children; mg, milligrams; PO, by mouth, RT‐PCR, real time polymerase chain reaction; SARS‐CoV‐2, Severe acute respiratory syndrome coronavirus 2. *The severity of the MIS‐C was determined by Vasoactive‐Inotropic Score (VIS), degree of respiratory support and evidence of organ injury