Abstract: Background: Multisystem inflammatory syndrome in children (MIS-C) is associated with SARS-CoV-2 infection. Most previous studies on MIS-C are case reports or reviews, with refractory MIS-C only documented in individual case reports. Objective: To explore the differences between refractory MIS-C and non-refractory MIS-C and to enhance understanding of the disease. Design: Case-control study. Methods: Consecutive cases of MIS-C from six hospitals in Zhejiang Province were collected. Refractory MIS-C was defined as persistent fever and/or terminal organ involvement after first-line treatment (case group), while the remaining cases were classified as non-refractory MIS-C (control group). The basic information, clinical manifestations, laboratory tests, imaging findings, treatment, and efficacy of the two groups were summarized and analyzed using univariate analysis. Main outcome measures: Clinical characteristics of MIS-C. Results: A total of 23 children with MIS-C were included in this analysis, with an average onset age of 4.8±3.4 years. The interval between SARS-CoV-2 infection or exposure and MIS-C diagnosis was 30±9 days. The case group included 4 children (2 males and 2 females), while the control group included 19 children (10 males and 9 females). There were no statistically significant differences between the two groups in terms of basic information, clinical manifestations, or severe complications. In imaging findings, the case group had higher proportions of involvement in ≥2 serous cavities (75% vs . 16%) and pericardial effusion (75% vs . 11%) compared to the control group. In laboratory tests, the case group showed lower platelet (PLT) counts, higher procalcitonin (PCT), and D-dimer levels, as well as elevated levels of IL-6, IL-10, and IFN-γ, all of which were statistically significant. In the control group, 8 cases (42%) were treated with IVIG alone, 4 cases (21%) with corticosteroids alone, and 6 cases (32%) with a combination of IVIG and corticosteroids. In the case group, all 4 children received additional tocilizumab treatment on top of corticosteroids and IVIG. All 23 children improved and were discharged, with no fatalities. One child in the control group experienced severe intracranial hemorrhage and was left with hemiplegia at discharge and during a 6-month follow-up, but was lost to follow-up thereafter. Another child with coronary artery dilation returned to normal after 1 month of post-discharge follow-up. Conclusion: MIS-C can lead to severe complications such as intracranial hemorrhage, macrophage activation syndrome (MAS), and coronary artery dilation, but generally has a relatively good prognosis. Children with refractory MIS-C exhibit more intense inflammatory responses and more significant multisystem involvement. Tocilizumab is effective in treatment.

Key words: SARS-CoV-2, Multisystem inflammatory syndrome in children, Coronary artery dilation, Intracranial hemorrhage, Macrophage activation syndrom, Tocilizumab