Background/Purpose: Multisystem Inflammatory Syndrome in Children (MIS-C) is a serious complication associated with COVID-19, presenting as a hyperinflammatory disorder characterized by fever and multiorgan dysfunction. Whether the MIS-C phenotype varies accordingly to the SARS-CoV-2 variants is still unclear. We aim to compare MIS-C clinical features,treatments, and outcomes across the various waves of COVID-19 dividing the patient population into three cohorts according to the pre-Delta, Delta, and Omicron MIS-C waves. Our secondary objective is to evaluate if the clinical phenotype (shock, Kawasaki Disease (KD), fever with hyperinflammation) varies across the three cohorts.

Methods: Prospective cohort study of 252 patients with MIS-C, at a tertiary care pediatric center from March 2020 to March 2022. Clinical and laboratory features, complications,outcomes, and treatments were evaluated. The association with SARS-CoV-2 variants and MIS-C cohorts was assumed based on local epidemiology and sequencing data, representing the predominant strain across the three-time periods. The starting date of each MIS-C wave for study purposes was set at two weeks after the first case of COVID-19 from that respective variant in the community, as the actual time lag for developing MIS-C iswithin 2-6 weeks after the acute infection. Descriptive statistics were performed to assess differences between the 3 MIS-C cohorts and clinical phenotypes.

Results: Of the 252 patients (150 with pre-Delta variants, 59 with Delta, 43 with Omicron), the median age was 5.2 years, 58.7% were male, and 50.0 % had SARS-CoV-2 exposure. The 3 cohorts showed a significant difference in MIS-C phenotypes distribution (p=0.003). Fever and hyperinflammation was the predominant phenotype (20%) in the pre-Delta cohort; shock represented the majority (39%) in the Delta cohort; and the KD phenotype was prevalent (67%) in the Omicron cohort. Cardiac and gastrointestinal involvements were the most common features in all the cohorts, whereas, neurological involvement was the least prevalent. The Omicron cohort had more mucocutaneous involvement compared to the others. The main difference between the variant waves was reflected in measures of complications and outcome with the MIS-C cohort associated with the Delta variant capturing the most severe phenotype with a higher incidence of shock (39%), MAS (22%), andPICU admission (34%). The proportion of children developing coronary artery lesions was similar in all groups. Among all the 3 MIS-C cohorts, the majority of patients received either IVIG alone or together with upfront steroids. Pulsed high-dose steroids and anticoagulation therapy were more commonly used among children in the Delta MIS-C cohort, findings in keeping with the prevalence of the MIS-C shock phenotype in this group.

Conclusion: The MIS-C phenotype varies accordingly to the SARS-CoV-2 variants, and patients with the Delta variant have a more severe phenotype with a greater proportion of complications. These findings provide new insights into disease phenotype and SARS-CoV-2 variants and may have important implications for diagnosis and management.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/multisystem-inflammatory-syndrome-in-children-phenotypes-vary-between-sars-cov-2-variants/