Atypical Inflammatory Syndrome Triggered by SARS-CoV-2 in Infants With Down Syndrome

PURPOSE OF THE STUDY: The aim of this study was to identify unique clinical features and immune markers in infants with Down Syndrome (DS) affected by multisystem inflammatory syndrome (MIS-C). STUDY POPULATION: Cases were 2 unrelated infant girls with DS ages 6 months (P1) and 8 months (P2) admitted to the hospital for MIS-C illness for over 4 months (n = 2). The first control group included infants without DS with MIS-C illness (n = 2) from an outpatient setting. The second control group included 10 children with DS unaffected by MIS-C illness from an outpatient setting. METHODS: This was a case-control study that compared the clinical characteristics including immune phenotyping between infants with Down Syndrome (DS) affected by MIS-C and age-matched controls with or without DS. Clinical characteristics were collected from P1 and P2 by chart review, and literature review was done for clinical characteristics of children with MIS-C without DS. Samples of blood were collected from the 2 cases and controls. Subsequently, both mass cytometry and multiplex cytokine analysis were performed. Unpaired t-tests were used to assess the significances of differences in quantitative variables between 2 groups. RESULTS: Both patients with DS and MIS-C had significant neutrophilia and profound B-cell lymphopenia when compared with children with DS without MIS-C (P = .008). Specifically, both patients had decreased memory and plasma B cell subsets, whereas naïve B cells were increased. Control patients with acute MIS-C without DS had normal B cell counts. Activated CD4 T cells were decreased in both patients. P1's neutrophils and monocytes had markedly increased intracellular interleukein-8 and interleukin-1β, but this was not seen in P2. Both patients had markedly elevated inflammatory and immune activation markers. CONCLUSIONS: Children with Down Syndrome affected by MIS-C can have an atypical and severe presentation compared with children affected by MIS-C without DS, hallmarked by significant B cell depletion, younger age of onset, prolonged hospital stay, and refractoriness to treatment.