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

ABSTRACT

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.