Monocyte anisocytosis increases during multisystem inflammatory syndrome in children with cardiovascular complications

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) is a life-threatening complication that can develop weeks to months after an initial SARS-CoV-2 infection. A complex, time-consuming laboratory evaluation is currently required to distinguish MIS-C from other illnesses. New assays are urgently needed early in the evaluation process to expedite MIS-C workup and initiate treatment when appropriate. This study aimed to measure the performance of a monocyte anisocytosis index, obtained on routine complete blood count (CBC), to rapidly identify subjects with MIS-C at risk for cardiac complications. METHODS: We measured monocyte anisocytosis, quantified by monocyte distribution width (MDW), in blood samples collected from children who sought medical care in a single medical center from April 2020 to October 2020 (discovery cohort). After identifying an effective MDW threshold associated with MIS-C, we tested the utility of MDW as a tier 1 assay for MIS-C at multiple institutions from October 2020 to October 2021 (validation cohort). The main outcome was the early screening of MIS-C, with a focus on children with MIS-C who displayed cardiac complications. The screening accuracy of MDW was compared to tier 1 routine laboratory tests recommended for evaluating a child for MIS-C. RESULTS: We enrolled 765 children and collected 846 blood samples for analysis. In the discovery cohort, monocyte anisocytosis, quantified as an MDW threshold of 24.0, had 100% sensitivity (95% CI 78–100%) and 80% specificity (95% CI 69–88%) for identifying MIS-C. In the validation cohort, an initial MDW greater than 24.0 maintained a 100% sensitivity (95% CI 80–100%) and monocyte anisocytosis displayed a diagnostic accuracy greater that other clinically available hematologic parameters. Monocyte anisocytosis decreased with disease resolution to values equivalent to those of healthy controls. CONCLUSIONS: Monocyte anisocytosis detected by CBC early in the clinical workup improves the identification of children with MIS-C with cardiac complications, thereby creating opportunities for improving current practice guidelines.