1. In this single-center study of children hospitalized with MIS-C, most had complete recovery of cardiac function.
2. While most markers of inflammation normalized rapidly, the proportion of double-negative T-cells (DNTs) remained elevated in nearly all patients at the 4 to 9 month follow up.
Evidence Rating Level: 2 (Good)
Study Rundown: Multisystem Inflammatory Syndrome in Children (MIS-C) is one of the most severe consequences of COVID-19 exposure in pediatric patients, and commonly causes myocardial dysfunction. To date, little is known about the long-term clinical impact of this disease. In this study performed at one center in New York, researchers sought to characterize the lasting immunologic and cardiac sequelae occurring after MIS-C diagnosis in their patient population up to 9 months post-discharge. They found that most inflammatory markers resolved rapidly after discharge, and nearly all echocardiograms were normal at long term follow up. However, a significant percentage of patients had lymphocytosis at the 1 to 4 week follow up, and the proportion of DNTs (which are usually elevated in acute infection) remained elevated in the majority of patients at the 4 to 9 month follow up. Although recovery of cardiac function is reassuring, the persistence of DNTs raises questions regarding the long term impact of this syndrome on the immune system. The study was limited by its small sample size and significant loss to follow-up.
In-Depth [prospective cohort]: This study followed 45 children who were hospitalized for MIS-C at the Columbia University Irving Medical Center from April 17 – December 31, 2020. Data, including laboratory values, ECGs, and echocardiograms, were gathered during childrens’ hospital stays, and again at 1-4 weeks, 1-4 months, and 4-9 months after discharge. At presentation, 98% of patients had elevated inflammatory markers (CRP, D-dimer, ferritin), 91% had elevated NT pro-BNP, and 87% had elevated Troponin. 53% had at least moderate ventricular dysfunction, 36% had at least mild ventricular dilation, 27% had moderate to severe atrioventricular valve regurgitation, and 9% had coronary artery dilation. 12 patients underwent additional immune profiling on admission, of which 83% had lymphopenia, most had low cytotoxic T cells and natural killer cells, and 25% had low B cells. There were no deaths, and only 1 patient required intubation. Of note, all patients received IV steroids, and 89% received intravenous immune globulin (IVIG). By the 4 to 9 month follow-up visit for the 31 children who returned, 97-100% had normalized inflammatory and cardiac markers. Only two had mild ventricular dysfunction, two had ventricular dilation, eight had mild atrioventricular valve regurgitation, and none had coronary artery dilation. 24 patients were assessed for their lymphocyte subsets at the 1-4 week follow-up. 42% had lymphocytosis, and 96% had elevated levels of DNTs (later found to be gamma-delta T cells, which proliferate during periods of acute infection). DNTs remained increased in nearly all of these children who returned to follow-up throughout the study period.
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