Changes in Treatment and Severity of Multisystem Inflammatory Syndrome in Children: An EHR-based cohort study from the RECOVER program

Objectives The purpose of this study was to examine how the treatment and severity of multisystem inflammatory syndrome in children (MIS-C) has changed over more than two years of the COVID-19 pandemic in the United States. Methods Electronic health record data were retrieved from the PEDSnet network as part of the NIH Researching COVID to Enhance Recovery (RECOVER) Initiative. The study included data for children ages 0 to 20 years hospitalized for MIS-C from March 1, 2020 through July 20, 2022. Descriptive statistics for MIS-C treatments and laboratory results were computed for three time periods of interest: March 1, 2020 – May 31, 2021 (pre-Delta); June 1 – December 31, 2021 (primarily Delta); January 1 – July 20, 2022 (primarily Omicron). Standardized differences measured the effect size of the difference between Omicron and pre-Omicron cohorts. Results The study included 946 children with a diagnosis of MIS-C. The largest differences in the Omicron period compared to prior years were decreases in the percentage of children with abnormal troponin (effect size = 0.40), abnormal lymphocytes (effect size = 0.33), and intensive care unit (ICU) visits (effect size = 0.34). There were small decreases in the Omicron period for the majority of treatments and abnormal laboratory measurements examined, including infliximab, anticoagulants, furosemide, aspirin, IVIG without steroids, echocardiograms, mechanical ventilation, platelets, ferritin, and sodium. Conclusions This study provides the first evidence that the severity of MIS-C declined in the first half of the year 2022 relative to prior years of the COVID-19 pandemic in the United States. Article Summary Using electronic health record data for 946 children, we found evidence that the severity of MIS-C declined during the first half of the year 2022. What’s Known on This Subject The clinical management of multisystem inflammatory syndrome in children (MIS-C) has commonly included intravenous immune globulin, steroids, and non-steroidal anti-inflammatory agents. Many children with MIS-C have required intravenous fluids, inotropes and vasopressors, and in some cases, mechanical ventilation. What This Study Adds Recent decreases in the percentage of children with MIS-C that have abnormal troponin, abnormal lymphocytes, or intensive care unit visits provide evidence that the severity of MIS-C has declined in the first half of the year 2022. ### Competing Interest Statement Asuncion Mejias has funding from Janssen and Merck for research support; Merck and Sanofi-Pasteur for Advisory Board participation; and AstraZeneca and Sanofi-Pasteur for CME lectures. Ravi Jhaveri is a consultant for AstraZeneca, Seqirus, Dynavax, Editorial Stipend from Pediatric Infectious Diseases Society, Royalties from UpToDate. Grant S. Schulert has consulting fees from SOBI and Novartis. The other authors have no conflicts of interest to disclose. ### Funding Statement This research was funded by the National Institutes of Health (NIH) Agreement OTA OT2HL161847 as part of the Researching COVID to Enhance Recovery (RECOVER) research program. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The Children's Hospital of Philadelphia's institutional review board designated this study as not human subjects research and waived the need for consent. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes Data will not be made available. * CDC : Centers for Disease Control and Prevention EHR : electronic health record ICU : intensive care unit IVIG : intravenous immune globulin MIS-C : multisystem inflammatory syndrome in children associated with COVID-19 PASC : Post-Acute Sequelae of SARS-CoV-2 infection