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Treatment of Multisystem Inflammatory Syndrome in Children

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Andrew J McArdle, Ortensia Vito, Eleanor G Seaby, Priyen Shah, Clare Wilson, Claire Broderick, Ruud Nijman, Adriana Tremoulet, Daniel Munblit, Rolando Ulloa-Gutierrez, Michael Carter, Tisham De, Clive Hoggart, Elizabeth Whittaker, Jethro Herberg, Myrsini Kaforou, Aubrey Cunnington, Michael Levin

Original languageEnglish
Article numberDOI: 10.1056/NEJMoa2102968
Pages (from-to)11-22
Number of pages12
JournalThe New England journal of medicine
Volume385
Issue number1
DOIs
Published17 Jun 2021

Bibliographical note

Funding Information: Supported by the European Union’s Horizon 2020 Program under grants (848196 DIAMONDS and 668303 PERFORM, to Dr. Levin), by the Imperial Biomedical Research Centre (BRC) of the National Institute for Health Research (NIHR) for the enrollment of patients in London, by a grant (to Dr. McArdle) from the Lee Family Foundation, a grant (203928/Z/16/Z, to Dr. Wilson) from the Wellcome Trust, a grant (RDA02, to Dr. Broderick) from the Wellcome Trust and the BRC, grants (206508/Z/17/Z and MRF-160-0008-ELP-KAFO-C0801, to Dr. Kaforou) from the Wellcome Trust and the Medical Research Foundation, a grant (ACL-2018-021-007, to Dr. Nijman) from the NIHR, and a grant (GA5R01AI128765, to Dr. Levin) from the National Institutes of Health. Publisher Copyright: Copyright © 2021 Massachusetts Medical Society. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

King's Authors

Abstract

BACKGROUND Evidence is urgently needed to support treatment decisions for children with multisystem inflammatory syndrome (MIS-C) associated with severe acute respiratory syndrome coronavirus 2. METHODS We performed an international observational cohort study of clinical and outcome data regarding suspected MIS-C that had been uploaded by physicians onto a Web-based database. We used inverse-probability weighting and generalized linear models to evaluate intravenous immune globulin (IVIG) as a reference, as compared with IVIG plus glucocorticoids and glucocorticoids alone. There were two primary outcomes: the first was a composite of inotropic support or mechanical ventilation by day 2 or later or death; the second was a reduction in disease severity on an ordinal scale by day 2. Secondary outcomes included treatment escalation and the time until a reduction in organ failure and inflammation. RESULTS Data were available regarding the course of treatment for 614 children from 32 countries from June 2020 through February 2021; 490 met the World Health Organization criteria for MIS-C. Of the 614 children with suspected MIS-C, 246 received primary treatment with IVIG alone, 208 with IVIG plus glucocorticoids, and 99 with glucocorticoids alone; 22 children received other treatment combinations, including biologic agents, and 39 received no immunomodulatory therapy. Receipt of inotropic or ventilatory support or death occurred in 56 patients who received IVIG plus glucocorticoids (adjusted odds ratio for the comparison with IVIG alone, 0.77; 95% confidence interval [CI], 0.33 to 1.82) and in 17 patients who received glucocorticoids alone (adjusted odds ratio, 0.54; 95% CI, 0.22 to 1.33). The adjusted odds ratios for a reduction in disease severity were similar in the two groups, as compared with IVIG alone (0.90 for IVIG plus glucocorticoids and 0.93 for glucocorticoids alone). The time until a reduction in disease severity was similar in the three groups. CONCLUSIONS We found no evidence that recovery from MIS-C differed after primary treatment with IVIG alone, IVIG plus glucocorticoids, or glucocorticoids alone, although significant differences may emerge as more data accrue.

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