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Treatment of multisystem inflammatory syndrome in children

Treatment of multisystem inflammatory syndrome in children
Treatment of multisystem inflammatory syndrome in children

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. (Funded by the European Union's Horizon 2020 Program and others; BATS ISRCTN number, ISRCTN69546370.).

Adolescent, Antibodies, Viral, COVID-19/drug therapy, Child, Child, Preschool, Cohort Studies, Confidence Intervals, Drug Therapy, Combination, Female, Glucocorticoids/therapeutic use, Hospitalization, Humans, Immunoglobulins, Intravenous/therapeutic use, Immunomodulation, Male, Propensity Score, Regression Analysis, Respiration, Artificial, SARS-CoV-2/immunology, Systemic Inflammatory Response Syndrome/drug therapy, Treatment Outcome
0028-4793
11-22
McArdle, Andrew J.
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Vito, Ortensia
8680c5c4-4391-4466-8d72-a9ee6cde1472
Patel, Harsita
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Seaby, Eleanor G.
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Shah, Priyen
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Wilson, Clare
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Broderick, Claire
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Nijman, Ruud
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Tremoulet, Adriana H.
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Munblit, Daniel
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Ulloa-Gutierrez, Rolando
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Carter, Michael J.
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De, Tisham
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Hoggart, Clive
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Whittaker, Elizabeth
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Herberg, Jethro A.
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Kaforou, Myrsini
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Cunnington, Aubrey J.
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Levin, Michael
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Vazquez, Jorge Agrimbau
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Carmona, Rodrigo
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Perez, Laura
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Rubinos, Mayra
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Veliz, Natalia
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Yori, Silvana
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Haerynck, Filomeen
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Hoste, Levi
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Leal, Izabel Alves
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Da Silva, Andre Ricardo Araujo
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Silva, Anna Esther Araujo
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Barchik, Andrea
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Barreiro, Sabrina T.A.
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Cochrane, Natalia
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Teixeira, Cristiane Henriques
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Arauj, Julienne Martins
3e209d17-b64b-482c-aafb-65549ddacd99
Ossa, Rolando Andres Paternina De La
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Vieira, Cristina Souza
40eb3995-e04d-4da8-b244-292b85310126
Dimitrova, Anna
9deddb27-cea8-461b-b78e-312b7355d138
Ganeva, Margarita
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Stefanov, Stefan
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Telcharova-Mihaylovska, Albena
e9061cb6-0c6d-4afd-9c8c-9334d2b011b1
Biggs, Catherine M.
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Scuccimarri, Rosie
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Withington, Davinia
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Raul, Bustos B.
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Ampuero, Camila
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Aravena, Javiera
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Casanova, Daniel
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Gong, Chen
87b47340-ac16-471b-96aa-f409de31d5ac
Johnson, Sarah
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BATS Consortium
McArdle, Andrew J.
bf8887df-592c-4d2d-804e-0532bf14f9e9
Vito, Ortensia
8680c5c4-4391-4466-8d72-a9ee6cde1472
Patel, Harsita
ac258fdc-38d4-4d05-b4c8-eb5c0631c7fe
Seaby, Eleanor G.
ec948f42-007c-4bd8-9dff-bb86278bf03f
Shah, Priyen
1b71f2ac-5ac3-46aa-b56d-09ddf40fb6f0
Wilson, Clare
807595f7-b35c-4816-90cc-dff791e1086c
Broderick, Claire
124bdafd-7427-41cb-8bfc-06264c731e55
Nijman, Ruud
a5acddd6-863b-4968-8099-2b15e802d604
Tremoulet, Adriana H.
d0ff5521-2fef-45b1-93d9-672717f562d5
Munblit, Daniel
caebf4a0-0825-43df-b797-a9d5ca7a475f
Ulloa-Gutierrez, Rolando
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Carter, Michael J.
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De, Tisham
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Hoggart, Clive
cf1c9469-2c64-4ce9-848c-558a7a873c41
Whittaker, Elizabeth
fed4bf4b-de8f-4656-9fa6-c8900d60fb88
Herberg, Jethro A.
70a01329-d08a-4ab3-8fa6-94c674dd8f20
Kaforou, Myrsini
1879e76e-bd2e-4637-bf5f-18664143f446
Cunnington, Aubrey J.
9efadd34-ccd8-4062-8513-f99ec4d6642d
Levin, Michael
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Vazquez, Jorge Agrimbau
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Carmona, Rodrigo
fdb6e6cd-5d73-4b86-85b8-31e81bb9b5dc
Perez, Laura
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Rubinos, Mayra
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Veliz, Natalia
67454b22-4881-435c-a4e4-63228d8b5b1b
Yori, Silvana
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Haerynck, Filomeen
49074e26-7cb6-458a-8be1-59daa09fe6b3
Hoste, Levi
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Leal, Izabel Alves
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Da Silva, Andre Ricardo Araujo
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Silva, Anna Esther Araujo
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Barchik, Andrea
98a69a9e-7deb-4067-b52b-098f16ed5339
Barreiro, Sabrina T.A.
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Cochrane, Natalia
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Teixeira, Cristiane Henriques
49a51585-a783-4368-8604-ea17ebd57b31
Arauj, Julienne Martins
3e209d17-b64b-482c-aafb-65549ddacd99
Ossa, Rolando Andres Paternina De La
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Vieira, Cristina Souza
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Dimitrova, Anna
9deddb27-cea8-461b-b78e-312b7355d138
Ganeva, Margarita
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Stefanov, Stefan
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Telcharova-Mihaylovska, Albena
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Biggs, Catherine M.
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Scuccimarri, Rosie
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Withington, Davinia
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Raul, Bustos B.
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Ampuero, Camila
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Aravena, Javiera
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Casanova, Daniel
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Gong, Chen
87b47340-ac16-471b-96aa-f409de31d5ac
Johnson, Sarah
2a02503a-b573-4ff6-8cf4-4905c70efc6f

McArdle, Andrew J., Vito, Ortensia, Patel, Harsita, Seaby, Eleanor G., Shah, Priyen and Wilson, Clare , BATS Consortium (2021) Treatment of multisystem inflammatory syndrome in children. New England Journal of Medicine, 385 (1), 11-22. (doi:10.1056/NEJMoa2102968).

Record type: Article

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. (Funded by the European Union's Horizon 2020 Program and others; BATS ISRCTN number, ISRCTN69546370.).

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More information

Published date: 1 July 2021
Additional Information: 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.
Keywords: Adolescent, Antibodies, Viral, COVID-19/drug therapy, Child, Child, Preschool, Cohort Studies, Confidence Intervals, Drug Therapy, Combination, Female, Glucocorticoids/therapeutic use, Hospitalization, Humans, Immunoglobulins, Intravenous/therapeutic use, Immunomodulation, Male, Propensity Score, Regression Analysis, Respiration, Artificial, SARS-CoV-2/immunology, Systemic Inflammatory Response Syndrome/drug therapy, Treatment Outcome

Identifiers

Local EPrints ID: 453339
URI: http://eprints.soton.ac.uk/id/eprint/453339
ISSN: 0028-4793
PURE UUID: e5132e83-07f2-475c-8691-4e8588844045
ORCID for Eleanor G. Seaby: ORCID iD orcid.org/0000-0002-6814-8648

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Date deposited: 13 Jan 2022 17:40
Last modified: 18 Mar 2024 04:00

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Contributors

Author: Andrew J. McArdle
Author: Ortensia Vito
Author: Harsita Patel
Author: Eleanor G. Seaby ORCID iD
Author: Priyen Shah
Author: Clare Wilson
Author: Claire Broderick
Author: Ruud Nijman
Author: Adriana H. Tremoulet
Author: Daniel Munblit
Author: Rolando Ulloa-Gutierrez
Author: Michael J. Carter
Author: Tisham De
Author: Clive Hoggart
Author: Elizabeth Whittaker
Author: Jethro A. Herberg
Author: Myrsini Kaforou
Author: Aubrey J. Cunnington
Author: Michael Levin
Author: Jorge Agrimbau Vazquez
Author: Rodrigo Carmona
Author: Laura Perez
Author: Mayra Rubinos
Author: Natalia Veliz
Author: Silvana Yori
Author: Filomeen Haerynck
Author: Levi Hoste
Author: Izabel Alves Leal
Author: Andre Ricardo Araujo Da Silva
Author: Anna Esther Araujo Silva
Author: Andrea Barchik
Author: Sabrina T.A. Barreiro
Author: Natalia Cochrane
Author: Cristiane Henriques Teixeira
Author: Julienne Martins Arauj
Author: Rolando Andres Paternina De La Ossa
Author: Cristina Souza Vieira
Author: Anna Dimitrova
Author: Margarita Ganeva
Author: Stefan Stefanov
Author: Albena Telcharova-Mihaylovska
Author: Catherine M. Biggs
Author: Rosie Scuccimarri
Author: Davinia Withington
Author: Bustos B. Raul
Author: Camila Ampuero
Author: Javiera Aravena
Author: Daniel Casanova
Author: Chen Gong
Author: Sarah Johnson
Corporate Author: BATS Consortium

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