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Rheumatology

Postdischarge Glucocorticoid Use and Clinical Outcomes of Multisystem Inflammatory Syndrome in Children

Educational Objective
To identify the key insights or developments described in this article
1 Credit CME
JAMA Network Open
Published Online: November 11, 2022
Original Investigation
Mary Beth F. Son, MD1,2;
Laura Berbert, MS3;
Cameron Young, BS4;
Johnathan Dallas, BS1,5;
Margaret Newhams, MPH4;
Sabrina Chen, BS4;
Stacy P. Ardoin, MD, MSc6;
Matthew L. Basiaga, DO, MSCE7;
Susan P. Canny, MD, PhD8;
Hillary Crandall, MD, PhD9;
Sanjeev Dhakal, MS10;
Anita Dhanrajani, MBBS, MSc11;
Anna Carmela P. Sagcal-Gironella, MD, MS12,13;
Charlotte V. Hobbs, MD14;
Livie Huie, BS, CCRC15;
Karen James, MD, MSCE16;
Madelyn Jones, BS6;
Susan Kim, MD, MMSc17;
Geraldina Lionetti, MD17;
Melissa L. Mannion, MD15;
Eyal Muscal, MD, MS18;
Sampath Prahalad, MD, MS19;
Grant S. Schulert, MD, PhD10;
Kristen Sexson Tejtel, MD, PhD, MPH20;
D. Sofia Villacis-Nunez, MD19;
Eveline Y. Wu, MD, MSCR21;
Laura D. Zambrano, PhD, MPH22;
Angela P. Campbell, MD, MPH22;
Manish M. Patel, MD22,23;
Adrienne G. Randolph, MD4,24;
for the Overcoming COVID-19 Investigators
Author Affiliations
  • 1Division of Immunology, Boston Children’s Hospital, Boston, Massachusetts
  • 2Department of Pediatrics, Harvard Medical School, Boston, Massachusetts
  • 3Institute Centers for Clinical and Translational Research, Boston Children’s Hospital, Harvard Medical School, Boston, Massachusetts
  • 4Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children’s Hospital, Boston, Massachusetts
  • 5Western Atlantic University School of Medicine, Freeport, Grand Bahama, Bahamas
  • 6Rheumatology, Nationwide Children’s Hospital, Department of Pediatrics, Ohio State College of Medicine, Columbus
  • 7Division of Pediatric Rheumatology, Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, Minnesota
  • 8Division of Pediatric Rheumatology, Seattle Children’s Hospital, Department of Pediatrics, University of Washington, Seattle
  • 9Division of Pediatric Critical Care, Department of Pediatrics, University of Utah, Primary Children’s Hospital, Salt Lake City
  • 10Division of Rheumatology, Cincinnati Children’s Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio
  • 11Pediatric Rheumatology, Department of Pediatrics, University of Mississippi Medical Center, Jackson
  • 12Department of Pediatrics, Hackensack Meridian School of Medicine, Hackensack, New Jersey
  • 13Division of Rheumatology, Joseph M. Sanzari Children’s Hospital, Hackensack, New Jersey
  • 14Division of Pediatric Infectious Disease, Department of Pediatrics, University of Mississippi Medical Center, Jackson
  • 15Division of Pediatric Rheumatology, University of Alabama at Birmingham
  • 16Division of Pediatric Rheumatology, Department of Pediatrics, University of Utah, Primary Children’s Hospital, Salt Lake City
  • 17Pediatric Rheumatology, UCSF Benioff Children’s Hospital, Department of Pediatrics, University of California at San Francisco School of Medicine
  • 18Division of Rheumatology, Texas Children’s Hospital, Department of Pediatrics, Baylor School of Medicine, Houston
  • 19Children’s Healthcare of Atlanta, Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia
  • 20Division of Cardiology, Texas Children’s Hospital, Department of Pediatrics, Baylor School of Medicine, Houston
  • 21Division of Pediatric Rheumatology, UNC Children’s Hospital, Department of Pediatrics, University of North Carolina School of Medicine, Chapel Hill
  • 22COVID-19 Response Team, Centers for Disease Control and Prevention, Atlanta, Georgia
  • 23Public Health Service Commissioned Corps, Rockville, Maryland
  • 24Departments of Pediatrics and Anesthesiology, Harvard Medical School, Boston, Massachusetts
  • Overcoming COVID-19 Investigatorsfor the
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Key Points

Question  What are 3-month outcomes in patients with multisystem inflammatory syndrome in children (MIS-C), and what factors are associated with use of glucocorticoids following discharge?

Findings  In this cohort study including 186 US children with MIS-C, severity of inpatient illness was not associated with duration of postdischarge glucocorticoid treatment; clinical outcomes were similar in patients prescribed shorter courses. Significant weight gain was common, but recurrent inflammation following hospital discharge was infrequent.

Meaning  The findings of this study suggest that glucocorticoid tapers of less than 3 weeks are likely sufficient to treat MIS-C following discharge; shortening tapers is an important goal to avoid morbidity.

Abstract

Importance  Minimal data are available regarding the postdischarge treatment of multisystem inflammatory syndrome in children (MIS-C).

Objectives  To evaluate clinical characteristics associated with duration of postdischarge glucocorticoid use and assess postdischarge clinical course, laboratory test result trajectories, and adverse events in a multicenter cohort with MIS-C.

Design, Setting, and Participants  This retrospective cohort study included patients with MIS-C hospitalized with severe illness and followed up for 3 months in an ambulatory setting. Patients younger than 21 years who were admitted between May 15, 2020, and May 31, 2021, at 13 US hospitals were included. Inclusion criteria were inpatient treatment comprising intravenous immunoglobulin, diagnosis of cardiovascular dysfunction (vasopressor requirement or left ventricular ejection fraction ≤55%), and availability of complete outpatient data for 3 months.

Exposures  Glucocorticoid treatment.

Main Outcomes and Measures  Main outcomes were patient characteristics associated with postdischarge glucocorticoid treatment, laboratory test result trajectories, and adverse events. Multivariable regression was used to evaluate factors associated with postdischarge weight gain (≥2 kg in 3 months) and hyperglycemia during illness.

Results  Among 186 patients, the median age was 10.4 years (IQR, 6.7-14.2 years); most were male (107 [57.5%]), Black non-Hispanic (60 [32.3%]), and Hispanic or Latino (59 [31.7%]). Most children were critically ill (intensive care unit admission, 163 [87.6%]; vasopressor receipt, 134 [72.0%]) and received inpatient glucocorticoid treatment (178 [95.7%]). Most were discharged with continued glucocorticoid treatment (173 [93.0%]); median discharge dose was 42 mg/d (IQR, 30-60 mg/d) or 1.1 mg/kg/d (IQR, 0.7-1.7 mg/kg/d). Inpatient severity of illness was not associated with duration of postdischarge glucocorticoid treatment. Outpatient treatment duration varied (median, 23 days; IQR, 15-32 days). Time to normalization of C-reactive protein and ferritin levels was similar for glucocorticoid duration of less than 3 weeks vs 3 or more weeks. Readmission occurred in 7 patients (3.8%); none was for cardiovascular dysfunction. Hyperglycemia developed in 14 patients (8.1%). Seventy-five patients (43%) gained 2 kg or more after discharge (median 4.1 kg; IQR, 3.0-6.0 kg). Inpatient high-dose intravenous and oral glucocorticoid therapy was associated with postdischarge weight gain (adjusted odds ratio, 6.91; 95% CI, 1.92-24.91).

Conclusions and Relevance  In this multicenter cohort of patients with MIS-C and cardiovascular dysfunction, postdischarge glucocorticoid treatment was often prolonged, but clinical outcomes were similar in patients prescribed shorter courses. Outpatient weight gain was common. Readmission was infrequent, with none for cardiovascular dysfunction. These findings suggest that strategies are needed to optimize postdischarge glucocorticoid courses for patients with MIS-C.

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Critical Care Medicine Pediatrics Rheumatology Coronavirus (COVID-19)
Article Information

Accepted for Publication: September 28, 2022.

Published: November 11, 2022. doi:10.1001/jamanetworkopen.2022.41622

Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2022 Son MBF et al. JAMA Network Open.

Corresponding Author: Mary Beth F. Son, MD, Division of Immunology, Boston Children’s Hospital, 300 Longwood Ave, Boston, MA 02115 (marybeth.son@childrens.harvard.edu).

Author Contributions: Dr Son and Ms Berbert had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Son, Canny, Muscal, Prahalad, Zambrano, Randolph.

Acquisition, analysis, or interpretation of data: Berbert, Young, Dallas, Newhams, Chen, Ardoin, Basiaga, Canny, Crandall, Dhakal, Dhanrajani, Sagcal-Gironella, Hobbs, Huie, James, Jones, Kim, Lionetti, Mannion, Muscal, Prahalad, Schulert, Sexson Tejtel, Villacis-Nunez, Wu, Campbell, Patel, Randolph.

Drafting of the manuscript: Son, Berbert, Young, Jones, Prahalad, Schulert.

Critical revision of the manuscript for important intellectual content: Son, Berbert, Young, Dallas, Newhams, Chen, Ardoin, Basiaga, Canny, Crandall, Dhakal, Dhanrajani, Sagcal-Gironella, Hobbs, Huie, James, Kim, Lionetti, Mannion, Muscal, Prahalad, Schulert, Sexson Tejtel, Villacis-Nunez, Wu, Zambrano, Campbell, Patel, Randolph.

Statistical analysis: Berbert, Young, Chen, Ardoin.

Obtained funding: Zambrano, Patel, Randolph.

Administrative, technical, or material support: Son, Dallas, Newhams, Ardoin, Basiaga, Dhakal, Hobbs, Huie, Jones, Kim, Mannion, Schulert, Villacis-Nunez, Zambrano, Campbell, Randolph.

Supervision: Canny, Hobbs, Mannion, Zambrano, Campbell, Patel, Randolph.

Conflict of Interest Disclosures: Dr Son reported receiving grants from the Centers for Disease Control and Prevention (CDC), salary support from the Childhood Arthritis & Rheumatology Research Alliance (CARRA), and royalties from UpToDate during the conduct of the study. Dr Basiaga reported receiving grants from CARRA and the Sjögren’s Foundation outside the submitted work. Dr Canny reported receiving grants from Overcoming COVID-19 during the conduct of the study and receiving grants from the National Institutes of Health (NIH), CARRA/Arthritis Foundation, and the Arthritis National Research Foundation outside the submitted work. Dr Hobbs reported receiving personal fees from DYNAMED.com as a clinical database reviewer, and speaker fees from Biofire/Biomerieux (2021-2022) outside the submitted work. Dr Mannion reported receiving grants from the Rheumatology Research Foundation during the conduct of the study. Dr Muscal reported being a paid member of the Swedish Orphan Biovitrum advisory board outside the submitted work. Dr Prahalad reported receiving personal fees for serving on a committee from Novartis Pharmaceuticals outside the submitted work. Dr Schulert reported receiving personal fees from Swedish Orphan Biovitrum and Novartis outside the submitted work. Dr Sexson Tejtel reported receiving grants from the NIH outside the submitted work. Dr Randolph reported receiving grants from the NIH to Boston Children's Hospital, royalties from UpToDate, and nonfinancial support from Illumina Inc for reagents outside the submitted work. No other disclosures were reported.

Funding/Support: This study was funded by the CDC under contract 75D30120C07725 to Boston Children’s Hospital.

Role of the Funder/Sponsor: The CDC technical staff were coinvestigators involved in the design and conduct of the study; interpretation of the data; preparation, review, and approval of the manuscript; and decision to submit the manuscript for publication.

Group Information: The Overcoming COVID-19 Investigators are listed in Supplement 2.

Disclaimer: The findings and conclusions in this article are those of the authors and do not necessarily represent the official position of the CDC.

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