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Association of Early Steroid Administration With Outcomes of Children Hospitalized for COVID-19 Without Multisystem Inflammatory Syndrome in Children

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To identify the key insights or developments described in this article
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Key Points

Question  What is the association between the early use of steroids and outcomes for pediatric patients hospitalized for COVID-19 without non–multisystem inflammatory syndrome in children (MIS-C)?

Findings  In this cohort study involving 1163 children, hospital length of stay for patients who received steroids within 2 days of admission did not differ significantly from those who did not receive early steroids. The margin of error does not rule out benefits in some patients.

Meaning  Early use of steroids may not affect the disease course in children with non–MIS-C COVID-19, but a definitive determination of benefit or harm from early steroid therapy in children cannot be made from this study.

Abstract

Importance  There is limited evidence for therapeutic options for pediatric COVID-19 outside of multisystem inflammatory syndrome in children (MIS-C).

Objective  To determine whether the use of steroids within 2 days of admission for non–MIS-C COVID-19 in children is associated with hospital length of stay (LOS). The secondary objective was to determine their association with intensive care unit (ICU) LOS, inflammation, and fever defervescence.

Design, Setting, and Participants  This cohort study analyzed data retrospectively for children (<18 years) who required hospitalization for non–MIS-C COVID-19. Data from March 2020 through September 2021 were provided by 58 hospitals in 7 countries who participate in the Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study (VIRUS) COVID-19 registry.

Exposure  Administration of steroids within 2 days of admission.

Main Outcomes and Measures  Length of stay in the hospital and ICU. Adjustment for confounders was done by mixed linear regression and propensity score matching.

Results  A total of 1163 patients met inclusion criteria and had a median (IQR) age of 7 years (0.9-14.3). Almost half of all patients (601/1163, 51.7%) were male, 33.8% (392/1163) were non-Hispanic White, and 27.9% (324/1163) were Hispanic. Of the study population, 184 patients (15.8%) received steroids within 2 days of admission, and 979 (84.2%) did not receive steroids within the first 2 days. Among 1163 patients, 658 (56.5%) required respiratory support during hospitalization. Overall, patients in the steroids group were older and had greater severity of illness, and a larger proportion required respiratory and vasoactive support. On multivariable linear regression, after controlling for treatment with remdesivir within 2 days, country, race and ethnicity, obesity and comorbidity, number of abnormal inflammatory mediators, age, bacterial or viral coinfection, and disease severity according to ICU admission within first 2 days or World Health Organization ordinal scale of 4 or higher on admission, with a random intercept for the site, early steroid treatment was not significantly associated with hospital LOS (exponentiated coefficient, 0.94; 95% CI, 0.81-1.09; P = .42). Separate analyses for patients with an LOS of 2 days or longer (n = 729), those receiving respiratory support at admission (n = 286), and propensity score–matched patients also showed no significant association between steroids and LOS. Early steroid treatment was not associated with ICU LOS, fever defervescence by day 3, or normalization of inflammatory mediators.

Conclusions and Relevance  Steroid treatment within 2 days of hospital admission in a heterogeneous cohort of pediatric patients hospitalized for COVID-19 without MIS-C did not have a statistically significant association with hospital LOS.

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Article Information

Accepted for Publication: July 13, 2022.

Published Online: October 3, 2022. doi:10.1001/jamapediatrics.2022.3611

Corresponding Author: Sandeep Tripathi, MD, MS, University of Illinois College of Medicine at Peoria, OSF HealthCare, Children’s Hospital of Illinois, 530 NE Glen Oak Ave, Peoria, IL 61637 (sandeept@uic.edu).

Author Contributions: Dr Tripathi and Mr McGarvey 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: Tripathi, Harthan, Bhalala, Kashyap, Walkey.

Acquisition, analysis, or interpretation of data: Tripathi, Nadiger, McGarvey, Lombardo, Gharpure, Perkins, Chiotos, Sayed, Bjornstad, Raju, Miller, Dapul, Montgomery, Boman, Arteaga, Bansal, Deo, Tekin, Gajic, Kumar, Kashyap, Walkey.

Drafting of the manuscript: Tripathi, Nadiger, McGarvey, Lombardo, Perkins, Sayed, Bhalala, Bansal, Walkey.

Critical revision of the manuscript for important intellectual content: Tripathi, Nadiger, McGarvey, Harthan, Gharpure, Perkins, Chiotos, Sayed, Bjornstad, Bhalala, Raju, Miller, Dapul, Montgomery, Boman, Arteaga, Bansal, Deo, Tekin, Gajic, Kumar, Kashyap, Walkey.

Statistical analysis: Tripathi, Nadiger, McGarvey, Sayed, Deo, Walkey.

Obtained funding: Tripathi, Kumar, Walkey.

Administrative, technical, or material support: Tripathi, Harthan, Lombardo, Perkins, Sayed, Bjornstad, Bhalala, Raju, Boman, Arteaga, Bansal, Deo, Tekin, Kumar, Kashyap, Walkey.

Supervision: Tripathi, Harthan, Bhalala, Gajic, Kumar, Kashyap, Walkey.

Conflict of Interest Disclosures: Dr Chiotos reported funding from the Agency for Healthcare Research and Quality. Drs Boman and Kumar reported grants from the Gordon and Betty Moore Foundation and Janssen Research & Development. Dr Kashyap reported grants from Gordon and Betty Moore Foundation and Janssen Research & Development LLC; funding from the National Institutes of Health/National Heart, Lung and Blood Institute; and royalties from Ambient Clinical Analytics. Dr Walkey reported grants from the Gordon and Betty Moore Foundation and Gilead, funding from the National Institutes of Health/National Heart, Lung and Blood Institute, Agency of Healthcare Research and Quality, and Boston Biomedical Innovation Center; and royalties from UpToDate. No other disclosures were reported.

Funding/Support: This study was supported by a Clinical and Translational Science Award from the National Institutes of Health National Center for Advancing Translational Sciences (UL1 TR002377). The registry is funded in part by the Gordon and Betty Moore Foundation and Janssen Research & Development LLC.

Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Group Information: A complete list of the members of the Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study (VIRUS): COVID-19 Registry Investigator Group appears in Supplement 2.

Disclaimer: The contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health.

Meeting Presentation: This work was presented at the 11th World Congress of the World Federation of Pediatric Intensive and Critical Care Societies; July 12, 2022; virtual meeting.

Additional Contributions: We thank Mary Reidy and Colleen McNamara for their contributions to the Discovery VIRUS: COVID-19 Registry activities. Neither received compensation for their contributions.

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