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. 2022 Oct 3;176(12):1208-1216.
doi: 10.1001/jamapediatrics.2022.3611. Online ahead of print.

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

Sandeep Tripathi  1 , Meghana Nadiger  1 , Jeremy S McGarvey  2 , Aaron A Harthan  3 , Monica Lombardo  4 , Varsha P Gharpure  5 , Nicholas Perkins  6 , Kathleen Chiotos  7 , Imran A Sayed  8 , Erica C Bjornstad  9 , Utpal S Bhalala  10 , Umamaheswara Raju  11 , Aaron S Miller  12 , Heda Dapul  13 , Vicki Montgomery  14 , Karen Boman  15 , Grace M Arteaga  16 , Vikas Bansal  16 , Neha Deo  17 , Aysun Tekin  16 , Ognjen Gajic  16 , Vishakha K Kumar  15 , Rahul Kashyap  16 , Allan J Walkey  18 ; Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study (VIRUS): COVID-19 Registry Investigator Group
Collaborators, Affiliations

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

Sandeep Tripathi et al. JAMA Pediatr. .

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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Conflict of interest statement

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.

Figures

Figure 1.
Figure 1.. Directed Acyclic Graph for Association of Steroids With Outcomes for Children Hospitalized With COVID-19 Without Multisystem Inflammatory Syndrome in Children
Letters represent modified directed acyclic graph symbols. L represents the condition, A the treatment, and Y the effect. R represents a proxy confounder for C. B represents the variables listed below. A box around the letter represents blocking the backdoor path. A and Y represent reality and A* and Y* measurements in the study. The difference represents bias. Selection bias: factors that influence patients getting steroids also independently predict hospital length of stay (LOS). Information bias: hospital LOS may not be the best indicator of recovery. aInflammation was indicated by the number of inflammatory mediators with abnormal values on admission. bDisease severity was measured by a composite of World Health Organization ordinal scale score of 4 or higher at admission or intensive care unit admission within 2 days of hospital admission.
Figure 2.
Figure 2.. Patient Selection CONSORT Flow Diagram
MIS-C indicates multisystem inflammatory syndrome in children; PCR, polymerase chain reaction test result; VIRUS, Viral Infection and Respiratory Illness Universal Study.
See this image and copyright information in PMC

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