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. 2022 Jul;42(7):529-539.
doi: 10.1002/phar.2709. Epub 2022 Jun 27.

Early combination therapy with immunoglobulin and steroids is associated with shorter ICU length of stay in Multisystem Inflammatory Syndrome in Children (MIS-C) associated with COVID-19: A retrospective cohort analysis from 28 U.S. Hospitals

Aaron A Harthan  1 , Meghana Nadiger  2 , Jeremy S McGarvey  3 , Keith Hanson  2 , Varsha P Gharpure  4 , Erica C Bjornstad  5 , Kathleen Chiotos  6 , Aaron S Miller  7 , Ronald A Reikoff  8 , Ognjen Gajic  9 , Vishakha Kumar  10 , Allan J Walkey  11 , Rahul Kashyap  9 , Sandeep Tripathi  2 ; Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study (VIRUS): COVID-19 Registry Investigator Group
Affiliations

Early combination therapy with immunoglobulin and steroids is associated with shorter ICU length of stay in Multisystem Inflammatory Syndrome in Children (MIS-C) associated with COVID-19: A retrospective cohort analysis from 28 U.S. Hospitals

Aaron A Harthan et al. Pharmacotherapy. 2022 Jul.

Abstract

Objectives: Suggested therapeutic options for Multisystem Inflammatory Syndrome in Children (MIS-C) include intravenous immunoglobulins (IVIG) and steroids. Prior studies have shown the benefit of combination therapy with both agents on fever control or the resolution of organ dysfunction. The primary objective of this study was to analyze the impact of IVIG and steroids on hospital and ICU length of stay (LOS) in patients with MIS-C associated with Coronavirus Disease 2019 (COVID-19).

Study design: This was a retrospective study on 356 hospitalized patients with MIS-C from March 2020 to September 2021 (28 sites in the United States) in the Society of Critical Care Medicine (SCCM) Discovery Viral Infection and Respiratory Illness Universal Study (VIRUS) COVID-19 Registry. The effect of IVIG and steroids initiated in the first 2 days of admission, alone or in combination, on LOS was analyzed. Adjustment for confounders was made by multivariable mixed regression with a random intercept for the site.

Results: The median age of the study population was 8.8 (Interquartile range (IQR) 4.0, 13) years. 247/356 (69%) patients required intensive care unit (ICU) admission during hospitalization. Overall hospital mortality was 2% (7/356). Of the total patients, 153 (43%) received IVIG and steroids, 33 (9%) received IVIG only, 43 (12%) received steroids only, and 127 (36%) received neither within 2 days of admission. After adjustment of confounders, only combination therapy showed a significant decrease of ICU LOS by 1.6 days compared to no therapy (exponentiated coefficient 0.71 [95% confidence interval 0.51, 0.97, p = 0.03]). No significant difference was observed in hospital LOS or the secondary outcome variable of the normalization of inflammatory mediators by Day 3.

Conclusions: Combination therapy with IVIG and steroids initiated in the first 2 days of admission favorably impacts ICU but not the overall hospital LOS in children with MIS-C.

Keywords: COVID-19; IVIG; MIS-C; corticosteroids; outcomes.

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Conflict of interest statement

Kathleen Chiotos receives funding from the Agency for Healthcare Research and Quality (AHRQ). No COI. R.K. receives funding from the National Institutes of Health/National Heart, Lung and Blood Institute; Gordon and Betty Moore Foundation Janssen Research & Development, LLC; and royalties from Ambient Clinical Analytics. Inc. They had no influence on this manuscript's acquisition, analysis, interpretation, and reporting of pooled data. VKK receives funding from the Gordon and Betty Moore Foundation, CDC Foundation through the University of Washington, and Janssen Research & Development, LLC. They had no influence on this manuscript's acquisition, analysis, interpretation, and reporting of pooled data. AJW currently funded receives funding from the National Institutes of Health/National Heart, Lung and Blood Institute grants, Agency of Healthcare Research and Quality, Boston Biomedical Innovation Center, and royalties from UpToDate. They had no influence on this manuscript's acquisition, analysis, interpretation, and reporting of pooled data. No other authors reported any actual or potential COI related to the manuscript and associated investigation.

Figures

FIGURE 1
FIGURE 1
Flow diagram of children included in MIS‐C treatment analysis. Abbreviations: COVID‐19, Coronavirus Disease 2019; IVIG, intravenous immunoglobulin; LOS, length of stay; US, United States; VIRUS, viral infection and respiratory illness universal study
See this image and copyright information in PMC

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