Immunomodulatory Therapy for MIS-C

Abstract

CONTEXT: Studies comparing initial therapy for multisystem inflammatory syndrome in children (MIS-C) provided conflicting results. OBJECTIVE: To compare outcomes in MIS-C patients treated with intravenous immunoglobulin (IVIG), glucocorticoids, or the combination thereof. DATA SOURCES: Medline, Embase, CENTRAL and WOS, from January 2020 to February 2022. STUDY SELECTION: Randomized or observational comparative studies including MIS-C patients <21 years. DATA EXTRACTION: Two reviewers independently selected studies and obtained individual participant data. The main outcome was cardiovascular dysfunction (CD), defined as left ventricular ejection fraction < 55% or vasopressor requirement ≥ day 2 of initial therapy, analyzed with a propensity score-matched analysis. RESULTS: Of 2635 studies identified, 3 nonrandomized cohorts were included. The meta-analysis included 958 children. IVIG plus glucocorticoids group as compared with IVIG alone had improved CD (odds ratio [OR] 0.62 [0.42–0.91]). Glucocorticoids alone group as compared with IVIG alone did not have improved CD (OR 0.57 [0.31–1.05]). Glucocorticoids alone group as compared with IVIG plus glucocorticoids did not have improved CD (OR 0.67 [0.24–1.86]). Secondary analyses found better outcomes associated with IVIG plus glucocorticoids compared with glucocorticoids alone (fever ≥ day 2, need for secondary therapies) and better outcomes associated with glucocorticoids alone compared with IVIG alone (left ventricular ejection fraction < 55% ≥ day 2). LIMITATIONS: Nonrandomized nature of included studies. CONCLUSIONS: In a meta-analysis of MIS-C patients, IVIG plus glucocorticoids was associated with improved CD compared with IVIG alone. Glucocorticoids alone was not associated with improved CD compared with IVIG alone or IVIG plus glucocorticoids.

Navigating the Spectrum of Two Pediatric COVID-19 Complications: Multi-System Inflammatory Syndrome in Children and Post-Acute Sequelae of SARS-CoV-2 Infection

“…McArdle et al (2021) found a similar decreased risk of progression to the need for increased immunomodulatory therapy, but they found no significant difference in clinical progression (needing inotropic support or mechanical ventilation) or death when comparing IVIG and glucocorticoids to either therapy alone; however, they included patients that did not meet any of the strict case definitions of MIS-C [17]. A meta-analysis by Ouldali et al (2023) found improved cardiovascular outcomes associated with IVIG plus glucocorticoids when compared to either medication alone. Combination therapy was also associated with the faster resolution of fever and decreased need for secondary therapies when compared to glucocorticoids alone [18].…”

“…A meta-analysis by Ouldali et al (2023) found improved cardiovascular outcomes associated with IVIG plus glucocorticoids when compared to either medication alone. Combination therapy was also associated with the faster resolution of fever and decreased need for secondary therapies when compared to glucocorticoids alone [18]. Potential reasons for the reported differences in response to therapy in different series, besides different case definitions, include the different SARS-CoV-2 variants and the vaccination status of the children affected [19,20].…”

Metabolomic and Immunologic Discriminators of MIS-C at Emergency Room Presentation

“…Although validation studies will be challenging due to the reduced incidence of MIS-C, our data suggest that such validation is worthwhile to determine whether the use of flow cytometric assessment of TCRVβ21.3+ is a simple potential discriminator when children with clinical features of MIS-C and elevated CRP are assessed in the emergency room setting. Fast and accurate diagnostic tools are required both to avoid misdiagnosis and to ensure timely administration of immunomodulatory treatment to avoid intensive care unit admission and sequelae of delayed therapy 42 .…”

“…administration of immunomodulatory treatment to avoid intensive care unit admission and sequelae of delayed therapy 42 .…”