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A Step in De-MIS-tifying MIS-C: The Importance of Early Immunomodulatory Therapy in MIS-C

August 3, 2023

Editor’s Note: Dr. Claire Castellano is a resident physician in pediatrics at the Children’s Hospital of Philadelphia. In addition to her M.D., Claire has a Master’s in Public Health, focusing on global epidemiology. Claire hopes to combine her interests in medical education and global health in her career as a pediatrician. -Rachel Y. Moon, MD, Associate Editor, Digital Media, Pediatrics

COVID-19 took the world by storm and ushered in an era of newness and uncertainty. In the pediatric community, another syndrome associated with COVID-19 added to this uncertainty: the multisystem inflammatory syndrome in children, or MIS-C. Although similar to Kawasaki disease, MIS-C represented a novel hyperinflammatory syndrome that, due to being new and relatively rare, had yet to be rigorously studied. Based on data from the few studies that do exist, immunomodulation, focusing on use of intravenous immunoglobulin (IVIG) and glucocorticoids, is central to treatment. Given the dearth of evidence, Dr. Brian Jonat and Dr. Andrew Geneslaw of New York Presbyterian Morgan Stanley Children’s Hospital at Columbia University, as well as colleagues from the Department of Pediatrics at Hofstra and Weill Cornell, investigate the role of early glucocorticoid and IVIG treatment in their article, “Early Treatment of Multisystem Inflammatory Syndrome in Children,” being released early in Pediatrics this week (10.1542/peds.2023-061297).

This multi-center retrospective cohort study was carried out from March 2020 through March 2021. The authors focused on pediatric patients hospitalized for MIS-C from 3 children’s hospitals in the New York City metropolitan area. All patients received IVIG, but there was variability with regard to timing. The variable of interest was early glucocorticoid administration, defined as receiving glucocorticoids within 48 hours of arrival to the study site hospital. Patients who received late glucocorticoids or no glucocorticoids were grouped together. The primary outcome was length of hospital stay.

The adjusted analysis, accounting for differences in patient demographics (including age, gender, race, ethnicity, date of presentation) and disease severity at presentation (including symptoms, such as days of fever prior to presentation and clinical metrics such as D-dimer) revealed 2 independent findings:

  • early (within 48 hours) glucocorticoid administration is associated with 25% shorter length of hospital stay (incidence rate ratio = 0.75, p < 0.05)
  • early (within 48 hours) IVIG administration is associated with 44% shorter length of hospital stay (incidence rate ratio = 0.56, p < 0.05)

Taken together, the data suggest that early administration of either glucocorticoids or IVIG can help decrease length of hospital stay. Additionally, although they do not present the data that early glucocorticoid and early IVIG therapy combined is better than one or the other, the authors suggest that early combination therapy should be considered in treating pediatric patients with MIS-C.

But how exactly can these findings be applied to practice? Additional research is needed to investigate specifics around the optimal course of treatment, from target dosing to duration of treatment. It is also important to note the study’s limitations with regard to where and when it was carried out. The study sites were all referral hospitals, possibly introducing a selection bias towards patients who were more ill. There was also not much information about other patient outcomes, such as whether readmissions were increased for those who were discharged earlier or if there were differences in patients admitted to the pediatric intensive care unit.  Furthermore, compared to today, the study period includes only a subset of COVID-19 variants and a study population that was nearly entirely unvaccinated. Although future research is needed to parse out how variants and vaccination status may influence the severity of MIS-C presentation and its treatment, the strength of the findings still holds. This study adds important data to an otherwise limited understanding of MIS-C and its treatment.

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