Neurological and Psychological Sequelae Associated With Multisystem Inflammatory Syndrome in Children

Abstract

ImportanceAcute neurological involvement occurs in some patients with multisystem inflammatory syndrome in children (MIS-C), but few data report neurological and psychological sequelae, and no investigations include direct assessments of cognitive function 6 to 12 months after discharge.ObjectiveTo characterize neurological, psychological, and quality of life sequelae after MIS-C.Design, Setting, and ParticipantsThis cross-sectional cohort study was conducted in the US and Canada. Participants included children with MIS-C diagnosed from November 2020 through November 2021, 6 to 12 months after hospital discharge, and their sibling or community controls, when available. Data analysis was performed from August 2022 to May 2023.ExposureDiagnosis of MIS-C.Main Outcomes and MeasuresA central study site remotely administered a onetime neurological examination and in-depth neuropsychological assessment including measures of cognition, behavior, quality of life, and daily function. Generalized estimating equations, accounting for matching, assessed for group differences.ResultsSixty-four patients with MIS-C (mean [SD] age, 11.5 [3.9] years; 20 girls [31%]) and 44 control participants (mean [SD] age, 12.6 [3.7] years; 20 girls [45%]) were enrolled. The MIS-C group exhibited abnormalities on neurological examination more frequently than controls (15 of 61 children [25%] vs 3 of 43 children [7%]; odds ratio, 4.7; 95% CI, 1.3-16.7). Although the 2 groups performed similarly on most cognitive measures, the MIS-C group scored lower on the National Institutes of Health Cognition Toolbox List Sort Working Memory Test, a measure of executive functioning (mean [SD] scores, 96.1 [14.3] vs 103.1 [10.5]). Parents reported worse psychological outcomes in cases compared with controls, particularly higher scores for depression symptoms (mean [SD] scores, 52.6 [13.1] vs 47.8 [9.4]) and somatization (mean [SD] scores, 55.5 [15.5] vs 47.0 [7.6]). Self-reported (mean [SD] scores, 79.6 [13.1] vs 85.5 [12.3]) and parent-reported (mean [SD] scores, 80.3 [15.5] vs 88.6 [13.0]) quality of life scores were also lower in cases than controls.Conclusions and RelevanceIn this cohort study, compared with contemporaneous sibling or community controls, patients with MIS-C had more abnormal neurologic examinations, worse working memory scores, more somatization and depression symptoms, and lower quality of life 6 to 12 months after hospital discharge. Although these findings need to be confirmed in larger studies, enhanced monitoring may be warranted for early identification and treatment of neurological and psychological symptoms.

Post-discharge outcomes of hospitalized children diagnosed with acute SARS-CoV-2 or MIS-C

“…Nearly 30% of parents reported their child as being not recovered at a median of 1.5 years following hospitalization. Published studies of COVID-19 Syndrome in children have reported prevalence rates of 1%-66%, with higher risk in children associated with age <5 years, adolescent age, and increased severity of illness (6,18,(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43). Our study's finding that two-thirds of children were experiencing either new or continued symptoms is similar to previously published surveys (6).…”

“…Our study's finding that two-thirds of children were experiencing either new or continued symptoms is similar to previously published surveys ( 6 ). Prior work evaluating Post-COVID-19 Syndrome used various designs (e.g., single center ( 39 ), community ( 34 ), and national ( 30 , 38 , 41 , 42 ), definitions, data sources (e.g., proxy or child report surveys or in-person assessments ( 32 , 36 , 37 , 42 ), electronic health record ( 31 ), and insurance registries ( 18 ), ages (e.g., inclusive pediatric age range ( 37 ) vs. adolescents( 40 , 42 ), specific SARS-CoV-2-related condition ( 33 , 35 – 37 ), level of care, and time points, contributing to the wide-ranging prevalence estimates.…”

“…Gross measures of child function were mostly similar by recovered status; detailed neuropsychological outcomes testing research is limited, but two small studies found impairments in children with MIS-C ( 35 , 36 ). Our study found that HRQOL impairment persists well past 4 months given our longer follow-up period especially for children not recovered.…”

“…Hospital-based treatment guidelines for pediatric COVID-19 patients include steroids, which reduced hospital mortality in critically ill adults with COVID-19, and both IVIG and steroids for MIS-C (48)(49)(50)(51). In one study of MIS-C patients, steroids were not associated with later neuropsychological outcomes (36). Also, steroids, IVIG, and remdesivir were not associated with recovered status or HRQOL in children with COVID-19 (52).…”

Long COVID’s Impact on Patients, Workers, & Society: A review

“…There is currently ample evidence that autoimmunity and immune hypofunction play an important role in many patients with long COVID. [ 50 – 53 ] This includes not only the occurrence of Multisystem Inflammatory Syndrome in Children [ 54 ] but also an increase in incidence of common infections such as respiratory syncytial virus (RSV) and streptococcal disease.…”