Neurological and Psychological Sequelae Associated With Multisystem Inflammatory Syndrome in Children
Authors: Rollins Caitlin K. , Calderon Johanna , Wypij David , Taylor Alex M. , Davalji Kanjiker Tahera Sultana , Rohde Julia S. , Maiman Moshe , Zambrano Laura D. , Newhams Margaret M. , Rodriguez Susan , Hart Nicholas , Worhach Jennifer , Kucukak Suden , Poussaint Tina Y. , Son Mary Beth F. , Friedman Matthew L. , Gertz Shira J. , Hobbs Charlotte V. , Kong Michele , Maddux Aline B. , McGuire Jennifer L. , Licht Paul A. , Staat Mary Allen , Yonker Lael M. , Mazumdar Maitreyi , Randolph Adrienne G. , Campbell Angela P. , Newburger Jane W. ,   Overcoming COVID-19 Investigators, Kelly Heather , Murdock Meghan , Martin Lora , Malloch Lacy , Stanley-Copeland Ashley , Craft Jeanie 
Published: July 2023

Importance

Acute 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.

Objective

To characterize neurological, psychological, and quality of life sequelae after MIS-C.

Design, Setting, and Participants

This 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.

Exposure

Diagnosis of MIS-C.

Main Outcomes and Measures

A 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.

Results

Sixty-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 Relevance

In 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.