Neurocognitive, Psychosocial, and Quality of Life Outcomes After Multisystem Inflammatory Syndrome in Children Admitted to the PICU*

Abstract

OBJECTIVES: To investigate neurocognitive, psychosocial, and quality of life (QoL) outcomes in children with Multisystem Inflammatory Syndrome in Children (MIS-C) seen 3–6 months after PICU admission. DESIGN: National prospective cohort study March 2020 to November 2021. SETTING: Seven PICUs in the Netherlands. PATIENTS: Children with MIS-C (0–17 yr) admitted to a PICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Children and/or parents were seen median (interquartile range [IQR] 4 mo [3–5 mo]) after PICU admission. Testing included assessment of neurocognitive, psychosocial, and QoL outcomes with reference to Dutch pre–COVID-19 general population norms. Effect sizes (Hedges’ g ) were used to indicate the strengths and clinical relevance of differences: 0.2 small, 0.5 medium, and 0.8 and above large. Of 69 children with MIS-C, 49 (median age 11.6 yr [IQR 9.3–15.6 yr]) attended follow-up. General intelligence and verbal memory scores were normal compared with population norms. Twenty-nine of the 49 followed-up (59%) underwent extensive testing with worse function in domains such as visual memory, g = 1.0 (95% CI, 0.6–1.4), sustained attention, g = 2.0 (95% CI 1.4–2.4), and planning, g = 0.5 (95% CI, 0.1–0.9). The children also had more emotional and behavioral problems, g = 0.4 (95% CI 0.1–0.7), and had lower QoL scores in domains such as physical functioning g = 1.3 (95% CI 0.9–1.6), school functioning g = 1.1 (95% CI 0.7–1.4), and increased fatigue g = 0.5 (95% CI 0.1–0.9) compared with population norms. Elevated risk for posttraumatic stress disorder (PTSD) was seen in 10 of 30 children (33%) with MIS-C. Last, in the 32 parents, no elevated risk for PTSD was found. CONCLUSIONS: Children with MIS-C requiring PICU admission had normal overall intelligence 4 months after PICU discharge. Nevertheless, these children reported more emotional and behavioral problems, more PTSD, and worse QoL compared with general population norms. In a subset undergoing more extensive testing, we also identified irregularities in neurocognitive functions. Whether these impairments are caused by the viral or inflammatory response, the PICU admission, or COVID-19 restrictions remains to be investigated.

Neurological and Psychological Sequelae Associated With Multisystem Inflammatory Syndrome in Children

“…Two earlier clinic-based studies directly assessed longer-term neurological outcomes in children after MIS-C. Penner et al found that 6 months after hospitalization, 39% of children had abnormal neurological examination findings, compared with 25% in our study. Our lower rate of neurological abnormalities may reflect fewer neurological sequelae associated with more recent SARS-CoV-2 variants, earlier recognition of MIS-C, relaxation of restrictions, or improvements in MIS-C treatment .…”

“…Our lower rate of neurological abnormalities may reflect fewer neurological sequelae associated with more recent SARS-CoV-2 variants, earlier recognition of MIS-C, relaxation of restrictions, or improvements in MIS-C treatment . A recent Dutch study of children hospitalized in the ICU for MIS-C found normal intelligence but increased emotional problems and lower quality of life than population norms 4 months after hospitalization. We found a similar pattern in MIS-C cases compared with community-based controls more than 6 months after discharge, despite easing pandemic restrictions that may have affected physical activity, mental health care, and education.…”

“…Few data address long-term noncardiac outcomes for MIS-C, and follow-up care varies among institutions . One study of MIS-C in the United Kingdom found that among 46 patients assessed 6 months after discharge, 39% had abnormal neurological examination, and 22% reported severe emotional difficulties on the Pediatric Quality of Life Inventory (PedsQL).…”

“…Follow-up was clinic based, without a control sample for comparison, and the study was conducted amid early pandemic restrictions, which may have influenced outcomes. Recently, a clinic-based study conducted in the Netherlands found psychological and quality of life sequelae 4 months after MIS-C. Longer-term follow-up and controls were not available for comparison.…”

Impaired Neurocognition, Quality of Life, and Behavior Following Multisystem Inflammatory Syndrome in Children: A Result of the Illness or the Pandemic?*

“…Despite these limitations, the study by Otten et al (14) highlights the importance of comprehensive patient follow-up and the unique benefits of incorporating standardized PICU follow-up into routine clinical care. The Dutch Association for Pediatrics has implemented a guideline of care that recommends that every PICU in the Netherlands provide follow-up for patients with unplanned admissions, those who are previously healthy, and those who experience organ failure or receive PICU therapies such as mechanical ventilation or central venous access.…”