Two years after hospitalization for multisystem inflammatory syndrome in children (MIS-C), most patients’ neurologic and psychological test scores were similar to those of controls, but those who had been admitted to an intensive care unit (ICU) and experienced reduced left ventricular ejection fraction (LVEF) tended to have diminished executive function (high-level thinking skills), concludes a study published yesterday in JAMA Network Open.

Boston Children’s Hospital researchers led the study of 59 pediatric patients diagnosed from August 2020 to August 2021 and 36 siblings, half-siblings, or cousins who served as controls. The team administered interviews, surveys, and neuropsychological evaluations and neurologic exams 6 to 12 months and 18 to 24 months after patients were released from US or Canadian hospitals. Participants were aged 5 to 20 years at release.

The study was a follow-up to one the same group conducted in 2021 and 2022 and included 86% of those participants.

“Multisystem inflammatory syndrome in children (MIS-C) is a rare but potentially life-threatening complication of SARS-CoV-2 infection,” the authors wrote. “Inflammation and multiorgan dysfunction are hallmarks, including acute neurologic symptoms, such as mental status change, seizures, and neuroinflammation.” 

Less anxiety, better sleep in year 2

In year 2, MIS-C patient outcomes were comparable to those of controls, except that they had more somatic symptoms such as headache and stomach pain (Behavior Assessment Scale for Children [BASC-3] average somatization score, 52.1 vs 46.5, respectively; average difference, 5.2). MIS-C patient scores were better at follow-up than initially, a trend not seen in controls. 

Eight of 13 children with MIS-C (62%) who had abnormal neurologic exams in year 1 had normal results by year 2. Among MIS-C patients, higher disease severity during hospitalization was associated with worse executive function in year 2 (National Institutes of Health List Sort Working Memory Test score, -7.3 points per ICU admission vs none; -5.8 points per LVEF category change; and verbal fluency switching score, -0.8 points).

Comparing year 2 with year 1, executive function scores improved in patients with MIS-C (NIH List Sort Working Memory Test average difference, 6.0 and Delis-Kaplan Executive Function System color-word interference switching subtest average difference, 1.1). 

The MIS-C group also had fewer internalizing symptoms (BASC-3 internalizing problems difference, -3.6), reflecting less anxiety, depression, and somatization (physical manifestations of stress) in year 2. Parent-reported psychosocial quality of life also improved (Pediatric Quality of Life Inventory [PedsQL] Generic Core Scale average difference, 4.7), and sleep disturbance lessened (Patient-Reported Outcomes Measurement Information System [PROMIS] sleep disturbance average difference, -3.1). 

Among the 13 MIS-C patients who had an abnormal neurologic exam in year 1 and were reexamined in year 2, 5 still had abnormal findings, primarily those involving motor skills.

Parent stress tied to worse child behavior

Fewer MIS-C patients than controls had returned to their pre-COVID baselines for energy (26% vs 11%, respectively; appetite, 16% vs 0%; sleep, 33% vs 6%; cognition, 29% vs 6%; mood, 28% vs 14%) by 2 years. Beck Youth Inventory anxiety and self-concept scores were comparable between MIS-C patients and controls, as were total sleep and activity scores.

Although the incidence of MIS-C has decreased, cases are expected to continue to occur in association with increases in COVID-19 activity, particularly among unvaccinated children or those with waning immunity.

Data newly obtained in year 2, including sleep and daily activity and parent and child mental health, suggested that greater daily activity was tied to fewer parent-reported somatic symptoms (BASC-3 somatization average difference, -0.8), while higher parent self-reported stress, anxiety, or depression on the DASS-21 was linked to worse scores on the child’s BASC-3 behavioral symptoms index (average difference, 10.2).

“Although the incidence of MIS-C has decreased, cases are expected to continue to occur in association with increases in COVID-19 activity, particularly among unvaccinated children or those with waning immunity,” the study authors wrote. 

“Patients with MIS-C had improved neurologic and psychological outcomes between the testing intervals, performing similarly to controls on most measures by year 2 follow-up,” they added. “These findings suggest that these concerns may improve over time.”

In a related commentary, Kristin Guilliams, MD, of the Washington University School of Medicine, said the study underscores the importance of monitoring patients beyond 1 year after hospital release, pediatric hospital follow-up programs to understand post-hospitalization complications and outcomes, and understanding that MIS-C is a multifactorial condition.

“In their study, Rollins et al show us that recovery after hospitalization for MIS-C is a long game to play,” she wrote. “Extended follow-up time frames and attention to sleep, activity, and family well-being are key to helping ensure children return to their prehospitalization lives as much as possible.”