Children with post-COVID syndrome show promising recovery in multicenter analysis

Six-month outcomes of children and adolescents diagnosed with multisystem inflammatory syndrome in children (MIS-C) after COVID-19 infection show normalization of cardiac function and return to nearly full baseline health for most patients, regardless of initial severity. The findings by a 39-institution collaboration working on the Multisystem Inflammatory Syndrome in Children (MUSIC) research team demonstrate a reassuring midterm prognosis result for most children and adolescents diagnosed with MIS-C.

MIS-C emerged as a serious, post-infectious complication of COVID-19 in children, presenting with fever, organ inflammation, and occasionally life-threatening cardiovascular complications. Early research indicated that many acute symptoms resolved with treatment. However, concerns about longer-term cardiac and systemic effects persisted due to limited data from large, multicenter cohorts.

The MUSIC study, “Six-Month Outcomes in the Long-Term Outcomes After the Multisystem Inflammatory Syndrome in Children Study,” published in JAMA Pediatrics, included 1,204 participants across 32 North American pediatric hospitals between March 2020 and January 2022 who met the CDC’s 2020 case definition for MIS-C.

Among the 1,204 participants, the median age was 9.1 years, 60.1% were male, 27% Black, and 26.9% Hispanic. Nearly half of the participants required vasoactive support during hospitalization, with 1.4% requiring extracorporeal membrane oxygenation. Three deaths were reported.

Researchers used echocardiography and patient-reported outcomes to assess cardiovascular and noncardiac health for six months after hospitalization. They analyzed outcomes using echocardiography core laboratory (ECL) data, descriptive statistics, regression models, and Kaplan-Meier analysis.

Primary outcomes were left ventricular ejection fraction (LVEF) and coronary artery dimensions (z scores). Secondary outcomes included overall health, return to pre-illness function, and patient-reported outcomes using the PROMIS Global Health tool. Data were collected at four intervals: hospitalization, two weeks, six weeks, and six months. Echocardiograms were reviewed by the ECL for a subset of patients due to budget constraints.

Of the participants reviewed by the ECL, 42.3% had reduced LVEF (<55%) during hospitalization. By six months, all but one had normalized cardiac function. Coronary artery aneurysms were observed in 4.4% of the cohort, with 92.3% resolving within six months. Only one participant had a persistent large/giant coronary aneurysm.

By six months, over 95% of participants reported being more than 90% recovered in domains such as energy, sleep, appetite, cognition, and mood.

Fatigue, initially reported in 15.9% of participants at two weeks, declined to 3.4% at six months. Fatigue, global health, and pain interference scores improved significantly from two weeks to six months, aligning with or surpassing pre-pandemic population norms. Neurologic and behavioral symptoms were rare, with less than 1% reporting significant issues.

Findings from the MUSIC study demonstrate a reassuring midterm prognosis for most children and adolescents diagnosed with MIS-C. Despite severe initial illness, nearly all patients recovered cardiac function and returned to baseline health by six months. Continued follow-up is ongoing to assess longer-term outcomes and guide management of this rare complication of COVID-19.

An accompanying editorial article, “Is It Safe to Exhale?”, reminds readers that the medium-term and later-term outcomes of MIS-C were unknown at the time of the study. They point to the great success of mobilizing good collaboration through a pediatric cardiac research consortium to rapidly answer important and emerging questions about MIS-C.

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