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Multicenter Study
. 2025 Mar 1;179(3):293-301.
doi: 10.1001/jamapediatrics.2024.5466.

Six-Month Outcomes in the Long-Term Outcomes After the Multisystem Inflammatory Syndrome in Children Study

Dongngan T Truong  1   2 , Felicia L Trachtenberg  3 , Chenwei Hu  3 , Gail D Pearson  4 , Kevin Friedman  5 , Arash A Sabati  6 , Audrey Dionne  5 , Matthew E Oster  7 , Brett R Anderson  8   9 , Joseph Block  10 , Tamara T Bradford  11 , M Jay Campbell  12 , Laura D'Addese  13 , Kirsten B Dummer  14 , Matthew D Elias  15 , Daniel Forsha  16 , Olukayode D Garuba  17 , Keren Hasbani  18 , Kerri Hayes  3 , Camden Hebson  19 , Pei-Ni Jone  20   21 , Anita Krishnan  22 , Sean Lang  23 , Brian W McCrindle  24 , Kimberly E McHugh  25 , Elizabeth C Mitchell  26 , Tonia Morrison  15 , Juan Carlos Muniz  27 , R Mark Payne  28 , Michael A Portman  29 , Mark W Russell  30 , Yamuna Sanil  31 , Divya Shakti  32 , Kavita Sharma  33 , J Ryan Shea  34 , Michelle Sykes  35   36 , Lara S Shekerdemian  37 , Jacqueline Szmuszkovicz  38 , Deepika Thacker  39 , Jane W Newburger  5 ; MUSIC Study Investigators
Collaborators, Affiliations
Multicenter Study

Six-Month Outcomes in the Long-Term Outcomes After the Multisystem Inflammatory Syndrome in Children Study

Dongngan T Truong et al. JAMA Pediatr. .

Abstract

Importance: Multisystem inflammatory syndrome in children (MIS-C) is a life-threatening complication of COVID-19 infection. Data on midterm outcomes are limited.

Objective: To characterize the frequency and time course of cardiac dysfunction (left ventricular ejection fraction [LVEF] <55%), coronary artery aneurysms (z score ≥2.5), and noncardiac involvement through 6 months after MIS-C.

Design, setting, and participants: This cohort study enrolled participants between March 2020 and January 2022 with a follow-up period of 2 years. Participants were recruited from 32 North American pediatric hospitals, and all participants met the 2020 Centers for Disease Control and Prevention case definition of MIS-C.

Exposure: MIS-C after COVID-19 infection.

Main outcomes and measures: Outcomes included echocardiography core laboratory (ECL) assessments of LVEF and maximum coronary artery z scores (zMax); data collection on cardiac and noncardiac sequelae during hospitalization and at 2 weeks, 6 weeks, and 6 months after discharge; and age-appropriate Patient-Reported Outcomes Measurement Information Systems (PROMIS) Global Health Instruments at follow-up. Descriptive statistics, linear regression models, and Kaplan-Meier analysis were used.

Results: Of 1204 participants (median [IQR] age, 9.1 [5.6-12.7] years; 724 male [60.1%]), 325 self-identified with non-Hispanic Black race (27.0%) and 324 with Hispanic ethnicity (26.9%). A total of 548 of 1195 participants (45.9%) required vasoactive support, 17 of 1195 (1.4%) required extracorporeal membrane oxygenation, and 3 (0.3%) died during hospitalization. Of participants with echocardiograms reviewed by the ECL (n = 349 due to budget constraints), 131 of 322 (42.3%) had LVEF less than 55% during hospitalization; of those with follow-up, all but 1 normalized by 6 months. Black race (vs other/unknown race), higher C-reactive protein level, and abnormal troponin level were associated with lowest LVEF (estimate [SE], -3.09 [0.98]; R2 = 0.14; P =.002). Fifteen participants had coronary artery z scores of 2.5 or greater at any time point; 1 participant had a large/giant aneurysm. Of the 13 participants with z scores of 2.5 or greater during hospitalization, 12 (92.3%) had normalized by 6 months. Return to greater than 90% of pre-MIS-C health status (energy, sleep, appetite, cognition, and mood) was reported by 711 of 824 participants (86.3%) at 2 weeks, increasing to 548 of 576 (95.1%) at 6 months. Fatigue was the most common symptom reported at 2 weeks (141 of 889 [15.9%]), falling to 3.4% (22 of 638) by 6 months. PROMIS Global Health parent/guardian proxy median T scores for fatigue, global health, and pain interference improved significantly from 2 weeks to 6 months (fatigue, 56.1 vs 48.9; global health, 48.8 vs 51.3; pain interference, 53.0 vs 43.3; P < .001) and by the 6-week visit were at least equivalent to prepandemic population norms.

Conclusions and relevance: Results of this cohort study suggest that although children and young adults with MIS-C can have severe disease during the acute phase, most recovered quickly and had a reassuring midterm prognosis.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Truong reported receiving grants from the National Institutes of Health (NIH) and serving as co–principal investigator for Pfizer for research on COVID-19 vaccine-associated myocarditis funded by Pfizer and occurring through the framework of the National Heart, Lung, and Blood Institute (NHLBI)’s Pediatric Heart Network outside the submitted work. Dr Trachtenberg reported receiving grants from the NHLBI during the conduct of the study. Dr Dionne reported receiving grants from the NHLBI, Pfizer, and Boston Scientific outside the submitted work. Dr Oster reported receiving grants from the NIH NHLBI during the conduct of the study. Dr Anderson reported receiving grants from the NIH/NHLBI (R01 HL150044; UM1 HL172720) outside the submitted work. Dr Bradford reported receiving grants from the NHLBI during the conduct of the study. Dr Campbell reported receiving grants from the Centers for Disease Control and Prevention Clinical Immunization Safety Assessment Project as a subject matter expert during the conduct of the study. Dr Dummer reported receiving financial support as coordinator and principal study investigator from the NIH NHLBI and Pediatric Heart Network (PHN) during the conduct of the study. Dr Forsha reported receiving grants from the NIH and Additional Ventures Foundation outside the submitted work. Dr Hayes reported receiving grants from the NHLBI during the conduct of the study. Dr McCrindle reported receiving consultant fees from Amryt Pharma, Chiesi, Esperion, and Ultragenyx outside the submitted work. Dr Payne reported receiving grants from the NIH and consultant fees from Larimar Therapeutics for mitochondrial therapies outside the submitted work. Dr Sanil reported receiving grants from the PHN of the NHLBI of the NIH Grabt for Long Term Outcomes after the Multisystem Inflammatory Syndrome in Children (MUSIC) study during the conduct of the study. Dr Shakti reported being an employee of Takeda Pharmaceuticals since July 2023. Dr Szmuszkovicz reported receiving funding from the NIH NHLBI funded through the NIH/PHN study during the conduct of the study. Dr Newburger reported receiving grants from the NHLBI and Pfizer on COVID-19 vaccine-associated myocarditis outside the submitted work. No other disclosures were reported.

Comment on

  • Is It Safe to Exhale?
    Goldberg DJ, Costello A, Goldstein BH. Goldberg DJ, et al. JAMA Pediatr. 2025 Mar 1;179(3):237-238. doi: 10.1001/jamapediatrics.2024.5474. JAMA Pediatr. 2025. PMID: 39804639 No abstract available.

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Supplementary concepts