Long-Term Outcomes After the Multisystem Inflammatory Syndrome in Children (MUSIC)

Multi-system Inflammatory Syndrome in Children (MIS-C) is a new condition related to COVID-19, the study investigators are still learning about its causes, effects, and long-term impact. "Long-Term Outcomes after the Multisystem Inflammatory Syndrome In Children", the Coronavirus MUSIC Study, is a research study funded by NIH and the National Heart, Lung, and Blood Institute. The study investigators hope to enroll at least 900 young people with MIS-C at children's medical centers in the U.S. and Canada. This research study will help us learn more about MIS-C and its effects on the long-term health of children.

Study Overview

• Status: Active, not recruiting
• Conditions: Multisystem Inflammatory Syndrome in Children (MIS-C)

Detailed Description

This study is an observational cohort study that will use routinely collected clinical and cardiac (EKG, echocardiogram, Cardiac MRI, exercise testing) data to assess the association between MIS-C and cardiac outcomes within the first year after hospital discharge. Research funding will be available for EKGs, echocardiograms and MRIs in protocol windows that are not ordered by primary caregivers. The principal goal is to determine the spectrum and early time course of coronary artery involvement, LV systolic function, and arrhythmias or conduction system abnormalities, and, using these data, to define associated clinical and laboratory factors. The study investigators planned to include all eligible patients, including retrospective cases beginning January 1, 2020, with follow-up (in-person or telehealth) to up within one year and annual medical history forms until up to 5 years have elapsed since illness onset. Because many patients will have been identified by retrospective review, the study team will obtain consent at different times in their illness course. For this reason, it may be hard to reach some patients and their families. Waiver of consent will be obtained after three attempts have been made to locate the patient and family without success, as well as for the rare child who dies before informed consent can be obtained. The study investigators will include a HIPAA-compliant cryptographic algorithm to create a sharable "hashed" identifier from patient information. If blood work for research purposes is added on to usual clinically indicated blood work during follow-up visits, this will be covered by other informed consent forms.

• Study Type: Observational
• Enrollment (Actual): 1200

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada
      • The Hospital for Sick Children
• United States
  • Alabama
    • Tuscaloosa, Alabama, United States, 35401
      • University of Alabama
  • Arizona
    • Phoenix, Arizona, United States, 85016
      • Phoenix Children's Hospital
  • California
    • Los Angeles, California, United States, 90027
      • Children's Hospital Los Angeles
    • Madera, California, United States, 93636
      • Valley Children's Healthcare and Hospital
    • San Diego, California, United States, 92131
      • UC San Diego, Rady Children's Hospital
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Children's Hospital of Colorado
  • Delaware
    • Wilmington, Delaware, United States, 19808
      • The Nemours Foundation
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20010
      • Children's National Hospital
  • Florida
    • Hollywood, Florida, United States, 33021
      • Joe DiMaggio Children's Hospital
    • Miami, Florida, United States, 33155
      • Nicklaus Children's Hospital
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Chldren's Healthcare of Atlanta
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Ann & Robert Lurid Children's Hospital of Chicago
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Riley Children's Hospital
  • Louisiana
    • New Orleans, Louisiana, United States, 70118
      • Children's Hospital of New Orleans
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Boston Children's Hospital
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • CS Mott Children's Hospital/University of Michigan
    • Detroit, Michigan, United States, 48201
      • Children's Hospital of Michigan
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • University of Mississippi
  • Missouri
    • Kansas City, Missouri, United States, 64108
      • Children's Mercy Hospital
  • New York
    • New York, New York, United States, 10032
      • Morgan Stanley Children's Hospital of New York
    • Queens, New York, United States, 11040
      • Cohen Children's Medical Center
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514
      • University of North Carolina
    • Durham, North Carolina, United States, 27705
      • Duke Children's Hospital and Health Center
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hospital of Philadelphia
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
  • Texas
    • Austin, Texas, United States, 78707
      • Dell Medical Center
    • Dallas, Texas, United States, 75235
      • Children's Medical Center of Dallas - UT Southwestern Medical Center
    • Houston, Texas, United States, 77030
      • Baylor /Texas Children's Hospital
  • Utah
    • Salt Lake City, Utah, United States, 84113
      • Primary Children's Hospital
  • Washington
    • Seattle, Washington, United States, 98105
      • Seattle Children's Hospital
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin/Children's Hospital of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 21 years (Child, Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

children and young adults <21 years with Multisystem Inflammatory Syndrome in Children associated with COVID-19 (MIS-C) at a participating hospital

Description

Inclusion Criteria:

1. Age <21 years.
2. Fever ≥38°C for ≥24 hours, or report of subjective fever lasting ≥24 hours.
3. Laboratory evidence of inflammation, including, but not limited to, one or more of the following: an elevated CRP, ESR, fibrinogen, procalcitonin, d-dimer, ferritin, LDH, or IL-6, elevated neutrophils, reduced lymphocytes and low albumin.
4. Evidence of clinically severe illness requiring hospitalization, with multisystem (≥2) organ involvement, based on clinical judgment from record review, discharge diagnosis, laboratory or diagnostic tests. Organ system involvement includes but is not limited to cardiac, renal, respiratory, hematologic including coagulopathy, gastrointestinal including liver, dermatologic or neurological.
5. Positive for current or recent SARS-CoV-2 infection by RT-PCR, serology, or antigen test; or COVID-19 exposure within the 4 weeks prior to the onset of symptoms

Exclusion Criteria:

• No plausible alternative diagnosis, such as bacterial sepsis, murine typhus, staphylococcal or streptococcal shock syndromes

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
worst-ever LV ejection fraction	worst left ventricular (LV) ejection fraction from core lab echo read during MUSIC study	hospital admission through 5 years post-hospitalization
worst-ever maximum z score of the proximal LAD or RCA	worst maximum z-score of the proximal left anterior descending coronary artery (LAD) or right coronary artery (RCA) from core lab echo read; z-scores to be calculated via Boston z-score calculator (primary) and Pediatric Heart Network z-score calculator (secondary); higher z-scores are worse	hospital admission through 5 years post-hospitalization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of a proximal LAD or RCA z score of ≥2.5 on any echocardiogram	proximal left anterior descending coronary artery (LAD) or right coronary artery (RCA) ≥2.5 from any core lab echo read	hospital admission through 5 years post-hospitalization
Occurrence of aneurysms by Japanese Ministry of Health criteria	Occurrence of aneurysms by Japanese Ministry of Health criteria applied to core lab echo reads	hospital admission through 5 years post-hospitalization
Individual z scores for LMCA, RCA and LAD	Individual z scores for left main coronary artery (LMCA), right coronary artery (RCA) and proximal left anterior descending coronary artery (LAD) as per core lab echo reads; higher z-scores are worse	hospital admission through 5 years post-hospitalization
LVEDV z score	left ventricular (LV) size as measured by left ventricular end-diastolic volume (LVEDV) z score	hospital admission through 5 years post-hospitalization
LVEF	left ventricular (LV) function as measured by left ventricular ejection fraction (LVEF)	hospital admission through 5 years post-hospitalization
LVSF	left ventricular (LV) function as measured by left ventricular shortening fraction (LVSF)	hospital admission through 5 years post-hospitalization
The percentage of patients who had LV ejection of <55%, and further categorization of 45-54% (i.e., mildly depressed systolic function), 35-44% (moderately depressed systolic function) and <35% (severely depressed systolic function) on any echocardiogram	The percentage of patients who had left ventricular (LV) ejection of <55%, and further categorization of 45-54% (i.e., mildly depressed systolic function), 35-44% (moderately depressed systolic function) and <35% (severely depressed systolic function) on any echocardiogram read by the core lab	hospital admission through 5 years post-hospitalization
LV strain (global longitudinal strain from apical view and global circumferential strain from parasternal short-axis view)	left ventricular (LV) strain (global longitudinal strain from apical view and global circumferential strain from parasternal short-axis view) on core lab echo read	hospital admission through 5 years post-hospitalization
Qualitative assessment of RV systolic function	Qualitative assessment of right ventricular (RV) systolic function on core lab echo read	hospital admission through 5 years post-hospitalization
Qualitative assessment of RV global longitudinal strain	Qualitative assessment, if possible, of right ventricular (RV) global longitudinal strain on core lab echo read	hospital admission through 5 years post-hospitalization
Presence and degree of mitral and aortic regurgitation	Presence and degree of mitral and aortic regurgitation on echo core lab read	hospital admission through 5 years post-hospitalization
LV diastolic function, i.e., tissue Doppler imaging and mitral valve (MV) inflow	left ventricular (LV) diastolic function, i.e., tissue Doppler imaging and mitral valve (MV) inflow on echo core lab read	hospital admission through 5 years post-hospitalization
Presence and size of pericardial effusion	Presence and size of pericardial effusion on echo core lab read	hospital admission through 5 years post-hospitalization
The occurrence of arrhythmias and conduction system disturbances by in-hospital monitoring, electrocardiograms, and exercise testing at 3 months in those with a history of ≥moderate systolic dysfunction when age and maturity permit	The occurrence of arrhythmias and conduction system disturbances by in-hospital monitoring, electrocardiograms, and exercise testing at 3 months in those with a history of ≥moderate systolic dysfunction when age and maturity permit	3 months post-discharge
MRI LVEF	LVEF on MRI core lab read	hospital admission through 5 years post-hospitalization
MRI RVEF	RVEF on MRI core lab read	hospital admission through 5 years post-hospitalization
valvar regurgitation	valvar regurgitation on MRI core lab read	hospital admission through 5 years post-hospitalization
myocardial late gadolinium enhancement (LGE)	percent with and distribution of myocardial late gadolinium enhancement (LGE) on MRI core lab read	hospital admission through 5 years post-hospitalization
abnormal T2-weighted imaging	percent abnormal T2-weighted imaging on MRI core lab read	hospital admission through 5 years post-hospitalization
elevated T2	percent with elevated T2 on MRI core lab read	hospital admission through 5 years post-hospitalization
elevated native T1	percent with elevated native T1 on MRI core lab read	hospital admission through 5 years post-hospitalization
elevated extracellular volume fraction	percent with elevated extracellular volume fraction on MRI core lab read	hospital admission through 5 years post-hospitalization
coronary artery dilation	percent with coronary artery dilation on MRI core lab read	hospital admission through 5 years post-hospitalization
CMR abnormal, equivocal, or negative	final interpretation of CMR as abnormal, equivocal, or negative (i.e., no abnormal or equivocal findings) on MRI core lab read	hospital admission through 5 years post-hospitalization
Other organ abnormalities by medical history: Immunologic, rheumatologic, renal, pulmonary, hematologic, gastrointestinal, dermatologic or neurologic	percent with other organ abnormalities by medical history: Immunologic, rheumatologic, renal, pulmonary, hematologic, gastrointestinal, dermatologic or neurologic	hospital admission through 5 years post-hospitalization
CRP	C-Reactive Protein (CRP) as a laboratory marker of inflammation	hospital admission through 5 years post-hospitalization
Admission to ICU	percent with admission to ICU	hospital admission through 5 years post-hospitalization
Maximal vasoactive inotrope score	Maximal vasoactive inotrope score	from MIS-C hospital admission to MIS-C hospital discharge
Hospital length of stay	Hospital length of stay	from MIS-C hospital admission to MIS-C hospital discharge
Symptom duration	Symptom duration	hospital admission through 5 years post-hospitalization
Major medical events	percent with major medical events (e.g., stroke, need for extracorporeal therapies such as renal replacement therapy, plasma exchange, ECMO, VAD)	hospital admission through 5 years post-hospitalization
Mortality	Percent mortality	hospital admission through 5 years post-hospitalization
Global Health - FSS	Global Health as measured by Functional Status Score [FSS]: range 6-30, lower is better	hospital admission through 5 years post-hospitalization
Global Health - PROMIS	Global Health as measured by Parent-Reported Outcomes Measurement Information Systems [PROMIS] Instrument: range 7-35, higher is better	hospital admission through 5 years post-hospitalization

Collaborators and Investigators

• Sponsor: Carelon Research

Publications and helpful links

General Publications

• Lang SM, Truong DT, Powell AJ, Kazlova V, Newburger JW, Awerbach JD, Binka E, Bradford TT, Cartoski M, Cheng A, DiLorenzo MP, Dionne A, Dorfman AL, Elias MD, Garuba O, Gerardin JF, Hasbani K, Jone PN, Lam CZ, Misra N, Morgan LM, Nutting A, Patel JK, Robinson JD, Schuchardt EL, Sexson Tejtel K, Singh GK, Slesnick TC, Trachtenberg F, Taylor MD; MUSIC Study Investigators. CMR Findings in the Long-Term Outcomes After Multisystem Inflammatory Syndrome in Children (MUSIC) Study. Circ Cardiovasc Imaging. 2025 Sep;18(9):e017420. doi: 10.1161/CIRCIMAGING.124.017420. Epub 2025 Apr 4.

Study record dates

Study Major Dates

• Study Start (Actual): September 30, 2020
• Primary Completion (Estimated): July 31, 2026
• Study Completion (Estimated): July 31, 2026

Study Registration Dates

• First Submitted: February 9, 2022
• First Submitted That Met QC Criteria: March 10, 2022
• First Posted (Actual): March 18, 2022

Study Record Updates

• Last Update Posted (Actual): March 27, 2026
• Last Update Submitted That Met QC Criteria: March 26, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: COVID
• Additional Relevant MeSH Terms: Pathologic Processes; Disease; pediatric multisystem inflammatory disease, COVID-19 related
• Other Study ID Numbers: G20479

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No