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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.
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.
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| 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 |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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children and young adults <21 years with Multisystem Inflammatory Syndrome in Children associated with COVID-19 (MIS-C) at a participating hospital
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Alabama | Tuscaloosa | Alabama | 35401 | United States | ||
| Phoenix Children's Hospital |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 40181776 | Derived | 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. |
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Blood or saliva that is collected for future whole genome sequencing will be requested as optional at any time that the patient is undergoing a clinical laboratory draw in participants who provide consent for this testing. To better understand the genetic variation within the heterogenous MIS-C population, blood or saliva samples from the biological parents of MIS-C patients will also be requested as optional. Samples from parents will also be stored at the similar venue for future whole genome sequencing. In addition, the study investigators expect to collaborate with centers or networks that are collecting research samples on these patients.
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 |
| Phoenix |
| Arizona |
| 85016 |
| United States |
| Children's Hospital Los Angeles | Los Angeles | California | 90027 | United States |
| Valley Children's Healthcare and Hospital | Madera | California | 93636 | United States |
| UC San Diego, Rady Children's Hospital | San Diego | California | 92131 | United States |
| Children's Hospital of Colorado | Aurora | Colorado | 80045 | United States |
| The Nemours Foundation | Wilmington | Delaware | 19808 | United States |
| Children's National Hospital | Washington D.C. | District of Columbia | 20010 | United States |
| Joe DiMaggio Children's Hospital | Hollywood | Florida | 33021 | United States |
| Nicklaus Children's Hospital | Miami | Florida | 33155 | United States |
| Chldren's Healthcare of Atlanta | Atlanta | Georgia | 30322 | United States |
| Ann & Robert Lurid Children's Hospital of Chicago | Chicago | Illinois | 60611 | United States |
| Riley Children's Hospital | Indianapolis | Indiana | 46202 | United States |
| Children's Hospital of New Orleans | New Orleans | Louisiana | 70118 | United States |
| Boston Children's Hospital | Boston | Massachusetts | 02115 | United States |
| CS Mott Children's Hospital/University of Michigan | Ann Arbor | Michigan | 48109 | United States |
| Children's Hospital of Michigan | Detroit | Michigan | 48201 | United States |
| University of Mississippi | Jackson | Mississippi | 39216 | United States |
| Children's Mercy Hospital | Kansas City | Missouri | 64108 | United States |
| Morgan Stanley Children's Hospital of New York | New York | New York | 10032 | United States |
| Cohen Children's Medical Center | Queens | New York | 11040 | United States |
| University of North Carolina | Chapel Hill | North Carolina | 27514 | United States |
| Duke Children's Hospital and Health Center | Durham | North Carolina | 27705 | United States |
| Cincinnati Children's Hospital Medical Center | Cincinnati | Ohio | 45229 | United States |
| Children's Hospital of Philadelphia | Philadelphia | Pennsylvania | 19104 | United States |
| Medical University of South Carolina | Charleston | South Carolina | 29425 | United States |
| Dell Medical Center | Austin | Texas | 78707 | United States |
| Children's Medical Center of Dallas - UT Southwestern Medical Center | Dallas | Texas | 75235 | United States |
| Baylor /Texas Children's Hospital | Houston | Texas | 77030 | United States |
| Primary Children's Hospital | Salt Lake City | Utah | 84113 | United States |
| Seattle Children's Hospital | Seattle | Washington | 98105 | United States |
| Medical College of Wisconsin/Children's Hospital of Wisconsin | Milwaukee | Wisconsin | 53226 | United States |
| The Hospital for Sick Children | Toronto | Ontario | Canada |
| ID | Term |
|---|---|
| C000705967 | pediatric multisystem inflammatory disease, COVID-19 related |
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