The purpose of this study is to learn about the safety and effects of the vaccine (called COMIRNATY) for the potential prevention of COVID-19. This study is seeking participants who: 1. Are age \<21 years. 2. Have presentation to participating medical center with evaluation in Emergency Room and/or hospitalization. 3. Received any dose(s) of COMIRNATY within 21 days of symptom onset. 4. Meet criteria of Centers for Disease Control and Prevention case definition of probable or confirmed myocarditis/pericarditis 5. Are capable of giving signed informed consent/assent (by parents/legal guardians of minors and/or patients), which includes compliance with the requirements and restrictions listed in the Informed Consent/Assent Document and in this protocol OR meets criteria for waiver of consent. This study will examine the potential long-term effects associated with myocarditis/pericarditis following vaccination with COMIRNATY. The association of myocarditis/pericarditis in participants who received the study vaccine (COMIRNATY) compared with those associated with COVID-19 will also be examined. This will help us determine if COMIRNATY is safe and effective, and if there is a myocarditis/pericarditis association that should be noted. Participants will take part in this study for up to 5 years. During this time, they will receive complete cardiac imaging tests, and have follow up visits per guidance stated in the study protocol.
This is a low-interventional cohort study to determine cardiac and non-cardiac long-term outcomes of persons \<21 years of age with myocarditis/pericarditis after the administration of COMIRNATY, compared with similarly aged persons with myocarditis/pericarditis associated with COVID-19, including MIS-C. To be classified as having COMIRNATY-associated myocarditis/pericarditis, a person must 1) meet the CDC case definition for probable or confirmed myocarditis/pericarditis, 2) have received any dose of COMIRNATY ≤ 21 days of symptom onset, and 3) have no other plausible alternative etiology at the time of enrollment. To be classified as having myocarditis/pericarditis associated with COVID-19, a person must have 1) either acute severe COVID-19 infection or MIS-C, as defined by the CDC, 2) findings of probable or confirmed myocarditis in the CDC definition, 3) no other plausible alternative etiology. A description of the three cohorts is as follows: Cohort 1: Prospectively ascertained cases of probable or confirmed myocarditis/pericarditis associated with COMIRNATY , i.e., participants enrolled under protocol during hospitalization or \</= 2 weeks of hospital discharge. Cohort 2: Retrospectively ascertained cases of probable or confirmed myocarditis/pericarditis associated with COMIRNATY , i.e., participants enrolled \> 2 weeks after hospital discharge. Participants can be retrospectively ascertained and enrolled at any time from their COMIRNATY-associated myocarditis/pericarditis. Cohort 3: Comparator cohort of COVID-19- related myocarditis/pericarditis , including MIS-C, both retrospectively and prospectively ascertained, and enrolled at any time from their COVID-19 or MIS-C associated myocarditis/pericarditis diagnosis. Cohort 3 participants will not be stratified by MIS-C diagnosis because of the rarity of myocardial involvement in children with acute severe COVID-19 Participants in all cohorts will be those who present to participating medical centers for care. This study is a collaboration between the National Heart, Lung, and Blood Institute (NHLBI)'s Pediatric Heart Network (PHN) and Pfizer. Enrollment will include approximately 200 prospectively and retrospectively ascertained cases of children, adolescents, and young adults \<21 years of age who receive care for myocarditis/pericarditis associated with COMIRNATY (Cohort 1 and 2); and approximately 100 persons \<21 years of age with COVID -19-associated myocarditis/pericarditis, including MIS-C (Cohort 3).
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
OTHER
Masking
NONE
Enrollment
319
ECG, echocardiogram, ambulatory monitor, exercise stress test
Childrens Hospital Los Angeles
Los Angeles, California, United States
Valley Children's Hospital
Madera, California, United States
Connecticut Children's Medical Center
Hartford, Connecticut, United States
Childrens National Hospital
Washington D.C., District of Columbia, United States
Memorial Healthcare System
Hollywood, Florida, United States
Children's Healthcare of Atlanta - Arthur M. Blank Hospital
Atlanta, Georgia, United States
Indiana University School of Medicine
Indianapolis, Indiana, United States
Riley Hospital for Children at IU Health
Indianapolis, Indiana, United States
Children's Hospital
New Orleans, Louisiana, United States
Boston Children's Hospital
Boston, Massachusetts, United States
...and 8 more locations
Composite findings of myocarditis
This is a single composite primary outcome measure. This primary composite study endpoint is defined as the presence of 1 or more of the following 6 months after illness onset: left ventricular dysfunction (LVEF \< 55% by echocardiogram), findings of myocarditis by original or revised Lake Louise criteria on cardiac MRI, or the presence of high-grade arrhythmia or conduction system disturbance on ECG or ambulatory monitoring.
Time frame: 6 months after illness onset
Left ventricular ejection fraction (LVEF) < 55% by echocardiography
Time frame: Up to 5 years following illness onset.
Myocarditis by original or revised Lake Louise criteria on cMRI
Time frame: Up to 5 years following illness onset.
Arrhythmias on cardiac recording (ECG, ambulatory monitoring)
Time frame: Up to 5 years following illness onset.
Complications, including non-cardiac morbidities by medical history
Time frame: Up to 5 years following illness onset.
Functional Status by Behavior Assessment System for Children, Third Edition BASC-3 or PROMIS Short Forms
Behavior Assessment System for Children, Third Edition (BASC-3), \<8 yr (T score \<30-\>70 with higher number meaning lower functioning) or PROMIS Short Forms ≥8 yr (scores from 3-15 with higher number meaning better functioning)
Time frame: Up to 5 years following illness onset.
The Pediatric Quality of Life Inventory (PEDS QL)
The 27 question, age-appropriate and parent-proxy questionnaires, will be used in 2 to \<18-year-old participants to assess quality of life. Scores span 0-108 with higher number being better functioning.
Time frame: Up to 5 years following illness onset.
The Quality of Life Scale (QOLS)
The QOLS, a 16-item self-report form that assesses overall quality of life on a scale of 16-112 (higher scores indicate better quality of life) will be administered for participants ≥18 years old.
Time frame: Up to 5 years following illness onset.
Conduction system disturbances on cardiac recording (ECG, ambulatory monitoring)
Time frame: Up to 5 years following illness onset.
Left ventricular ejection fraction (LVEF) by echocardiogram as a measure of myocardial performance.
Time frame: During the hospitalization or within 2 weeks of hospital discharge, generally obtained less than 3 weeks from presentation.
Time to recovery of myocardial inflammation and injury by Lake Louise (the original or revised) criteria
Time frame: During hospitalization or within 2 weeks of hospital discharge, commonly less than 3 weeks from presentation
Arrhythmias on cardiac recording (ECG, ambulatory monitoring)
Time frame: During hospitalization or within 2 weeks of hospital discharge, commonly less than 3 weeks from presentation
Complications, including non-cardiac morbidities for myocarditis
Time frame: During hospitalization or within 2 weeks of hospital discharge, commonly less than 3 weeks from presentation
Echocardiographic LVEF
Time frame: Up to 5 years following illness onset.
Myocardial inflammation scarring (by cMRI)
Time frame: Up to 5 years following illness onset.
Arrhythmias on cardiac recordings
Time frame: Up to 5 years following illness onset.
Complications, including non-cardiac morbidities by medical history
Time frame: Up to 5 years following illness onset.
Lower LVEF by composite results
Identification of possible sociodemographic and medical risk factors for greater frequency and severity of acute and longer-term cardiac sequelae in participants, measured by ECG, original or revised Lake Louise criteria on cMRI, and presence of high-grade arrhythmia or conduction system disturbance on ECG or ambulatory monitoring.
Time frame: Up to 5 years following illness onset.
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For patients with isolated pericarditis, to determine time to recovery to normal.
Freedom from 1. symptoms/signs of pericarditis; 2. typical ECG findings of pericarditis; 3. \>small pericardial effusion; 4. therapy with anti-inflammatory medications
Time frame: At each study visit, up to 5 years, until the endpoint event is met
Conduction system disturbances on cardiac recording (ECG, ambulatory monitoring)
Time frame: During hospitalization or within 2 weeks of hospital discharge, commonly less than 3 weeks from presentation
Conduction system disturbances on cardiac recordings
Time frame: Up to 5 years following illness onset.
Freedom from the primary study endpoint ((The Primary Study Endpoint is the Composite Findings of Myocarditis and is described in Outcome Measure 1).
Measurement Schedule and Type of Assessment: 1. Echocardiography: 2 weeks, 6 weeks, 6 months , and 1-5 years; 2. cMRI: If ordered for routine clinical care, 6 months; annually at 1-5 years if previous study was abnormal; 3. Exercise stress testing by 6 months; annually at 1-5 years if previous study was abnormal
Time frame: 2 weeks, 6 weeks, 6 months, and 1-5 years
Time to recovery (return to normal) from the presence of abnormal LV strain parameters on echocardiography among those who had abnormalities at baseline
Time frame: 2 weeks, 6 weeks, 6 months, and 1-5 years