COVID-19: Pediatric Research Immune Network on SARS-CoV-2 and MIS-C

Study Overview
=================
Brief Summary
-----------------
The primary objectives of this study are: To determine the proportion of children with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) related death, rehospitalization or major complications after infection with SARS-CoV-2 and/or Multisystem Inflammatory Syndrome in Children (MIS-C), and To determine immunologic mechanisms and immune signatures associated with disease spectrum and subsequent clinical course during the year of follow-up.

Detailed Description
-----------------
This is a prospective, multicenter, observational cohort study to assess short and long-term clinical outcomes and immune responses after Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection and/or Multisystem Inflammatory Syndrome in Children (MIS-C) in children (e.g., defined as individuals who have not reached their 21st birthday at the time of enrollment). SARS-CoV-2 causes Coronavirus Disease 2019 (COVID-19) Participants will be identified through active recruitment measures within hospitals and through ambulatory and laboratory-based databases of SARS-CoV-2 positive individuals <21 years of age. The study will enroll a minimum of 250 subjects from a diverse racial/ethnic background, from participating medical centers in the United States. The study period of participation is 1 year (12 months).

Official Title
-----------------
An Observational Cohort Study to Determine Late Outcomes and Immunological Responses After Infection With SARS-CoV-2 in Children With and Without Multisystem Inflammatory Syndrome (MIS-C)

Conditions
-----------------
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), Multisystem Inflammatory Syndrome in Children (MIS-C), Coronavirus Disease 2019 (COVID-19)

Intervention / Treatment
-----------------
* Other: SARS-CoV-2 and/or MIS-C Exposure


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) detection from a respiratory specimen, and/or Meets criteria for Multisystem Inflammatory Syndrome in Children (MIS-C), and/or Meets criteria for MIS-C, except has involvement of only 1 organ system Cases meeting clinical criteria for MIS-C but without known SARS-CoV-2 exposure, and who are being treated as MIS-C by the treating physician, but with negative SARS-CoV-2 PCR and pending or negative antibody testing, may be enrolled as subjects. If subsequent antibody testing is positive, cases will be labelled as confirmed MIS-C. If SARS-CoV-2 antibody testing is negative, subjects will be labeled at the end of the study as suspected/not confirmed MIS-C. Exclusion Criteria: 1. Subject and/or parent/guardian who are not able to understand or be willing to provide informed consent and where applicable assent --Note, for this observational cohort study, participation in other COVID-19 studies is not an automatic exclusionary criterion.

Ages Eligible for Study
-----------------
Maximum Age: 20 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| SARS-CoV-2 positive children<br>Individuals less than 21 years of age who fulfill one or more of the following criteria: SARS-CoV-2 detection from a respiratory specimen, and/or Meets criteria for MIS-C, and/or Meets criteria for MIS-C, except has involvement of only 1 organ system | Other: SARS-CoV-2 and/or MIS-C Exposure<br>* This is an observational cohort study.<br>* Other names: Exposure: Severe Acute Respiratory Syndrome Coronavirus 2 Infection and/or Multisystem Inflammatory Syndrome in Children diagnosis;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Participants With Either COVID-19-Related Death, Rehospitalization, Major Complications after SARS-CoV-2 Illness and/or MIS-C at 6 Months Post Illness Presentation | Participants who experience Coronavirus Disease 2019 (COVID-19)-related death, rehospitalization or major complications after Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) illness and/or multisystem inflammatory syndrome in children (MIS-C). | 6 Months Post Illness Presentation (Enrollment) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Participants with Coronavirus Disease 2019 (COVID-19)-Related Death after Multisystem Inflammatory Syndrome in Children (MIS-C) at 1 Year Post Illness Presentation | Participants who experience Coronavirus Disease 2019 (COVID-19)-related death, rehospitalization or major complications after Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) illness and/or multisystem inflammatory syndrome in children (MIS-C). | 1 Year Post Illness Presentation (Enrollment) | 
| All-Cause Mortality | The occurrence of death in participants regardless of relationship to Coronavirus Disease 2019 (COVID-19) and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). | 1 Year Post Illness Presentation (Enrollment) | 
| Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Mortality | The occurrence of SARS-CoV-2 related death in participants. | 1 Year Post Illness Presentation (Enrollment) | 
| Hospitalization for Participants Enrolled as an Outpatient or Rehospitalization after First Admission in Hospitalized Participants | Characterization of Participants who require: Hospitalization subsequent to enrollment as an outpatient for SARS-CoV-2/COVID-19 related illness and/or MIS-C, or Rehospitalization after discharge from their initial admission for SARS-CoV-2/COVID-19 related illness and/or MIS-C. Abbreviations: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Coronavirus Disease 2019 (COVID-19) Multisystem Inflammatory Syndrome in Children (MIS-C) | Up to 1 Year Post Illness Presentation (Enrollment) | 
| Coagulation Abnormality by D-Dimer Biomarker | Characterization of dysregulation involving the coagulation system by D-dimer laboratory test. | Up to 1 Year Post Illness Presentation (Enrollment) | 
| Coagulation Abnormality by Fibrinogen Biomarker | Characterization of dysregulation involving the coagulation system by fibrinogen laboratory test. | Up to 1 Year Post Illness Presentation (Enrollment) | 
| Coagulation Abnormality by Prothrombin Time (PT) and Activated Partial Thromboplastin Time (PTT) Biomarkers | Characterization of dysregulation involving the coagulation system by PT and PTT laboratory tests. | Up to 1 Year Post Illness Presentation (Enrollment) | 
| Coagulation Abnormality by International Normalised Ratio (INR) Biomarker | Characterization of dysregulation involving the coagulation system by INR laboratory test. | Up to 1 Year Post Illness Presentation (Enrollment) | 
| Coronary Artery Abnormalities | Characterization of coronary artery abnormalities (e.g., by echocardiogram and, if performed for clinical indications, angiogram, as examples). | Up to 1 Year Post Illness Presentation (Enrollment) | 
| Pulmonary Hypertension | Prevalence of pulmonary hypertension by echocardiogram and standard of care assessments. | Up to 1 Year Post Illness Presentation (Enrollment) | 
| Cardiovascular System Dysregulation by B-type natriuretic peptide (BNP) Biomarker | Characterization of cardiovascular system dysregulation by BNP laboratory test. | Up to 1 Year Post Illness Presentation (Enrollment) | 
| Cardiovascular System Dysregulation by Troponin I Biomarker | Characterization of cardiovascular system dysregulation by Troponin I laboratory test. | Up to 1 Year Post Illness Presentation (Enrollment) | 
| Cardiovascular System Dysregulation by Echocardiogram | Characterization of cardiac function by echocardiogram (Echo), a test that uses high frequency sound waves (ultrasound) to make pictures of the heart. The test is also referred to as a diagnostic cardiac ultrasound. | Up to 1 Year Post Illness Presentation (Enrollment) | 
| Cardiovascular System Dysregulation by Electrocardiogram (ECG) | Characterization of cardiovascular system dysregulation(s) evaluated by standardized 12-lead electrocardiogram. ECG rhythms, intervals and voltages will be assessed. Cross reference: ECG and EKG are used interchangeably. | Up to 1 Year Post Illness Presentation (Enrollment) | 
| Pulmonary Abnormalities | Pulmonary fibrosis (i.e., scarring) or other abnormalities detected by computerized tomography (CT) imaging. | Up to 1 Year Post Illness Presentation (Enrollment) | 
| Pulmonary Function Characteristics | Characterization by pulmonary function tests (spirometry without bronchodilators). | Up to 1 Year Post Illness Presentation (Enrollment) | 
| Renal/Metabolic Biomarkers: Serum Creatinine and Blood Urea Nitrogen (BUN) | Characterization of kidney/metabolic function by serum creatinine and blood urea nitrogen (BUN) laboratory tests | Up to 1 Year Post Illness Presentation (Enrollment) | 
| Renal/Metabolic Biomarker: Estimated glomerular filtration rate (eGFR) | Characterization of kidney/metabolic function by the estimated glomerular filtration rate (eGFR) calculated value, using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. | Up to 1 Year Post Illness Presentation (Enrollment) | 
| Hepatic/Metabolic Biomarkers: Serum Alkaline Phosphatase (Alk Phos), Alanine Aminotransferase ( ALT/SGPT)and Aspartate Aminotransferase (AST/SGOT) | Characterization of liver/metabolic function by the following laboratory tests: alkaline phosphatase alanine aminotransferase (ALT/SGPT) and aspartate aminotransferase (AST/SGOT). | Up to 1 Year Post Illness Presentation (Enrollment) | 
| Hepatic/Metabolic Biomarker: Total Bilirubin | Characterization of liver/metabolic function by serum total bilirubin laboratory test. | Up to 1 Year Post Illness Presentation (Enrollment) | 
| Neurologic Abnormalities | Characterization of neurologic sequelae of infection/disease. | Up to 1 Year Post Illness Presentation (Enrollment) | 
| Other End Organ and/or functional abnormalities Occurring After Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection/ Coronavirus Disease 2019 (COVID-19) and/or Multisystem Inflammatory Syndrome in Children (MIS-C) | Identified by and characterized during standard of care assessments. | Up to 1 Year Post Illness Presentation (Enrollment) | 
| Health Related Quality of Life | Assessment of health-related quality of life (HRQOL) after Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection/ Coronavirus Disease 2019 (COVID-19) and/or multisystem inflammatory syndrome in children (MIS-C). The Pediatric Quality of Life Inventory is a series of assessment instruments designed to measure the health-related quality of life of children. The PedsQL 4.0 provides an opportunity for the assessment of both overall (generic) quality of life as well as disease-specific quality of life. The PedsQL 4.0 Generic Core Scales are appropriate for assessing health-related quality of life in both healthy and chronically ill children. The four scales making up this generic battery include Physical Functioning (8 items), Emotional Functioning (5 items), Social Functioning (5 items), and School Functioning (5 items). | Up to 1 Year Post Illness Presentation (Enrollment) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
participants <21 years of age, observational cohort study, immunological responses post infection