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

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)

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.

Study Overview

• Status: Completed
• Conditions: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2); Coronavirus Disease 2019 (COVID-19); Multisystem Inflammatory Syndrome in Children (MIS-C)
• Intervention / Treatment: Other: SARS-CoV-2 and/or MIS-C Exposure

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).

• Study Type: Observational
• Enrollment (Actual): 244

Contacts and Locations

Study Locations

• United States
  • California
    • Loma Linda, California, United States, 92354
      • Loma Linda University Health
    • Los Angeles, California, United States, 90048
      • Cedars-Sinai Medical Center
    • Los Angeles, California, United States, 91011
      • Children's Hospital Los Angeles
    • Palo Alto, California, United States, 94303
      • Lucile Packard Children's Hospital Stanford
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Children's Healthcare of Atlanta
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic Rochester
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • St. Louis Children's Hospital
  • New York
    • Bronx, New York, United States, 10467
      • Children's Hospital at Montefiore
    • Brooklyn, New York, United States, 11215
      • NewYork-Presbyterian Brooklyn Methodist Hospital
    • Flushing, New York, United States, 11355
      • NewYork-Presbyterian Queens Hospital
    • New Hyde Park, New York, United States, 11040
      • Cohen Children's Medical Center - Northwell Health
    • New York, New York, United States, 10016
      • Hassenfeld Children's Hospital at NYU Langone
    • New York, New York, United States, 10021
      • NewYork-Presbyterian Komansky Children's Hospital
    • New York, New York, United States, 10029
      • Mount Sinai Kravis Children's Hospital
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Children's 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
    • Pittsburgh, Pennsylvania, United States, 15224
      • UPMC Children's Hospital of Pittsburgh
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina, Pediatric Rheumatology
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Monroe Carell Jr. Children's Hospital at Vanderbilt

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 20 years (Child, Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

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

Description

Inclusion Criteria:

1. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) detection from a respiratory specimen, and/or
2. Meets criteria for Multisystem Inflammatory Syndrome in Children (MIS-C), and/or
3. 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.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
SARS-CoV-2 positive children; 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; This is an observational cohort study.; 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)

Collaborators and Investigators

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Collaborators: Autoimmunity Centers of Excellence; Clinical Trials in Organ Transplantation in Children
• Investigators: Study Chair: Steven A. Webber, MBChB, MRCP, Department of Pediatrics, Monroe Carell Jr. Children's Hospital at Vanderbilt; Principal Investigator: James D. Wilkinson, MD, MPH, Vanderbilt Institute for Clinical and Translational Research (VICTR); Principal Investigator: Natasha B Halasa, MD, MPH, Department of Pediatrics, Vanderbilt University Medical Center; Principal Investigator: Virginia Pascual, MD, Gale and Ira Drukier Institute for Children's Health, Weill Cornell Medicine; Principal Investigator: Betty Diamond, MD, Institute of Molecular Medicine, The Feinstein Institute for Medical Research; Principal Investigator: Ignacio Sanz, MD, Division of Rheumatology, Emory University; Principal Investigator: Olivia Martinez, PhD, Stanford University; Principal Investigator: Sheri Krams, PhD, Stanford University; Principal Investigator: Jeremy Boss, PhD, Emory University

Publications and helpful links

Helpful Links

• Clinical Trials in Organ Transplantation in Children
• Division of Allergy, Immunology and Transplantation
• National Institute of Allergy and Infection Diseases

Study record dates

Study Major Dates

• Study Start (Actual): November 19, 2020
• Primary Completion (Actual): March 3, 2023
• Study Completion (Actual): March 3, 2023

Study Registration Dates

• First Submitted: October 12, 2020
• First Submitted That Met QC Criteria: October 13, 2020
• First Posted (Actual): October 19, 2020

Study Record Updates

• Last Update Posted (Estimated): February 29, 2024
• Last Update Submitted That Met QC Criteria: February 28, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: participants <21 years of age; observational cohort study; immunological responses post infection
• Additional Relevant MeSH Terms: Pathologic Processes; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; Disease; Severe Acute Respiratory Syndrome; COVID-19; Coronavirus Infections; Syndrome
• Other Study ID Numbers: DAIT PRISM-01; NIAID CRMS ID#: 38772 (Other Identifier: DAIT NIAID)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No