Clinical trial NCT04588363: COVID-19: Pediatric Research Immune Network on SARS-CoV-2 and MIS-C
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)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)
Multisystem Inflammatory Syndrome in Children (MIS-C)
Coronavirus Disease 2019 (COVID-19)
Keywords: participants <21 years of age
observational cohort study
immunological responses post infection
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: Autoimmunity Centers of Excellence
name: Clinical Trials in Organ Transplantation in Children
First posted: 2020-10-19
Enrollment: 244
Sex: ALL
Maximum age (years): 20
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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

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).

Eligibility criteria: 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.

Primary outcomes:
measure: 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
timeFrame: 6 Months Post Illness Presentation (Enrollment)
Secondary outcomes:
measure: 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
timeFrame: 1 Year Post Illness Presentation (Enrollment)
measure: All-Cause Mortality
timeFrame: 1 Year Post Illness Presentation (Enrollment)
measure: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Mortality
timeFrame: 1 Year Post Illness Presentation (Enrollment)
measure: Hospitalization for Participants Enrolled as an Outpatient or Rehospitalization after First Admission in Hospitalized Participants
timeFrame: Up to 1 Year Post Illness Presentation (Enrollment)
measure: Coagulation Abnormality by D-Dimer Biomarker
timeFrame: Up to 1 Year Post Illness Presentation (Enrollment)
measure: Coagulation Abnormality by Fibrinogen Biomarker
timeFrame: Up to 1 Year Post Illness Presentation (Enrollment)
measure: Coagulation Abnormality by Prothrombin Time (PT) and Activated Partial Thromboplastin Time (PTT) Biomarkers
timeFrame: Up to 1 Year Post Illness Presentation (Enrollment)
measure: Coagulation Abnormality by International Normalised Ratio (INR) Biomarker
timeFrame: Up to 1 Year Post Illness Presentation (Enrollment)
measure: Coronary Artery Abnormalities
timeFrame: Up to 1 Year Post Illness Presentation (Enrollment)
measure: Pulmonary Hypertension
timeFrame: Up to 1 Year Post Illness Presentation (Enrollment)
measure: Cardiovascular System Dysregulation by B-type natriuretic peptide (BNP) Biomarker
timeFrame: Up to 1 Year Post Illness Presentation (Enrollment)
measure: Cardiovascular System Dysregulation by Troponin I Biomarker
timeFrame: Up to 1 Year Post Illness Presentation (Enrollment)
measure: Cardiovascular System Dysregulation by Echocardiogram
timeFrame: Up to 1 Year Post Illness Presentation (Enrollment)
measure: Cardiovascular System Dysregulation by Electrocardiogram (ECG)
timeFrame: Up to 1 Year Post Illness Presentation (Enrollment)
measure: Pulmonary Abnormalities
timeFrame: Up to 1 Year Post Illness Presentation (Enrollment)
measure: Pulmonary Function Characteristics
timeFrame: Up to 1 Year Post Illness Presentation (Enrollment)
measure: Renal/Metabolic Biomarkers: Serum Creatinine and Blood Urea Nitrogen (BUN)
timeFrame: Up to 1 Year Post Illness Presentation (Enrollment)
measure: Renal/Metabolic Biomarker: Estimated glomerular filtration rate (eGFR)
timeFrame: Up to 1 Year Post Illness Presentation (Enrollment)
measure: Hepatic/Metabolic Biomarkers: Serum Alkaline Phosphatase (Alk Phos), Alanine Aminotransferase ( ALT/SGPT)and Aspartate Aminotransferase (AST/SGOT)
timeFrame: Up to 1 Year Post Illness Presentation (Enrollment)
measure: Hepatic/Metabolic Biomarker: Total Bilirubin
timeFrame: Up to 1 Year Post Illness Presentation (Enrollment)
measure: Neurologic Abnormalities
timeFrame: Up to 1 Year Post Illness Presentation (Enrollment)
measure: 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)
timeFrame: Up to 1 Year Post Illness Presentation (Enrollment)
measure: Health Related Quality of Life
timeFrame: Up to 1 Year Post Illness Presentation (Enrollment)
Other outcomes:
Locations:
city: Loma Linda
country: United States
facility: Loma Linda University Health
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles
state: California
city: Palo Alto
country: United States
facility: Lucile Packard Children's Hospital Stanford
state: California
city: Atlanta
country: United States
facility: Children's Healthcare of Atlanta
state: Georgia
city: Rochester
country: United States
facility: Mayo Clinic Rochester
state: Minnesota
city: Saint Louis
country: United States
facility: St. Louis Children's Hospital
state: Missouri
city: Bronx
country: United States
facility: Children's Hospital at Montefiore
state: New York
city: Brooklyn
country: United States
facility: NewYork-Presbyterian Brooklyn Methodist Hospital
state: New York
city: Flushing
country: United States
facility: NewYork-Presbyterian Queens Hospital
state: New York
city: New Hyde Park
country: United States
facility: Cohen Children's Medical Center - Northwell Health
state: New York
city: New York
country: United States
facility: Hassenfeld Children's Hospital at NYU Langone
state: New York
city: New York
country: United States
facility: NewYork-Presbyterian Komansky Children's Hospital
state: New York
city: New York
country: United States
facility: Mount Sinai Kravis Children's Hospital
state: New York
city: Durham
country: United States
facility: Duke University Children's Health Center
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Children's Hospital of Pittsburgh
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina, Pediatric Rheumatology
state: South Carolina
city: Nashville
country: United States
facility: Monroe Carell Jr. Children's Hospital at Vanderbilt
state: Tennessee
Study officials:
affiliation: Department of Pediatrics, Monroe Carell Jr. Children's Hospital at Vanderbilt
name: Steven A. Webber, MBChB, MRCP
role: STUDY_CHAIR
affiliation: Vanderbilt Institute for Clinical and Translational Research (VICTR)
name: James D. Wilkinson, MD, MPH
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Pediatrics, Vanderbilt University Medical Center
name: Natasha B Halasa, MD, MPH
role: PRINCIPAL_INVESTIGATOR
affiliation: Gale and Ira Drukier Institute for Children's Health, Weill Cornell Medicine
name: Virginia Pascual, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Institute of Molecular Medicine, The Feinstein Institute for Medical Research
name: Betty Diamond, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Division of Rheumatology, Emory University
name: Ignacio Sanz, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Stanford University
name: Olivia Martinez, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Stanford University
name: Sheri Krams, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Emory University
name: Jeremy Boss, PhD
role: PRINCIPAL_INVESTIGATOR
References: