Understanding the Long-term Impact of COVID on Children and Families

SARS-CoV-2 Infection Clinical Trial

Official title:

NIH RECOVER: A Multi-site Observational Study of Post-acute Sequalae of SARS-CoV-2 Infection in Children

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05172011
• Other study ID #: 21-01231
• Status: Recruiting
• Start date: March 1, 2022
• Est. completion date: May 23, 2025

Study information

• Verified date: March 2024
• Source: NYU Langone Health
• Contact: Stuart Katz, MD, MS
• Phone: 1-833-422-6819
• Email: Stuart.Katz[@]nyulangone.org
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This is a combined retrospective and prospective, longitudinal, observational meta-cohort of individuals age 0-25 years who will enter the cohort with and without SARS-CoV-2 infection at varying stages before and after infection. Individuals with and without SARS-CoV-2 infection and with or without PASC symptoms will be followed to identify risk factors and occurrence of PASC. This study will be conducted in the United States and participants will be recruited through inpatient, outpatient, and community-based settings. Study data including age, demographics, social determinants of health, medical history, vaccination history, details of acute SARS-CoV-2 infection, overall health and physical function, and PASC symptoms will be reported by participants or collected from the electronic health record using a case report form at specified intervals. Biologic specimens will be collected at specified intervals, with some tests performed in local clinical laboratories and others performed by centralized research centers or banked in the Biospecimen Repository. Advanced clinical examinations and radiologic examinations will be performed at local study sites with cross-site standardization.

Description:

Ambidirectional longitudinal meta-cohort study (combined retrospective and prospective) with nested case-control studies.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 39000
• Est. completion date: May 23, 2025
• Est. primary completion date: April 1, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: N/A to 25 Years

Eligibility

Inclusion Criteria:

Infected Cohort:

Patients will be eligible for inclusion according to the following criteria:

1. Ages newborn-25 years

2. Infected individuals will have suspected, probable, or confirmed SARS-CoV-2 infection as defined by WHO criteria within 24 months of enrollment or have been born to a mother meeting these criteria during pregnancy (congenitally exposed)

3. Children/young adults with or without history of MIS-C are eligible

4. Children/young adults with or without history of SARS-CoV-2 vaccination are eligible

5. Children/young adults with evidence of past SARS-CoV-2 infection based on serum antibody profile are eligible (with or without history of acute symptoms)

6. Children/young adults with recurrent SARS-CoV-2 infections and those with post-vaccination (breakthrough) infections are eligible to participate

7. Participants are eligible without exclusion related to sex, race/ethnicity, geography, nationality, severity of disease, or underlying health conditions

Children/Young Adults with Suspected SARS-Cov-2 Infection

Children/young adults who meet these clinical criteria:

At least one of these clinical criteria:

• Acute onset of fever and cough OR

• Acute onset of ANY THREE OR MORE of the following signs or symptoms: fever, cough, general weakness /fatigue, headache, myalgia, sore throat, coryza, dyspnea, anorexia/nausea/vomiting, diarrhea, altered mental status.

AND at least one of these epidemiological criteria:

1. Residing or working in an area with a high risk of transmission of virus: closed residential, school or camp settings anytime within the 14 days before symptom onset; OR

2. Residing or travel to an area with community transmission anytime within the 14 days before symptom onset; OR

3. Any known household contact or any member of the household working in any health care setting, including within health facilities or within the community; anytime within the 14 days before symptom onset.

4. A patient with history of severe acute respiratory illness (SARI):

• SARI: acute respiratory infection with history of fever or measured fever of = 38 C°; and cough; with onset within the last 10 days; and requires hospitalization

5. An asymptomatic person not meeting epidemiologic criteria with a positive SARS-CoV-2 Antigen-RDT.

Children/Young Adults with Probable SARS-Cov-2 Infection

1. A patient who meets clinical criteria above AND is a contact of a probable or confirmed case or linked to a COVID-19 cluster; OR

2. A suspect case with chest imaging showing findings suggestive of COVID-19 disease; OR

3. A person with recent onset of anosmia (loss of smell) or ageusia (loss of taste) in the absence of any other identified cause

Children/Young Adults with Confirmed SARS-Cov-2 Infection

1. A person with a positive Nucleic Acid Amplification Test (NAAT); OR

2. A person with a positive SARS-CoV-2Antigen-RDT AND meeting either the probable case definition or suspect criteria A OR B; OR

3. An asymptomatic person with a positive SARS-CoV-2 Antigen-RDT who is a contact of a probable or confirmed case

Children/Young Adults with Asymptomatic SARS-CoV-2 Infection

1. A person without history of acute COVID-19 symptoms who has one or more of the epidemiological exposures for suspected infection and who also meets criteria b or c for suspected or probable infection, or who meets any of the criteria for confirmed infection

2. A person without history of acute COVID-19 symptoms who has positive nucleocapsid antibody test result in medical history or Tier 1 testing with or without NAAT or RDT testing or known contact to a probable or confirmed case.

Non-Infected Cohort

A person who meets the following criteria will qualify for enrollment as a non-infected control subject:

1. Does not meet WHO criteria for a suspected, probable, or confirmed case of SARS-CoV-2 infection AND

2. Does not have serological evidence of past asymptomatic SARS-CoV-2 infection in medical history or Tier 1 testing, AND

3. Lives in the same communities or recruited from the same sources as those in the SARS-CoV-2 infected cohort, AND

4. Either not hospitalized for any reason in prior 3 months, or hospitalized (with or without ICU stay) within the prior 3 months

5. Uninfected individuals may participate independent of their vaccination status

6. Uninfected individuals who develop SARS-CoV-2 infection during the study period will be reassigned to the SARS-Cov-2 infected group and will be considered to have been enrolled prior to SARS-CoV-2 infection.

Children (=3 years of age) born in and out of the context of maternal SARS-CoV-2 infection during pregnancy.

1. Children =3 years of age born to a childbearing parent with history of suspected, probable, or confirmed SARS-COV-2 infection during pregnancy (according the same criteria listed for the infected child cohort) will be enrolled in the study from existing research cohorts at the maternal fetal medicine sites in the RECOVER. network.

2. Children =3 years of age born to a childbearing parent without history of SARS-COV-2 infection during pregnancy (according to the same criteria listed for the non-infected child cohort) will also be enrolled from the same existing research cohorts at maternal fetal medicine sites in the RECOVER network.

Children with MIS-C

Children/young adults with SARS-CoV-2 infection who have history of MIS-C meeting the CDC definition:

1. An individual aged <21 years presenting with fever*, laboratory evidence of inflammation**, and evidence of clinically severe illness requiring hospitalization, with multisystem (>2) organ involvement (cardiac, renal, respiratory, hematologic, gastrointestinal, dermatologic or neurological); AND

2. No alternative plausible diagnoses; AND

3. Positive for current or recent SARS-CoV-2 infection by RT-PCR, serology, or antigen test; or exposure to a suspected or confirmed COVID-19 case within the 4 weeks prior to the onset of symptoms.

• Fever >38.0°C for =24 hours, or report of subjective fever lasting =24 hours **Including, but not limited to, one or more of the following: an elevated C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), fibrinogen, procalcitonin, d-dimer, ferritin, lactic acid dehydrogenase (LDH), or interleukin 6 (IL-6), elevated neutrophils, reduced lymphocytes and low albumin Young adults with past history of MIS-C with current ages 22-25 years are eligible to participate.

Children/Young Adults with Post-Vaccine Myocarditis

1. Age 3-25 years

2. Recipient of mRNA COVID-19 vaccination within last 4 weeks

3. Children or young adults with or without history of SARS-CoV-2 infection are eligible

4. Children or young adults with or without history of MIS-C are eligible (if any prior MIS-C-related cardiac abnormalities are known to have resolved pre-vaccination)

5. No other known auto-immune or other immune dysregulation disease

6. Participants are eligible without exclusion related to sex, race/ethnicity, geography, nationality, severity of disease, or underlying health conditions

7. Clinical evidence of probable or confirmed myocarditis based on the following criteria:

Children and young adults ages 3-25 years with presence of =1 new or worsening of the following clinical symptoms:

• chest pain, pressure, or discomfort

• dyspnea, shortness of breath, or pain with breathing

• palpitations

• syncope

OR, children aged 3-12 years might instead have =2 of the following symptoms:

• irritability

• vomiting

• poor feeding

• tachypnea

• lethargy AND

=1 new finding of:

• troponin level above upper limit of normal (any type of troponin)

• abnormal electrocardiogram (ECG or EKG) or rhythm monitoring findings consistent with myocarditis

• abnormal cardiac function or wall motion abnormalities on echocardiogram

• cardiac MRI findings consistent with myocarditis

• histopathologic confirmation of myocarditis (Definite myocarditis)¶ AND

• No other identifiable cause of the symptoms and finding

Entry criteria are adapted from the CDC definition based on the assumptions that COVID-19 vaccines will be available in the future to children <5 years of age.

Primary Caregiver Entry Criteria

1. A primary caregiver is defined as an individual, such as a family member (biological or nonbiological) or legal guardian, who is responsible for the care of the enrolled child and resides in the same household as the child. When possible, the primary caregiver identified at study entry will remain in the same role throughout the study.

2. The primary caregiver is the caregiver who spends the most time with the child or young adult, has substantial responsibility for taking care of him/her on a daily basis, and is most knowledgeable about him/her.

3. If two or more persons share equally in the caregiver responsibilities for the child or young adult, the person selected by the family to fill out study forms both about themselves and the child will be considered the primary caregiver.

4. If a biological family member primary caregiver has not reached the legal age of majority in their jurisdiction, the parent/legal guardian for the minor primary caregiver will provide consent for participation, with assent provided by the minor caregiver.

5. A nonbiological primary caregiver or legal guardian serving as primary caregiver must be above the legal age of majority in their jurisdiction.

6. The primary caregiver cannot be a babysitter or other childcare provider who receives money to care for the child.

Biological Parent Entry Criteria

• If the primary caregiver is a biological parent of the child or young adult who is participating in the study, the other biological parent may be enrolled to provide a home sample of saliva for DNA analysis.

Exclusion Criteria

An individual who meets any of the following criteria will be excluded from participation in this study:

1. Any child, young adult, caregiver, or other biological parent who in the opinion of the site investigator may be at increased risk of adverse events during participation in the study, or who may not be able to complete study procedures due to co-morbid disease or disability.

2. Any young adult age above the age of majority who lacks capacity to provide consent

3. Nonviable neonates and neonates of uncertain viability as determined by the treating physician

4. Any child, young, adult, or caregiver with co-morbid illness with expected survival <2 years

5. Any child who is being given up for adoption or is a ward of the state

6. Any caregiver or other biological parent who is incarcerated, or who lacks capacity to provide consent

7. Currently enrolled in the study Understanding the Long-term Impact of COVID-19 in Adults

Related Conditions & MeSH terms

• COVID-19
• Infections
• SARS-CoV-2 Infection

Locations

Country	Name	City	State
United States	University of New Mexico Health Sciences Center	Albuquerque	New Mexico
United States	Johns Hopkins University	Baltimore	Maryland
United States	Louisiana State University (LSU) - Pennington Biomedical Research Center	Baton Rouge	Louisiana
United States	University of Alabama at Birmingham (Pregnancy Cohort)	Birmingham	Alabama
United States	Harvard Medical School	Boston	Massachusetts
United States	Harvard School Of Public Health	Boston	Massachusetts
United States	Mass General Brigham - Harvard University	Boston	Massachusetts
United States	Northeastern University	Boston	Massachusetts
United States	University of Vermont (UVM) Children's Hospital	Burlington	Vermont
United States	University of North Carolina (UNC) at Chapel Hill	Chapel Hill	North Carolina
United States	Medical University of South Carolina (MUSC)	Charleston	South Carolina
United States	Good Samaritan Hospital	Cincinnati	Ohio
United States	Metrohealth System	Cleveland	Ohio
United States	The MetroHealth System (Pregnancy Cohort)	Cleveland	Ohio
United States	University Hospitals MacDonald's Women's Hospital	Cleveland	Ohio
United States	The Ohio State University - Wexner Medical Center	Columbus	Ohio
United States	Miami Valley Hospital	Dayton	Ohio
United States	Central Michigan University - College of Medicine	Detroit	Michigan
United States	Duke University Medical Center	Durham	North Carolina
United States	Northwestern University	Evanston	Illinois
United States	Children's Mercy Hospital	Fairfield	Ohio
United States	University of Texas Medical Branch (UTMB) Galveston	Galveston	Texas
United States	Northshore University HealthSystem	Glenview	Illinois
United States	Prisma Health Upstate	Greenville	South Carolina
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	Connecticut Children's Medical Center	Hartford	Connecticut
United States	Kapi'olani Medical Center for Women & Children	Honolulu	Hawaii
United States	Baylor College of Medicine	Houston	Texas
United States	University of Texas Health Science Center at Houston	Houston	Texas
United States	American Academy of Pediatrics	Itasca	Illinois
United States	University of California San Diego	La Jolla	California
United States	American Academy of Family Physicians	Leawood	Kansas
United States	Dartmouth-Hitchcock	Lebanon	New Hampshire
United States	Arkansas Children's Hospital and Research Institute	Little Rock	Arkansas
United States	Children's Hospital Los Angeles	Los Angeles	California
United States	University of Louisville - Norton Children's Hospital	Louisville	Kentucky
United States	Medical College Of Wisconsin	Milwaukee	Wisconsin
United States	West Virginia University	Morgantown	West Virginia
United States	Rutgers University	New Brunswick	New Jersey
United States	Saint Peter's University Hospital	New Brunswick	New Jersey
United States	Yale School of Medicine (YSM)	New Haven	Connecticut
United States	Tulane University	New Orleans	Louisiana
United States	Columbia University	New York	New York
United States	Columbia University (Pregnancy)	New York	New York
United States	NYU Langone Health	New York	New York
United States	ChristianaCare Health System	Newark	Delaware
United States	University of Oklahoma Health Sciences Center (OUHSC)	Oklahoma City	Oklahoma
United States	University Of Nebraska Medical Center	Omaha	Nebraska
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	University of Pittsburgh Medical Center (UPMC)	Pittsburgh	Pennsylvania
United States	Rhode Island Hospital	Providence	Rhode Island
United States	Women & Infants Hospital	Providence	Rhode Island
United States	NewYork-Presbyterian Hospital	Queens	New York
United States	WakeMed Health & Hospitals	Raleigh	North Carolina
United States	Virginia Commonwealth University	Richmond	Virginia
United States	Mayo Clinic	Rochester	Minnesota
United States	University of Utah Health	Salt Lake City	Utah
United States	University of California San Diego Health - Rady Children's Hospital	San Diego	California
United States	University of California San Francisco	San Francisco	California
United States	University of California San Francisco (Pregnancy Cohort)	San Francisco	California
United States	Avera Research Institute	Sioux Falls	South Dakota
United States	New York Medical College	Valhalla	New York
United States	George Washington University	Washington	District of Columbia
United States	The Pediatric Specialty Center at Saint Barnabas	West Orange	New Jersey
United States	Nemours Children's Health	Wilmington	Delaware

Sponsors (2)

Lead Sponsor	Collaborator
NYU Langone Health	National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Caregiver SARS-CoV-2 Infection Status	Initial SARS-CoV-2 infection is reported via remote patient report (electronic, paper or telephone assessments) and EHR. Infection categories include: SARS CoV 2 PCR result, SARS CoV 2 antigen result, SARS CoV 2 antibody result, SARS CoV 2 sequencing performed, diagnosed by a doctor based on symptoms, suspected by participant but not diagnosed by a doctor.	Baseline
Primary	Child SARS-CoV-2 Infection Status	Initial SARS-CoV-2 infection is reported via remote patient report (electronic, paper or telephone assessments) and EHR. Infection categories include: SARS CoV 2 PCR result, SARS CoV 2 antigen result, SARS CoV 2 antibody result, SARS CoV 2 sequencing performed, diagnosed by a doctor based on symptoms, suspected by participant but not diagnosed by a doctor.	Baseline
Primary	Caregiver Severity of SARS-CoV-2 Infection	Severity levels are reported via remote patient report (electronic, paper or telephone assessments) and EHR. NIH severity levels include: asymptomatic or presymptomatic, mild illness, moderate illness, severe illness, and critical illness.	Baseline
Primary	Child Severity of SARS-CoV-2 Infection	Severity levels are reported via remote patient report (electronic, paper or telephone assessments) and EHR. NIH severity levels include: asymptomatic or presymptomatic, mild illness, moderate illness, severe illness, and critical illness.	Baseline
Primary	Caregiver Previous In-Hospital SARS-CoV-2 Treatment Record	Treatments will be reported via remote patient report (electronic, paper, or telephone assessment) and EHR -- Treated with corticosteroids , Treated with hydroxychloroquine, Treated with lopinavir, ritonavir, other antiviral, Treated with monoclonal antibody, Treated with therapeutic anticoagulation, Treated with antibiotics.	Baseline
Primary	Child Previous In-Hospital SARS-CoV-2 Treatment Record	Treatments will be reported via remote patient report (electronic, paper, or telephone assessment) and EHR -- Treated with corticosteroids , Treated with hydroxychloroquine, Treated with lopinavir, ritonavir, other antiviral, Treated with monoclonal antibody, Treated with therapeutic anticoagulation, Treated with antibiotics.	Baseline
Primary	Caregiver Symptoms	Symptoms will be reported via remote patient report, in-person patient report, or EHR	Baseline, up to Month 48
Primary	Child Symptoms	Symptoms will be reported via remote patient report, in-person patient report, or EHR -- symptoms include: Nasal Congestion, Trouble breathing, Pain when breathing, Chest pain, Palpitations/heart racing, Dizziness/lightheadedness, Fainting, Change in hearing/ringing in ears, Blurred vision, Change in smell, Change in taste, Problems with teeth or gums, Tremors/shakiness, Feeling off-balance or unsteady, Feeling tingling or "pins and needles", Seizures/fits, Muscle weakness, Difficulty sleeping, Excessive sleepiness, Fatigue/Low energy, Feeling exhausted after walking, Poor appetite, Stomach pains/cramps, Nausea, Vomiting, Diarrhea, Constipation, Problems with urination, Skin rash, Problems with memory, Problems with concentration, Speech difficulty, Anxiety, Depression, Body pain, Headache, Problems swallowing or chewing, Change in menstruation	Baseline, up to Month 48
Primary	Caregiver SARS-CoV-2 Vaccination Status	Vaccination in status will be reported via remote patient report, in-person patient report, or EHR.	Baseline, up to Month 48
Primary	Change in Child SARS-CoV-2 Vaccination Status	Vaccination in status will be reported via remote patient report, in-person patient report, or EHR.	Week 8, up to Month 48
Primary	Change in Caregiver SARS-CoV-2 Treatment Record	Treatments will be reported via remote patient report, in-person patient report, or EHR -- Treated with corticosteroids, Treated with hydroxychloroquine, Treated with lopinavir, ritonavir, other antiviral, Treated with monoclonal antibody, Treated with therapeutic anticoagulation, Treated with antibiotics.	Month 12, up to Month 48
Primary	Change in Child SARS-CoV-2 Treatment Record	Treatments will be reported via remote patient report, in-person patient report, or EHR -- Treated with corticosteroids, Treated with hydroxychloroquine, Treated with lopinavir, ritonavir, other antiviral, Treated with monoclonal antibody, Treated with therapeutic anticoagulation, Treated with antibiotics.	Week 8, up to Month 48