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Genetic Risk Factors for Multi-system Inflammatory Syndrome in Children and Pediatric Post COVID Condition (GRIP)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05722717
Recruitment Status : Recruiting
First Posted : February 10, 2023
Last Update Posted : February 10, 2023
Sponsor:
Collaborators:
ZonMw: The Netherlands Organisation for Health Research and Development
University Medical Center Groningen
UMC Utrecht
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Information provided by (Responsible Party):
epbuddingh, Leiden University Medical Center

Study Description
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Brief Summary:
We will perform Whole Exome Sequencing on DNA from saliva. We will include: Children with a history of MIS-C; children with post-COVID condition; and controls in order to identify rare, high impact genetic variants in immunological genes and pathways in children with a history of MIS-C or pediatric post-COVID condition.

Condition or disease Intervention/treatment
COVID-19 Post-Acute COVID-19 Post-Acute COVID19 Syndrome Multi-System Inflammatory Syndrome in Children Pediatric Inflammatory Multisystem Syndrome Post COVID-19 Condition Post-COVID-19 Syndrome Genetic: Saliva collection at home

Detailed Description:

Rationale:

Following infection with SARS-CoV-2, some children develop the potentially life-threatening disease Multi-System Inflammatory Syndrome in Children (MIS-C) and some children develop post-COVID condition (formerly 'long COVID'). It is unknown why some children develop severe or prolonged symptoms after SARS-CoV-2 infection, while most children have asymptomatic or mild disease. We hypothesize that rare variants in genes associated with the immune system predispose children to develop MIS-C or post-COVID condition after infection with SARS-CoV-2.

Objective:

Primary objective: To identify rare, high impact genetic variants in immunological genes and pathways in children with a history of MIS-C or pediatric post-COVID condition.

Secondary objectives: To analyze the clinical characteristics and long-term effects of pediatric COVID-19 and MIS-C. To characterize the functional and clinical impact of genetic variants in MIS-C and post-COVID condition and identify targets for therapy.

Study design:

We will do an observational study. We will perform Whole Exome Sequencing (WES) using Next Generation Sequencing (NGS) on DNA from blood or saliva. We will include: (1) MIS-C cases: Children with a history of MIS-C; (2) post-COVID condition cases: Children with post-COVID condition; and (3) Controls: SARS-CoV-2 exposed age-matched control group: children who were infected with SARS-CoV-2 but did not develop moderate to severe COVID-19, MIS-C or post-COVID condition.

Study population:

Children 0-19 years old with a history of MIS-C (n=100), post-COVID condition (n=100), or uncomplicated SARS-CoV-2 infection (n=200).

Main study parameters/endpoints:

  1. To evaluate if some children with MIS-C or post-COVID condition have an inborn error of immunity by determining the presence of pathogenic or likely pathogenic variants in immunological genes
  2. To evaluate if a larger proportion of cases with MIS-C or post-COVID condition have rare and presumably deleterious variants in immunological genes than children with an asymptomatic or mild infection
Study Design
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Study Type : Observational
Estimated Enrollment : 400 participants
Observational Model: Case-Control
Time Perspective: Prospective
Official Title: Genetic Risk Factors for Multi-system Inflammatory Syndrome in Children and Pediatric Post COVID Condition
Actual Study Start Date : June 28, 2022
Estimated Primary Completion Date : January 31, 2024
Estimated Study Completion Date : January 31, 2024

Resource links provided by the National Library of Medicine


Groups and Cohorts
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Group/Cohort Intervention/treatment
MIS-C
Children with a history of MIS-C: as defined according to WHO criteria, who were 0-18 at the time of MIS-C.
 Genetic: Saliva collection at home
Children (with help of their parents) collect their saliva with a saliva collection kit which they send to our research center.
Post COVID-Condition
Children with post-COVID condition who were 0-18 at the time of SARS-CoV-2 infection: as defined according to the WHO case definition.
 Genetic: Saliva collection at home
Children (with help of their parents) collect their saliva with a saliva collection kit which they send to our research center.
Control
'Exposed' control group: children with a history of proven SARS-CoV-2 infection (RT-PCR, antigen test or serology positive) who were 0-18 at the time of SARS-CoV-2 infection.
 Genetic: Saliva collection at home
Children (with help of their parents) collect their saliva with a saliva collection kit which they send to our research center.


Outcome Measures
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Primary Outcome Measures :
  1. Quantity and quality of genetic variants in immunological genes between study groups. [ Time Frame: 2 year ]
    We want to quantify how many immunogenic variants are found between the groups and identify which variants/genes these are.


Secondary Outcome Measures :
  1. Correlate genetic findings with clinical characteristics [ Time Frame: 2 year ]
    We want to connect the data found during genetic testing with multiple clinical characteristics already collected in previous studies.


Biospecimen Retention:   Samples With DNA
Saliva

Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   0 Months to 19 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
Children with a history of MIS-C or Post-COVID Condition and children with a known SARS-CoV-2 infection without severe disease course.
Criteria

Inclusion Criteria:

  1. Children (<19 years) with a history of MIS-C: as defined according to WHO criteria.
  2. Children (<19 years) with post-COVID condition: as defined according to the WHO case definition. This includes a history of probable or confirmed prior SARS-CoV-2 infection, with signs and symptoms (including fatigue, shortness of breath, cognitive dysfunction) that are present after 12 weeks, last at least 2 months, have an impact on daily functioning and are not explained by an alternative diagnosis.
  3. 'Exposed' control group: children (<19 years of age): a history of proven SARS-CoV-2 infection (RT-PCR, antigen test or serology positive). If the child has been vaccinated against SARS-CoV-2, the first documented infection must have been prior to the vaccination.

Exclusion Criteria:

  1. No informed consent
  2. Group 1 (MIS-C): no specific exclusion criteria

  3. Group 2 (post-COVID condition): other plausible cause of symptoms AND/OR a history compatible with chronic fatigue syndrome prior to infection with SARS-CoV-2.

    Children with a history of MIS-C who suffer prolonged signs and symptoms will be included in the MIS-C group.

  4. Group 3 ('exposed' control group): MIS-C or post-COVID condition; AND/OR Moderate or severe course of COVID-19, as defined in the COPP-study (N20.043) (need for supplemental oxygen and/or intensive care admission because of COVID-19 and/or death) AND/OR first degree relative with long COVID or MIS-C.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05722717


Contacts
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Contact: Adam J Tulling, MD 629843439 ext +31 a.j.tulling@lumc.nl
Contact: Emmeline P Buddingh, MD, PhD 715262822 ext +31 E.P.Buddingh@lumc.nl

Locations
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Netherlands
Leiden University Medical Center Recruiting
Leiden, Zuid-Holland, Netherlands, 2333ZA
Contact: Adam Tulling, MD    +31629843439    a.j.tulling@lumc.nl   
Sponsors and Collaborators
Leiden University Medical Center
ZonMw: The Netherlands Organisation for Health Research and Development
University Medical Center Groningen
UMC Utrecht
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Investigators
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Principal Investigator: Emmeline P Buddingh, MD, PhD Leiden University Medical Center
More Information
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Responsible Party: epbuddingh, Dr. E.P. Buddingh, Leiden University Medical Center
ClinicalTrials.gov Identifier: NCT05722717    
Other Study ID Numbers: NL80853.058.22
First Posted: February 10, 2023    Key Record Dates
Last Update Posted: February 10, 2023
Last Verified: February 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by epbuddingh, Leiden University Medical Center:
COVID-19
Post-COVID Condition
MIS-C
PIMS-TS
Additional relevant MeSH terms:
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COVID-19
Post-Acute COVID-19 Syndrome
Syndrome
Disease
Pathologic Processes
Pneumonia, Viral
Pneumonia
Respiratory Tract Infections
Infections
Virus Diseases
 Coronavirus Infections
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Lung Diseases
Respiratory Tract Diseases
Post-Infectious Disorders
Chronic Disease
Disease Attributes