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

COVID-19 Clinical Trial

— GRIP  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05722717
• Other study ID #: NL80853.058.22
• Status: Recruiting
• Start date: June 28, 2022
• Est. completion date: January 31, 2024

Study information

• Verified date: February 2023
• Source: Leiden University Medical Center
• Contact: Adam J Tulling, MD
• Phone: 629843439
• Email: a.j.tulling[@]lumc.nl
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 400
• Est. completion date: January 31, 2024
• Est. primary completion date: January 31, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 0 Months to 19 Years

Eligibility

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.

Related Conditions & MeSH terms

• COVID-19
• Disease
• Post-COVID-19 Syndrome
• Syndrome

Intervention

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.

Locations

Country	Name	City	State
Netherlands	Leiden University Medical Center	Leiden	Zuid-Holland

Sponsors (5)

Lead Sponsor	Collaborator
Leiden University Medical Center	Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA), UMC Utrecht, University Medical Center Groningen, ZonMw: The Netherlands Organisation for Health Research and Development

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Quantity and quality of genetic variants in immunological genes between study groups.	We want to quantify how many immunogenic variants are found between the groups and identify which variants/genes these are.	2 year
Secondary	Correlate genetic findings with clinical characteristics	We want to connect the data found during genetic testing with multiple clinical characteristics already collected in previous studies.	2 year