Genetic Risk Factors for Multi-system Inflammatory Syndrome in Children and Pediatric Post COVID Condition
Overview
- Phase
- Not Applicable
- Status
- Recruiting
- Sponsor
- Leiden University Medical Center
- Enrollment
- 400
- Locations
- 1
- Primary Endpoint
- Quantity and quality of genetic variants in immunological genes between study groups.
Overview
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.
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:
- 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
- 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
- Study Type
- Observational
- Observational Model
- Case Control
- Time Perspective
- Prospective
Eligibility Criteria
- Ages
- 0 Months to 19 Years (Child, Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Children (\<19 years) with a history of MIS-C: as defined according to WHO criteria.
- •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.
- •'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
- •No informed consent
- •Group 1 (MIS-C): no specific exclusion criteria
- •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-
- •Children with a history of MIS-C who suffer prolonged signs and symptoms will be included in the MIS-C group.
- •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.
Outcomes
Primary Outcomes
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 Outcomes
- Correlate genetic findings with clinical characteristics(2 year)
Investigators
epbuddingh
Dr. E.P. Buddingh
Leiden University Medical Center