Clinical trial NCT05722717: Genetic Risk Factors for Multi-system Inflammatory Syndrome in Children and Pediatric Post COVID Condition
Official title: Genetic Risk Factors for Multi-system Inflammatory Syndrome in Children and Pediatric Post COVID Condition
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: 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
Keywords: COVID-19
Post-COVID Condition
MIS-C
PIMS-TS
Lead sponsor: Leiden University Medical Center
Sponsor class: OTHER
Collaborators: name: ZonMw: The Netherlands Organisation for Health Research and Development
name: University Medical Center Groningen
name: UMC Utrecht
name: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
First posted: 2023-02-10
Enrollment: 400
Sex: ALL
Minimum age (years): 0
Maximum age (years): 19
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
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.

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:

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

Eligibility 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.

Primary outcomes:
measure: Quantity and quality of genetic variants in immunological genes between study groups.
timeFrame: 2 year
Secondary outcomes:
measure: Correlate genetic findings with clinical characteristics
timeFrame: 2 year
Other outcomes:
Locations:
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
state: Zuid-Holland
Study officials:
affiliation: Leiden University Medical Center
name: Emmeline P Buddingh, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: