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

NCT ID: NCT05722717

Last Updated: 2023-02-10

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 400 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2022-06-28
• Study Completion Date: 2024-01-31

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

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

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: PROSPECTIVE

Study Groups

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.

Saliva collection at home

Intervention Type: GENETIC

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.

Saliva collection at home

Intervention Type: GENETIC

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.

Saliva collection at home

Intervention Type: GENETIC

Children (with help of their parents) collect their saliva with a saliva collection kit which they send to our research center.

Interventions

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.

Intervention Type: GENETIC

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

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.

• Minimum Eligible Age: 0 Months
• Maximum Eligible Age: 19 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

ZonMw: The Netherlands Organisation for Health Research and Development

OTHER

Sponsor Role: collaborator

University Medical Center Groningen

OTHER

Sponsor Role: collaborator

UMC Utrecht

OTHER

Sponsor Role: collaborator

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

OTHER

Sponsor Role: collaborator

Leiden University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

epbuddingh

Dr. E.P. Buddingh

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Emmeline P Buddingh, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Leiden University Medical Center

Locations

Leiden University Medical Center

Leiden, South Holland, Netherlands

Site Status: RECRUITING

Countries

Netherlands

Central Contacts

Adam J Tulling, MD

Role: CONTACT

a.j.tulling@lumc.nl

629843439 ext. +31

Emmeline P Buddingh, MD, PhD

Role: CONTACT

E.P.Buddingh@lumc.nl

715262822 ext. +31

Facility Contacts

Adam Tulling, MD

Role: primary

a.j.tulling@lumc.nl

+31629843439

Other Identifiers

NL80853.058.22

Identifier Type: -

Identifier Source: org_study_id