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…
ID
Source
Brief title
Condition
- Immunodeficiency syndromes
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
- Individual analysis of immunological genes in cases only: We will restrict
our analysis to pathogenic (class 5) or likely pathogenic (class 4) variants in
genes known to be associated with monogenic inborn errors of immunity to
diagnose previously unsuspected inborn errors of immunity (IEI) in MIS-C or
post-COVID condition cases.
- Case-control study: We will 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.
Secondary outcome
We will evaluate if genetic variants correlate with clinical parameters, such
as severity of illness and response to treatment.
Background summary
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.
Study 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. We will do immunological analyses to validate the results of the
genetic study. We will evaluate if certain genetic risk factors aggregate in
specific subgroups of patients.
Study burden and risks
Results of this study are related to the target group (i.e. children with
SARS-CoV-2 infection). Children with MIS-C or post-COVID condition
participating in this study may benefit directly, if an immunological condition
is identified that warrants treatment or follow-up. Controls will not directly
benefit from this study, since genetic data from the controls is analyzed at
*group level* in the case-control study. To minimize burden we will send
participants a saliva DNA home collection kit. These can be returned by regular
mail. Samples for the immunological studies have already been collected and
stored. We may request for one additional blood sample if the stored material
is insufficient in quality or quantity and we need to validate the functional
impact of a genetic variant. If this is needed, this will only be done after
additional informed consent.
Albinusdreef 2
Leiden 2333ZA
NL
Albinusdreef 2
Leiden 2333ZA
NL
Listed location countries
Age
Inclusion criteria
1. Children with a history of MIS-C: as defined according to WHO criteria [36],
who were 0-18 at the time of MIS-C
2. 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 [37].
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.
Post-COVID condition must be diagnosed by a pediatrician.
3. *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.
Exclusion criteria
1. Group 1 (MIS-C): no specific exclusion criteria
2. 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. Patients who were not diagnosed
with Post-COVID condition by a pediatrician, but only by for example a general
practitioner, are excluded.
3. Group 3 (*exposed* control group): MIS-C or post-COVID condition; AND/OR
Moderate or severe course of COVID-19, defined as: need for supplemental oxygen
and/or intensive care admission because of COVID-19 and/or death. Children are
also excluded when they have had a vaccination against SARS-CoV-2, before their
first infection with this virus. Also, the children in de the exposed control
group are excluded when their parents/siblings (1st degree family) suffer(-ed)
from MIS-C or post-COVID condition.
Design
Recruitment
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL80853.058.22 |