Primary objective: To obtain a detailed immunological profile of children presenting to Dutch hospitals with acute SARS-CoV-2 infection or with a SARS-CoV-2 related post-infectious inflammatory syndrome. Secondary objectives: (1) To correlate the…
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Brief title
Condition
- Immune disorders NEC
- Viral infectious disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
We will perform detailed immunological analyses in a two-tiered approach. In
the first tier we will do a rapid, more general assessment of the immune
system. This will include a detailed phenotypical analysis of the cells of the
innate and adaptive immune system using spectral flow cytometry, a multiplex
analysis of inflammatory cytokines using Luminex bead arrays and a quantitative
and qualitative analysis of anti-SARS-CoV-2 antibodies. Depending on the
results of the investigations in the first tier, we will choose which in-depth
immunological analyses will be done in the second tier. Investigations in the
second tier will focus on the innate immune system, the adaptive immune system
(either T-cell responses or B-cell responses) and/or biomarker discovery of
serum proteins.
Main study parameter/endpoints of the reinfection substudy
1. To determine the incidence rate of reinfections with SARS-CoV-2.
2. To investigate risk factors (demographic, clinical, virological,
immunological) for SARS-CoV-2 reinfections.
3. To understand which factors determine the longevity and breadth of
protective SARS-CoV-2-specific humoral immunity.
4. To determine the health impact of SARS-CoV-2 reinfections or their sequelae.
Secondary outcome
We will correlate the immunological profiles with detailed clinical outcome
measures of the patients. We will collect these clinical outcome measures in
the same manner as in our related cohort study *Clinical features of COVID-19
in Pediatric Patients* (COPP-study). Clinical parameters collected include:
severity of disease (need of supplemental oxygen); underlying illnesses; age at
presentation; clinical syndrome; laboratory parameters at diagnosis and during
illness; response to treatment; clinical outcome, and patient reported outcome
measures at 6 weeks follow-up.
Secondary study parameter/endpoints of the reinfection substudy
To determine the incidence rate of (co-)infections (such as influenza viruses
and RSV).
Background summary
The immune response of children to infection with SARS-CoV-2 is markedly
different to the immune response of adults with COVID-19. Children are less
likely to develop severe COVID-19, but some children do need supplemental
oxygen or intensive care. In rare cases, children who have been infected with
SARS-CoV-2 develop a potentially life-threatening post-infectious inflammatory
syndrome termed *multisystem inflammatory syndrome in children* (MIS-C). To
better understand and treat these severe sequelae of SARS-CoV-2 infection in
children, comprehensive immunological analysis in parallel with the collection
of detailed clinical information is needed.
For the substudy on reinfections:
Reinfections with SARS-CoV-2 occur frequently due to declining immunity after
previous infection and/or vaccination and the emergence of new virus variants
that partially circumvent existing immunity. It is currently unknown if
children with a history of severe COVID-19 and/or MIS-C are at an increased
risk of severe sequelae after reinfection. This substudy is part of a ZonMw
funded collaboration between 7 different existing COVID-19 cohorts in the
Netherlands (children and adults): *Riding the waves in the pandemic tail:
incidence, risk factors and impact of SARS-COV-2 reinfections*, or *RTW-study*.
Study objective
Primary objective: To obtain a detailed immunological profile of children
presenting to Dutch hospitals with acute SARS-CoV-2 infection or with a
SARS-CoV-2 related post-infectious inflammatory syndrome.
Secondary objectives: (1) To correlate the immunological profiles with detailed
clinical parameters. We will collect clinical data in this COPP-IMM study in
the same way as in our related observational cohort study *Clinical features of
COVID-19 in Pediatric Patients* (COPP-study). Clinical parameters include:
severity of disease, underlying illnesses, age at presentation, clinical
syndrome, laboratory parameters at diagnosis, outcome. (2) To identify
immunological targets of therapy.
Main study parameter/endpoints of the reinfection substudy
The overall aim is to to investigate risk factors, including existing
SARS-CoV-2-specific antibody and T cell immunity, and health impact of
reinfections, including the nature, severity and duration of symptoms, during
the autumn, winter and spring seasons of 2022-2023, in children previously seen
in or admitted to hospital with COVID-19 or MIS-C.
Study design
Study design: Multicenter prospective cohort study
Study burden and risks
Blood samples for this study will be collected after confirmation of the
diagnosis COVID-19 or MIS-C and after the patient and/or the caregiver have
consented for participation. The amount of blood drawn depends on the body
weight of the patient, and ranges from 5 to 50 mL. To ensure minimal burden as
possible, the collection of the blood sample will be combined with a blood
sample collection for routine clinical care and/or will be drawn from an
indwelling venous catheter, if possible. If this is not possible, a
venepuncture will be done to collect material for this study. In this case,
there will some burden to the patient. To ensure that this burden is minimal,
we will apply a topical anaesthetic (lidocaine/prilocaine or
lidocaine/tetracaine as per local guidelines) and will instruct local
researchers on positive language before and during the procedure.
The risk of this study to the participants is negligible. There is no direct
benefit of this study for the participants. The results from this study will
benefit the target group, i.e. children with COVID-19 or MIS-C, by identifying
immunological targets of therapy.
For the reinfection substudy:
The blood sampling and swabs will cause some burden. To ensure that this burden
is minimal, will use positive language before and during the sampling. The
finger will be warmed. The risk of this study to the participants is
negligible. There is no direct benefit of this study for the participants. The
results from this study will benefit the target group, i.e. children with a
history of COVID-19 or MIS-C, by identifying risk factors, clinical features
and immunological characteristics of reinfection.
Albinusdreef 2
Leiden 2333ZA
NL
Albinusdreef 2
Leiden 2333ZA
NL
Listed location countries
Age
Inclusion criteria
- age up to and including 17 years
- clinical or microbiological diagnosis of COVID-19 or MIS-C
- presentation in hospital (outpatient department, emergency department, or
clinical admission)
Study population of the substudy on reinfections: enrolled participants of the
initial studies COPP/COPP-IMM will be approached to also participate in the
current substudy.
Inclusion criteria for this substudy:
- Children with a prior COVID-19 infection and/or MIS-C, treated as in- or
outpatients in Dutch hospitals, AND
- Previously included in the COPP/COPP-IMM study between 1st of March 2020 and
1st of September 2022, with consent to be approached for subsequent studies, AND
- Informed consent for the reinfection substudy
Exclusion criteria
Age 18 years or older
No COVID-19 or MIS-C
No informed consent
For blood sampling: body weight under 3 kg
Exclusion criteria for the substudy on reinfections
A potential subject who meets any of the following criteria will be excluded
from
- No consent from guardians and/or patient
Design
Recruitment
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
Followed up by the following (possibly more current) registration
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Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL76177.058.21 |