To assess whether premature aging of both the innate and adaptive arms of theimmune system are associated with COVID-19 morbidity and mortality. Identify immune (andendocrine) parameters that might be of use in predicting disease progression and…
ID
Source
Brief title
Condition
- Endocrine and glandular disorders NEC
- Immune disorders NEC
- Respiratory tract infections
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Cellular immune parameters
- Extensive immunophenotyping of T-lymphocyte maturation subsets, including
recently thymic emigrants
- Extensive immunophenotyping of B-lymphocyte maturation subsets
- Extensive immunophenotyping of monocyte maturation subsets
- SARS-CoV-2 specific CD8+ T cell response using immunodominant peptides that
are shared between SARS-CoV and SARS-CoV-2.
Molecular immune parameters
- Immune repertoire (T-cell receptor and B-cell receptor) sequencing, including
replication history
- Gene expression profiles related to premature immunosenescence in monocytes
- HLA-typing
Serological immune parameters
- Cytokines, for instance:
CCL2/CCL3/CCL4/CCL7/CXCL10/FASL/G-CSF/Galectin-9/GM-CSF /IFN*/IFN*/
IL-1b/IL1Ra/IL-6/IL-7/IL-8/IL-10/Il-12/IL-18/sCD163/sCD206/sIL2R/sIL6R/TNF*
- Autoantibodies, for instance: ANA/ANCA/ anti-thyroid/anti-adrenal
Serological hormonal parameters
Hormonal axis; pituitary-growth hormone axis, pituitary-thyroid axis,
pituitary-adrenal axis, pituitary-thyroid axis and sex hormone axis
Insulin/glucose ratio
Lepthin-ghrelin-adipokines
Secondary outcome
Additional genetic analysis
Exome sequencing and gene expression profiles to analyze the involved pathways
obtained from cytokine analysis, (for example IL-6 pathway associated genes and
ACE-2 associated cytokine-receptors that are shed from the plasma membrane)
Background summary
A proper functioning immune system is crucial for clearance of acute viral
infections. Ageing and obesity negatively affect immune functioning and aged or
obese humans display an insufficiently strong/delayed immune response upon
viral infection. We hypothesize, that patients that develop severe or fatal
COVID-19 have a pre-existing state of immune-ageing that prevents the
initiation and maintenance of a proper immune response against SARS-CoV2.
Study objective
To assess whether premature aging of both the innate and adaptive arms of the
immune system are associated with COVID-19 morbidity and mortality. Identify
immune (and
endocrine) parameters that might be of use in predicting disease progression
and facilitate
optimal treatment choice.
More specific objectives
We want to determine:
(i) whether signs of pre-existing ageing of the peripheral blood T-cell and
B-cell compartment
are related to COVID-19 morbidity and mortality
(ii) whether signs of pre-existing ageing of the peripheral blood monocyte
compartment are
related to COVID-19 morbidity and mortality
(iii) whether certain serological cytokine/autoantibody/hormonal profiles are
indicative of an
altered immune set-point and related to COVID-19 morbidity and mortality
Study design
A: comparative, non-randomized, observational, multi-center study
B: Observational cohort
Na-Heparin blood and serum will be obtained at the emergency
department/intensive care unit and patient stratification will be applied (see
below). From hospital admitted non-ICU and hospital admitted ICU patients
longitudinal samples obtained once weekly will be collected. Heparin blood will
be used for different types of cellular and molecular analysis, see below.
Serum will be used for extensive cytokine, autoantibody and hormonal profiling.
Study burden and risks
Risks are negligible, burden is low
Wytemaweg 80
Rotterdam 3015 CN
NL
Wytemaweg 80
Rotterdam 3015 CN
NL
Listed location countries
Age
Inclusion criteria
Suspected of COVID-19
Age * 18 years
Providing informed consent after reading patient information
Exclusion criteria
Insufficient knowledge of Dutch
No signed informed consent
Design
Recruitment
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 | NL73846.078.20 |