We aim to assess differences in the in vivo distribution of CD8+ T-cells in patients with proven SARS-CoV-2 presenting with lymphopenia or with normal lymphocyte counts, using [89Zr]Zr-Df-IAB22M2C PET/CT imaging. Elucidating the pathophysiology…
ID
Source
Brief title
Condition
- Viral infectious disorders
- Pulmonary vascular disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The main study parameter is the whole body in vivo biodistribution of
[89Zr]Df-IAB22M2C as quantified by PET/CT. All main organs will automatically
be segmented using Siemens MIWBAS. The following parameters will be calculated
and reported in a descriptive fashion: SUVmean ±SD, SUVmax ±SD and SUVpeak
±SD, total organ activity (% of total measured activity). Statistical tests to
assess group differences will include the non-parametric Mann-Whitney U test
per organ, since normal distribution cannot be assumed. Overall distribution
profiles will be tested using Chi-square test.
Secondary outcome
Secondary endpoints:
Imaging related:
1) Spatial correlation (per lung segment) with ground-glass opacities,
consolidation and vascular thickening
Biomarker related:
2) Absolute and relative organ uptake of [89Zr]Df-IAB22M2C will be
quantitatively correlated with concurrent levels of ferritin, D-dimer, CRP, as
obtained per routine clinical care using Spearman non-parametric correlation.
3) Absolute and relative organ uptake of [89Zr]Df-IAB22M2C will be
quantitatively correlated with total lymphocyte numbers, absolute and relative
numbers of CD4+ and CD8+ T-cells using Spearman non-parametric correlation, as
well as descriptively correlated with flowcytometric markers (PD-1, TIM-3,
Granzyme B/CD127, phenotyping (CD45RA/CCR7, or CD62L/CD28) to establish
effector memory/central memory, naïve and TEMRA subsets)
Clinical outcome related:
4) Absolute and relative organ uptake of [89Zr]Df-IAB22M2C will be correlated
with the following clinical parameters: (time to) eventual ICU admission,
length of ICU stay (days), mechanical ventilation parameters, oxygen demand,
total length of hospital stay (days).
Background summary
A subset of patients diagnosed with SARS-CoV-2 infection present with
lymphopenia. The degree of lymphopenia, and in particular reduced CD8+ T-cell
numbers, is strongly correlated with clinical deterioration and ICU admission.
In contrast, general CD3-positive T-cell numbers or CD4+ T-cell numbers are
less associated.
The underlying reasons for lymphopenia in COVID-19 is currently unclear, but
several hypotheses have been put forward; 1) sequestration of CD8+ T-cells in
peripheral tissues (e.g. lung) either during the effector phase of their
lifespan or passively by local chemotactic signals, 2) accelerated maturation
and apoptosis either induced by storm of inflammatory cytokines or direct
infection or 3) resulting from decreased lymphopoiesis induced by reduced
levels of stem cell factor. The lack of data on in vivo distribution of CD8+
T-cells hampers a more thorough understanding of this critical prognostic
factor.
Study objective
We aim to assess differences in the in vivo distribution of CD8+ T-cells in
patients with proven SARS-CoV-2 presenting with lymphopenia or with normal
lymphocyte counts, using [89Zr]Zr-Df-IAB22M2C PET/CT imaging. Elucidating the
pathophysiology underlying lymphopenia at early stages of disease development
would allow to rationally design targeted interventions that aim to counteract
the detrimental effects of lymphopenia in COVID-19 patients.
Study design
This is a prospective, observational non-randomized pilot study in 20 patients
with microbiologically proven SARS-CoV-2 infection. All patients will undergo a
whole body [89Zr]Df-IAB22M2C PET/CT scan.
Study burden and risks
Toxicity tests have been performed in mice and no adverse events were seen.
Previous and published clinical studies with [89Zr]Df-IAB22M2C injection showed
no adverse events. The risks associated with the radiolabeled minibodies
injection are in general low.
PET/CT imaging with 37 MBq [89Zr]Df-IAB22M2C imposes a radiation dose
equivalent of 24 mSv to the patient. The addition of the [89Zr]Df-IAB22M2C
PET/CT scan will not cause a change in risk and will still be in the risk
category as defined by the International Commission on Radiation Protection.
Because diagnostics and treatment are not influenced by the outcome of this
study, the patient will not directly benefit from participation in this study.
For translational purposes, 10 ml EDTA blood will be drawn from an intravenous
line, prior to injection of the tracer, no additional vena puncture is needed.
Geert Grooteplein Zuid 10
Nijmegen 6525 GA
NL
Geert Grooteplein Zuid 10
Nijmegen 6525 GA
NL
Listed location countries
Age
Inclusion criteria
All patients must meet all of the following criteria:
1. microbiologically proven SARS-CoV-19 infection;
2. More than or equal to 18 years of age;
3. Ability to provide written informed consent.
Exclusion criteria
A patient will be excluded from participation in the trial if one or more of
the following criteria are met:
1. Contra-indication for PET; pregnancy, breast-feeding, severe claustrophobia
2. Contra-indication for administration of iodine-containing contrast agents
3. Other serious illness, e.g. history of malignancies or auto-immune disorders
4. Known pre-existing lymphopenia from an unrelated other medical condition
5. Estimated creatinine clearance <= 30mL/min according to the Cockcroft-Gault
formula (or local institutional standard method) OR oligo-uric patients
(<400mL/24hr)
Design
Recruitment
Medical products/devices used
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 |
|---|---|
| EudraCT | EUCTR2020-005984-29-NL |
| CCMO | NL76248.091.20 |