Research objective: Transcriptome data from main immune cell types (monocytes, CD4+ and CD8+ T cells, B-cells, NK cells) of post-COVID patients are analyzed using STP technology. STP-activity results are interpreted in combination with clinical…
ID
Source
Brief title
Condition
- Immune disorders NEC
- Viral infectious disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Transcriptome analysis by STP technology delivers a an STP activity score for
15 STPs, for each analyzed immune cell type sample (CD4+ T-, CD8+ T-,
B-lymphocytes, NK cells, monocytes). The main study parameters are the STP
activity score of 15 STP pathways of the 5 types of immune cells. The main goal
is to compare STP activity between long-COVID and controls.
Secondary outcome
We will biologically interpretate the abnormal immune function/ STP activity
profile in individual long-COVID patients followed by identification and
description of potential STP drug targets by DCDC-Tx.
If applicable, we will assess for long-COVID subtypes, based on interpretation
of STP results (regarding differential immune cell dysfunction and treatment
targets) in combination with clinical and/or other laboratory parameters.
Several biomarkers implicated in long-COVID and related to immune dysregulation
will be measured in serum (including but not limited to) cortisol, cytokines
(primarily CCL2, CCL11, galectin-1, galectin-9, IL-6, IL-8, IL-10, CXCL10 and
sCD163 (a macrophage activation marker).
Background summary
An aberrant immune response is considered to play an important role in
post-COVID. Characterization of the immune response is an essential first step
in development of therapy. A validated unique RNA-analysis-based technology is
used to measure activity of 15 crucial cellular processes (Signal Transduction
Pathways, STPs). Preliminary results in a small study by DCDC already showed
abnormal STP activity in monocytes from post-COVID patients. The study will be
performed by the highly experienced team from Erasmus MC and DCDC, supported by
C-Support, Post-COVID-NL and Post-COVID Foundation. Information on abnormally
active STPs forms the basis for subsequent therapy development by DCDC, making
use of FDA-approved drugs (>20K). DCDC has evidence that STP technology can be
applied to identify clinically effective drugs. Information on STP technology
and publications: https://DCDC-Tx.com.
Study objective
Research objective: Transcriptome data from main immune cell types (monocytes,
CD4+ and CD8+ T cells, B-cells, NK cells) of post-COVID patients are analyzed
using STP technology. STP-activity results are interpreted in combination with
clinical parameters to define the aberrant immune response in post-COVID
patients, as basis for future drug development.
Study design
1. Selection of 25 post-COVID patients and 25 control patients recovered from
acute Covid infection, making use of the clinical patient database established
by Merel Hellemons.
Blood withdrawal at out-patient clinic. Clinical annotation of selected
patients.
2. Blood sampling from selected group at outpatient clinic. Expected sample
number: n= 50 (patients + controls), 5 immune cell types per patient, total 250
samples for analysis.
Blood sampling; immune cell separation into immune cell subsets using
FACS-based sorting : CD4+ and CD8+ T cells; NK cells, B cells, monocytes; RNA
extraction, RNAseq transcriptome measurement using Illumina NGS (alternatively
Affymetrix microarrays), sample storage.
In addition cortisol, cytokines (IL-6, IL-10, TNF-alfa, Galectin-9, CCL2,
CXCL10) and sCD163 (macrophage activation marker) will be measured in plasma.
3. STP technology analysis of transcriptome data to determine quantitative STP
activities per cell sample; identification of normal range of STP activity in
control individuals; identification of abnormal STP activity for each
individual post-COVID patient and resulting mechanism of immune system
dysfunction; identification of potential subgroups.
4. Coupling of clinical annotation to STP analysis results (immune dysfunction)
per patient. Identification of potential sybtypes (based on clinical data, STP
and other blood measurements).
Study burden and risks
The questionnaires to be completed and the blood collection as part of the
study are minimally stressful. The questionnaires can be completed at home, if
required paused and completed over a longer period of time. The blood
collection may hurt a little or cause bruising, but the collection is carried
out by an experienced researcher or doctor to ensure that it runs as smoothly
as possible. To make the visit as hassle-free as possible, the sampling
location is close to the parking garage. Wheelchairs are available.
Dr. Molewaterplein 40 40
Rotterdam 3015GD
NL
Dr. Molewaterplein 40 40
Rotterdam 3015GD
NL
Listed location countries
Age
Inclusion criteria
Long-COVID patients
• Age >= 18 years, <65 years
• Past COVID-19 diagnosis, based on
o Positive PCR
o Positive Sars-Cov2 serology
o Positive rapid antigen test
o Typical clinical syndrome during the first pandemic wave, when testing was
not possible
• Long-COVID-19 diagnosis based on World Health Organization consensus
diagnosis
(*Post COVID-19 condition occurs in individuals with a history of probable or
confirmed SARS CoV-2 infection, usually 3 months from the onset of COVID-19
with symptoms and that last for at least 2 months and cannot be explained by an
alternative diagnosis. Symptoms may be new onset following initial recovery
from an acute COVID-19 episode or persist from the initial illness. Symptoms
may also fluctuate or relapse over time)*.
o Ref
https://www.who.int/publications/i/item/WHO-2019-nCoV-Post_COVID19_condition-Cli
nical_case_definition-2021.1
• Overall functioning <70% compared to functioning prior to onset of
Long-COVID/ COVID19 infection
• Presence of post-exertional malaise
• Provided written informed consent
• Long COVID symptoms present > 6 months
Healthy controls
• Age >= 18 years, <65 years
• Past COVID-19 diagnosis, based on
o Positive PCR
o Positive Sars-Cov2 serology
o Positive rapid antigen test
o Typical clinical syndrome during the first pandemic wave, when testing was
not possible
• No clinical diagnosis of long-COVID, good recovery. Overall functioning >95%
compared to functioning prior COVID-19 infection
• Self-reported general good wellbeing
• Provided written informed consent
Exclusion criteria
Long-COVID patients
• Unable or not willing to provide written informed consent
• Unable to complete written questionnaires in Dutch
• Unable to draw blood for study purposes
• Diagnosis of dementia
• Alternative diagnosis that may explain their clinical symptoms
• Re-infection or booster vaccination with COVID-19 in the past 3 months
• Suffering from any pre-existing immune-driven disease or use of
anti-inflammatory therapy of any kind (including NSAIDs and steroids) during
the last 3 months
Healthy controls
• Unable or not willing to provide written informed consent
• Unable to complete written questionnaires in Dutch
• Unable to draw blood for study purposes
• Diagnosis of dementia
• Genetically related to participating patients (e.g.
brother/sister/parent)
• Suffering from any immune-driven disease or use of anti-inflammatory therapy
of any kind
(including NSAIDs and steroids), including during the last 3 months
• Re-infection with SARS-CoV-2 or booster vaccination in the past 3 months.
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 | NL86227.078.24 |