Covid19COVIDGENNCT04644146
Genetic Predisposition to Severe Forms of COVID-19 (SARS-CoV2 Infection)
An observational study of Covid19, run by Hospices Civils de Lyon at 1 site in France.
Trial summary
The main objective of this part of the project is to identify the germline genetic factors which discriminate the benign and severe forms of SARS-CoV2 (CoVID-19) infection in the context of the ongoing SARS-CoV2 (HCOVID-19) epidemic. The scientific arguments of the project are described in APPENDIX. Read more about this study
- Who is it for?
- Ages 18 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Covid19
- What is being tested?
- GENETIC
- How many people
- 40 participants
- Where
- 1 siteFrance
- Study dates
- 1 Dec 2020to 1 Dec 2021
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Patients affected by COVID-10 Age: 18-70 (values included) Without any co morbidities (analysis of the clinical files in our hospital) Without any regular treatments
Who may be able to join
- Patients affected by COVID-10 Age: 18-70 (values included) Without any co morbidities (analysis of the clinical files in our hospital) Without any regular treatments
Who cannot join
- below 18yr and higher than 70yr old
- With comorbidities - ex: diabetes, obesity, hypertension, ischemic heart, neurological disorders, autoinflammatory / autoimmune diseases …
- Not agreeing the protocol (absence of informed consent)
Trial locations and contacts
1 site in 1 country.
France1 site, 1 recruiting
- Recruiting
University Hospital LYON (Hospices Civils de LYON)
Lyon, 69003
About this study
Official title: Genetic Predisposition to Severe Forms of COVID-19 (SARS-CoV2 Infection) in Patients Without Comorbidities
The main objective of this part of the project is to identify the germline genetic factors which discriminate the benign and severe forms of SARS-CoV2 (CoVID-19) infection in the context of the ongoing SARS-CoV2 (HCOVID-19) epidemic. The scientific arguments of the project are described in APPENDIX. We hypothesize that pathogenic variants in genes coding for crucial factors involved in the HOST PATHOGEN interaction could explain the susceptibility of some patients to severe disease, even in the absence of comorbidities. The challenge is to identify those of the genetic factors who may be related respiratory distress and potentially further death. Based on our previous experience in sarcoidosis, a multifactorial disease predisposing to opportunistic infections, we will focus particularly the regulation of apoptosis and autophagy, immune response to viral infection, and endoplasmic reticulum stress response (ER STRESS) which is closely linked to apoptosis. Genetic defects in such pathways may decrease the clearance of viral particles and induces the progressive invasion by SARS-CoV2 and destruction of lung parenchyma. Our strategy will be similar to that described in our previous studies on sarcoidosis, recently published. We will combine a comparative genotype analysis by WHOLE EXOME SEQUENCING (WES) of benign and severe forms of SARS-CoV2 infection through clinical subgroups defined by the infectious diseases experts and a bioinformatics analysis of the functional networks identified by the panel of genes sharing pathogenic variants and discriminating the severe forms of the diseases. WES data will be carefully analyzed and related to all the intracellular physiological process and also the functional pathways involved in host-pathogen interaction: viral targets on the cell surface and downstream signaling, viral genomic RNA replication and translation, production and release of new viral particles. Finally, our main objectives are the definition of a gene panel more specifically related to severe forms of infection and the characterization of defective pathways involved in pejorative forms of SARS-COv2 disease in order to identify putative therapeutic targets.
- Conditions
- Covid19
- Being tested
- GENETIC
- Keywords
- Coronavirus SARS CoV2, COVID-19, genetics, predisposition, critical care
- Medical subject headings
- COVID-19, Disease Susceptibility
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GENETICGenetic
It is a retrospective study on patients which has been hospitalized since the beginning of the COVID-19 pandemic in Lyon (march 2020). The blood samples have been collected I the frame of the regular follow-up of the patients and DNA extracted and conserved for the various research protocols ongoing in the University Hospital. The DNA will be analyzed by next generation sequencing
| Study group | Role | What they receive |
|---|---|---|
| SEVERE | Patients affected by SARS-CoV2 infection with severe lung dysfunction needing oxygen complementation and critical care supports - criteria 18-70yr old and without any comorbidities Receives: Genetic: GENETIC | |
| CONTROL | Patients affected by SARS-CoV2, as shown by PCR and/or antigen testing diagnosis and without any or minor clinical expression Receives: Genetic: GENETIC |
What is being measured
The primary outcome is the main question the study is designed to answer.
Primary criteria of data evaluation
Number of genes affected by pathogenic variants in the SEVERE GROUP and for which no mutations have been observed in the CONTROL group For each gene sharing variants in the SEVERE GROUP and not in CONTROLS, the protein encoded by this gene will be identified and his function analyzed in the frame of various protein network software. The frequency of each mutation, so called the minor allele frequency will be evaluated in order to highlight only those which are rare (MAF < 0,01) in the normal population and thus suggesting a putative pathogenic role in the response to SARS-CoV2 infection.
Measured: through study completion, average 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Nov 2020
- Study start1 Dec 2020 (estimated)
- Primary completion1 Jun 2021 (estimated)
- Study completion1 Dec 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Covid19Studies of the same condition, open and under way.
- More trials run by Hospices Civils de LyonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Retrospective
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hospices Civils de Lyon
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04644146
- Sponsor's protocol ID
- 69HCL20_1072
- Acronym
- COVIDGEN
- Status last verified
- Nov 2020
- First submitted
- 19 Nov 2020
- Last updated
- 25 Nov 2020
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 25 Nov 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Genetic Predisposition to Severe Forms of COVID-19 (SARS-CoV2 Infection) in Patients Without Comorbidities
- ClinicalTrials.gov ID
- NCT04644146
- Acronym / sponsor ID
- COVIDGEN / 69HCL20_1072
- Conditions
- Covid19
- Keywords
- Coronavirus SARS CoV2, COVID-19, genetics, predisposition, critical care
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Hospices Civils de LyonUniversity, hospital or other
- Study start
- 1 Dec 2020 (estimated)
- Primary completion
- 1 Jun 2021 (estimated)
- Study completion
- 1 Dec 2021 (estimated)
- First posted
- 25 Nov 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The main objective of this part of the project is to identify the germline genetic factors which discriminate the benign and severe forms of SARS-CoV2 (CoVID-19) infection in the context of the ongoing SARS-CoV2 (HCOVID-19) epidemic. The scientific arguments of the project are described in APPENDIX. We hypothesize that pathogenic variants in genes coding for crucial factors involved in the HOST PATHOGEN interaction could explain the susceptibility of some patients to severe disease, even in the absence of comorbidities. The challenge is to identify those of the genetic factors who may be related respiratory distress and potentially further death. Based on our previous experience in sarcoidosis, a multifactorial disease predisposing to opportunistic infections, we will focus particularly the regulation of apoptosis and autophagy, immune response to viral infection, and endoplasmic reticulum stress response (ER STRESS) which is closely linked to apoptosis. Genetic defects in such pathways may decrease the clearance of viral particles and induces the progressive invasion by SARS-CoV2 and destruction of lung parenchyma. Our strategy will be similar to that described in our previous studies on sarcoidosis, recently published. We will combine a comparative genotype analysis by WHOLE EXOME SEQUENCING (WES) of benign and severe forms of SARS-CoV2 infection through clinical subgroups defined by the infectious diseases experts and a bioinformatics analysis of the functional networks identified by the panel of genes sharing pathogenic variants and discriminating the severe forms of the diseases. WES data will be carefully analyzed and related to all the intracellular physiological process and also the functional pathways involved in host-pathogen interaction: viral targets on the cell surface and downstream signaling, viral genomic RNA replication and translation, production and release of new viral particles. Finally, our main objectives are the definition of a gene panel more specifically related to severe forms of infection and the characterization of defective pathways involved in pejorative forms of SARS-COv2 disease in order to identify putative therapeutic targets.
Study design
- Observational model
- Case-control
- Time perspective
- Retrospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| SEVERE | – | Genetic: GENETICPatients affected by SARS-CoV2 infection with severe lung dysfunction needing oxygen complementation and critical care supports - criteria 18-70yr old and without any comorbidities |
| CONTROL | – | Genetic: GENETICPatients affected by SARS-CoV2, as shown by PCR and/or antigen testing diagnosis and without any or minor clinical expression |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Patients affected by COVID-10 Age: 18-70 (values included) Without any co morbidities (analysis of the clinical files in our hospital) Without any regular treatments
Key inclusion criteria (1 listed)
- Patients affected by COVID-10 Age: 18-70 (values included) Without any co morbidities (analysis of the clinical files in our hospital) Without any regular treatments
Key exclusion criteria (3 listed)
- below 18yr and higher than 70yr old
- With comorbidities - ex: diabetes, obesity, hypertension, ischemic heart, neurological disorders, autoinflammatory / autoimmune diseases …
- Not agreeing the protocol (absence of informed consent)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GENETICIt is a retrospective study on patients which has been hospitalized since the beginning of the COVID-19 pandemic in Lyon (march 2020). The blood samples have been collected I the frame of the regular follow-up of the patients and DNA extracted and conserved for the various research protocols ongoing in the University Hospital. The DNA will be analyzed by next generation sequencing | Genetic | CONTROL, SEVERE |
Primary outcome
Primary criteria of data evaluation
Time frame: through study completion, average 6 months
Number of genes affected by pathogenic variants in the SEVERE GROUP and for which no mutations have been observed in the CONTROL group For each gene sharing variants in the SEVERE GROUP and not in CONTROLS, the protein encoded by this gene will be identified and his function analyzed in the frame of various protein network software. The frequency of each mutation, so called the minor allele frequency will be evaluated in order to highlight only those which are rare (MAF < 0,01) in the normal population and thus suggesting a putative pathogenic role in the response to SARS-CoV2 infection.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Nov 2020.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Covid19, run by Hospices Civils de Lyon at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 25 Nov 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Alain CALENDER, MD (0033 4 27 85 66 13, alain.calender@chu-lyon.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Primary criteria of data evaluation (time frame: through study completion, average 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Nov 2020.