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Genetic Predisposition to Severe Forms of COVID-19 (SARS-CoV2 Infection) (COVIDGEN)

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ClinicalTrials.gov Identifier: NCT04644146
Recruitment Status : Recruiting
First Posted : November 25, 2020
Last Update Posted : November 25, 2020
Sponsor:
Information provided by (Responsible Party):
Hospices Civils de Lyon

Brief 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. 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.

Condition or disease Intervention/treatment
Covid19 Genetic: GENETIC

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Study Type : Observational
Estimated Enrollment : 40 participants
Observational Model: Case-Control
Time Perspective: Retrospective
Official Title: Genetic Predisposition to Severe Forms of COVID-19 (SARS-CoV2 Infection) in Patients Without Comorbidities
Estimated Study Start Date : December 1, 2020
Estimated Primary Completion Date : June 1, 2021
Estimated Study Completion Date : December 1, 2021

Resource links provided by the National Library of Medicine


Group/Cohort Intervention/treatment
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
Genetic: GENETIC
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

CONTROL
Patients affected by SARS-CoV2, as shown by PCR and/or antigen testing diagnosis and without any or minor clinical expression
Genetic: GENETIC
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




Primary Outcome Measures :
  1. 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.


Biospecimen Retention:   Samples With DNA
DNA samples has been extracted for whole exome sequencing


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
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
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04644146


Contacts
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Contact: Alain CALENDER, MD 0033 4 27 85 66 13 alain.calender@chu-lyon.fr

Locations
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France
University Hospital LYON (Hospices Civils de LYON) Recruiting
Lyon, France, 69003
Sponsors and Collaborators
Hospices Civils de Lyon
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Responsible Party: Hospices Civils de Lyon
ClinicalTrials.gov Identifier: NCT04644146    
Other Study ID Numbers: 69HCL20_1072
First Posted: November 25, 2020    Key Record Dates
Last Update Posted: November 25, 2020
Last Verified: November 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Hospices Civils de Lyon:
Coronavirus SARS CoV2
COVID-19
genetics
predisposition
critical care
Additional relevant MeSH terms:
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COVID-19
Disease Susceptibility
Genetic Predisposition to Disease
Infections
Respiratory Tract Infections
Pneumonia, Viral
Pneumonia
Virus Diseases
Coronavirus Infections
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Lung Diseases
Respiratory Tract Diseases
Disease Attributes
Pathologic Processes