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NGS Diagnostic in COVID-19 Hosts - Genetic Cause Relating to the Course of Disease Progression (COVID-19 NGS)

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ClinicalTrials.gov Identifier: NCT04364828
Recruitment Status : Not yet recruiting
First Posted : April 28, 2020
Last Update Posted : November 6, 2020
Sponsor:
Information provided by (Responsible Party):
University Hospital Tuebingen

Study Description
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Brief Summary:
In this study (i) the host genome to identify susceptibility regions of infection, inflammation, and host defense, (ii) host response to Severe Acute Respiratory Syndrome-Corona-Virus-2 (SARS-CoV-2) infection, and (iii) viral sequence composition to define viral sequences which may be correlated with disease severity in addition to the metagenome of the throat swab will be analysed .

Condition or disease Intervention/treatment Phase
COVID-19 Genetic: Whole Genome Analysis Genetic: T-cell receptor (TCR) repertoire Genetic: SARS-CoV-2 viral composition Not Applicable

Detailed Description:

This study aims to recruit adult persons with diagnostically confirmed Corona-Virus- Disease-19 (COVID-19) infection and with different disease manifestation who are included into diagnostic or therapeutic care at the University Hospital Tübingen (UKT).

The COVID-19 Next-Generation-Sequencing (NGS) study aims to cover as many patients in Germany as possible. It is expected to include in Phase 1 (pilot study): 250 patients with different disease manifestation (extreme phenotypes) and individual risk factors by whole genome analysis Phase 2 (verification study): 1.000 clinically well-defined patients to ensure a broader range of overlapping phenotypes, to verify data from the pilot study.

Phase 3 (confirmation study): > 10.000 patients to increase the power (anticipated).

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 1000 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: NGS Diagnostic in COVID-19 Hosts - Genetic Cause Relating to the Course of Disease Progression
Estimated Study Start Date : January 2021
Estimated Primary Completion Date : April 2022
Estimated Study Completion Date : August 2022
Arms and Interventions
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Arm Intervention/treatment
Host Genome Analysis
For 150 patients from the extreme phenotypes - complementary to Whole Genome Analysis of each patient also Whole Transcriptome will performed Analysis; DNA methylation analysis using EPIC arrays will be performed in the pilot study (phase 1). Identically, in phase 2 starting from month 4, will be generated WGS, Whole transcriptome sequencing (WTS), and methylation data of the 500 patients. Epigenetic changes are likely to occur upon Corona infection. Subsequently, genome and epigenome data with RNA expression pattern will be correlated.
 Genetic: Whole Genome Analysis
Whole Genome Analysis with whole transcriptome analysis and deoxyribonucleic acid (DNA) methylation analysis using Methylation beadchip (EPIC) arrays
Host Response to SARS-CoV-2 Infection
Focus on longitudinal analysis of TCR repertoire of CD4+ and CD8+ T cells from blood samples (PBMCs) from clinically characterized patients (n = 24). The bulk- T-cell receptor (TCR) sequencing will be performed at different time points during the course of disease progression and recovery.
 Genetic: T-cell receptor (TCR) repertoire
Longitudinal analysis of TCR repertoire of Cluster of Differentiation 4+ (CD4+) and CD8+ T cells from blood samples (Peripheral Blood Mononuclear Cells, PBMCs) from clinically characterized patients
Viral Sequence Composition
The Severe Acute Respiratory Syndrome-Corona Virus-2 (SARS-CoV-2) viral composition is determined by Next Generation sequencing (different protocols for enrichment are available, and are currently being tested to successfully analyse the virus from different isolates). It is known that SARS-CoV-2 sequence is changing at least one position every second passing from person to person. Numerous variants have been described deriving from 3 different ancestral viruses (named A, B, and C) reflecting different distributions in East Asia, Europeans and Americans. At it is anticipated that other (super)infections may add to the severity of the infection and disease course, the entire metagenome of the throat is being sequenced and analyzed as well.
 Genetic: SARS-CoV-2 viral composition
Determined by Next Generation sequencing


Outcome Measures
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Primary Outcome Measures :
  1. Viral evolution [ Time Frame: Day 1, Day 3-5, Day 7-9, 48 hours after recovery ]
    The change in the genetic makeup of a virus population (measured in numbers) as the viruses mutate and multiply over time at different time points


Secondary Outcome Measures :
  1. Immune response [ Time Frame: Day 1, Day 3-5, Day 7-9, 48 hours after recovery ]
    CD4+ and CD8+ T cells from blood (per µl) at different time points measured

  2. Disease severity [ Time Frame: Day 1, Day 3-5, Day 7-9, 48 hours after recovery ]

    Clinical classification according to severity:

    • Light and uncomplicated (mild symptoms)
    • Moderate (mild pneumonia)
    • Severe pneumonia
    • Critical (Acute Respiratory Distress Syndrome (ARDS), sepsis, septic shock) Evaluated at several time points


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • COVID-19 infection confirmed
  • COVID-19 disease manifestation
  • Age > 18 years

Exclusion Criteria:

  • Missing informed consent of the patient/ legal guardian/ relatives
Contacts and Locations
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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): NCT04364828


Contacts
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Contact: Olaf Rieß, Prof. Dr. +49 (0)7071-29- ext 72288 olaf.riess@med.uni-tuebingen.de
Contact: Michael Bitzer, Prof. Dr. +49 (0)7071-29- ext 80583 m.bitzer@med.uni-tuebingen.de

Sponsors and Collaborators
University Hospital Tuebingen
Investigators
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Study Director: Olaf Rieß, Prof. Dr. University Hospital Tübingen
More Information
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Responsible Party: University Hospital Tuebingen
ClinicalTrials.gov Identifier: NCT04364828    
Other Study ID Numbers: COVID-19 NGS
First Posted: April 28, 2020    Key Record Dates
Last Update Posted: November 6, 2020
Last Verified: April 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: The COVID-19 NGS study will provide data in a pseudonymized manner to national and international databases set up to increase the diagnostic yield through advanced analysis tools.
Supporting Materials: Analytic Code
Time Frame: Data will become available after analysis and unlimited.
Access Criteria: Authorized users within the participating organizations.

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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 University Hospital Tuebingen:
COVID-19
SARS-CoV-2
Next-Generation-Sequencing
 Whole Genome Analysis
MultiOmics
Extreme phenotypes
Additional relevant MeSH terms:
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Disease Progression
Disease Attributes
Pathologic Processes