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

NCT ID: NCT04364828

Last Updated: 2023-11-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

1000 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-10-21

Study Completion Date

2023-08-31

Brief Summary

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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 .

Detailed Description

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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).

Conditions

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COVID-19

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

DIAGNOSTIC

Blinding Strategy

NONE

Study Groups

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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.

Group Type OTHER

Whole Genome Analysis

Intervention Type GENETIC

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.

Group Type OTHER

T-cell receptor (TCR) repertoire

Intervention Type GENETIC

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.

Group Type OTHER

SARS-CoV-2 viral composition

Intervention Type GENETIC

Determined by Next Generation sequencing

Interventions

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Whole Genome Analysis

Whole Genome Analysis with whole transcriptome analysis and deoxyribonucleic acid (DNA) methylation analysis using Methylation beadchip (EPIC) arrays

Intervention Type 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

Intervention Type GENETIC

SARS-CoV-2 viral composition

Determined by Next Generation sequencing

Intervention Type GENETIC

Eligibility Criteria

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Inclusion Criteria

* COVID-19 infection confirmed
* COVID-19 disease manifestation
* Age \> 18 years

Exclusion Criteria

* Missing informed consent of the patient/ legal guardian/ relatives
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University Hospital Tuebingen

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Olaf Rieß, Prof. Dr.

Role: STUDY_DIRECTOR

University Hospital Tübingen

Locations

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University Hospital Tübingen

Tübingen, , Germany

Site Status

Countries

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Germany

Other Identifiers

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COVID-19 NGS

Identifier Type: -

Identifier Source: org_study_id