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

Primary Purpose

COVID-19

Status
Recruiting
Phase
Not Applicable
Locations
Germany
Study Type
Interventional
Intervention
Whole Genome Analysis
T-cell receptor (TCR) repertoire
SARS-CoV-2 viral composition
Sponsored by
University Hospital Tuebingen
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for COVID-19 focused on measuring COVID-19, SARS-CoV-2, Next-Generation-Sequencing, Whole Genome Analysis, MultiOmics, Extreme phenotypes

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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

Exclusion Criteria:

  • Missing informed consent of the patient/ legal guardian/ relatives

Sites / Locations

  • University Hospital TübingenRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Other

Other

Other

Arm Label

Host Genome Analysis

Host Response to SARS-CoV-2 Infection

Viral Sequence Composition

Arm Description

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.

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.

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.

Outcomes

Primary Outcome Measures

Viral evolution
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

Immune response
CD4+ and CD8+ T cells from blood (per µl) at different time points measured
Disease severity
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

Full Information

First Posted
April 22, 2020
Last Updated
May 17, 2022
Sponsor
University Hospital Tuebingen
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1. Study Identification

Unique Protocol Identification Number
NCT04364828
Brief Title
NGS Diagnostic in COVID-19 Hosts - Genetic Cause Relating to the Course of Disease Progression
Acronym
COVID-19 NGS
Official Title
NGS Diagnostic in COVID-19 Hosts - Genetic Cause Relating to the Course of Disease Progression
Study Type
Interventional

2. Study Status

Record Verification Date
May 2022
Overall Recruitment Status
Recruiting
Study Start Date
October 21, 2020 (Actual)
Primary Completion Date
April 2023 (Anticipated)
Study Completion Date
August 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital Tuebingen

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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 .
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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
COVID-19
Keywords
COVID-19, SARS-CoV-2, Next-Generation-Sequencing, Whole Genome Analysis, MultiOmics, Extreme phenotypes

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Not Applicable
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
1000 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Host Genome Analysis
Arm Type
Other
Arm Description
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.
Arm Title
Host Response to SARS-CoV-2 Infection
Arm Type
Other
Arm Description
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.
Arm Title
Viral Sequence Composition
Arm Type
Other
Arm Description
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.
Intervention Type
Genetic
Intervention Name(s)
Whole Genome Analysis
Intervention Description
Whole Genome Analysis with whole transcriptome analysis and deoxyribonucleic acid (DNA) methylation analysis using Methylation beadchip (EPIC) arrays
Intervention Type
Genetic
Intervention Name(s)
T-cell receptor (TCR) repertoire
Intervention Description
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
Intervention Name(s)
SARS-CoV-2 viral composition
Intervention Description
Determined by Next Generation sequencing
Primary Outcome Measure Information:
Title
Viral evolution
Description
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
Time Frame
Day 1, Day 3-5, Day 7-9, 48 hours after recovery
Secondary Outcome Measure Information:
Title
Immune response
Description
CD4+ and CD8+ T cells from blood (per µl) at different time points measured
Time Frame
Day 1, Day 3-5, Day 7-9, 48 hours after recovery
Title
Disease severity
Description
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
Time Frame
Day 1, Day 3-5, Day 7-9, 48 hours after recovery

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Olaf Rieß, Prof. Dr.
Phone
+49 (0)7071-29-
Ext
72288
Email
olaf.riess@med.uni-tuebingen.de
First Name & Middle Initial & Last Name or Official Title & Degree
Michael Bitzer, Prof. Dr.
Phone
+49 (0)7071-29-
Ext
80583
Email
m.bitzer@med.uni-tuebingen.de
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Olaf Rieß, Prof. Dr.
Organizational Affiliation
University Hospital Tübingen
Official's Role
Study Director
Facility Information:
Facility Name
University Hospital Tübingen
City
Tübingen
ZIP/Postal Code
72076
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Olaf Rieß, Prof. Dr.
Phone
+49 7071 29
Email
olaf.riess@med.uni-tuebingen.de
First Name & Middle Initial & Last Name & Degree
Michael Bitzer, Prof. Dr.
Phone
+49 7071 29
Ext
80583
Email
m.bitzer@med.uni-tuebingen.de

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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.
IPD Sharing Time Frame
Data will become available after analysis and unlimited.
IPD Sharing Access Criteria
Authorized users within the participating organizations.

Learn more about this trial

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

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