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

November 28, 2023 updated by: University Hospital Tuebingen
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 .

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

1000

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
      • Tübingen, Germany, 72076
        • University Hospital Tübingen

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

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

Exclusion Criteria:

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: 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
Other: 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
Other: 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Day 1, Day 3-5, Day 7-9, 48 hours after recovery

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Day 1, Day 3-5, Day 7-9, 48 hours after recovery
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
Day 1, Day 3-5, Day 7-9, 48 hours after recovery

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital Tuebingen

Investigators

  • Study Director: Olaf Rieß, Prof. Dr., University Hospital Tübingen

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 21, 2020

Primary Completion (Actual)

April 30, 2023

Study Completion (Actual)

August 31, 2023

Study Registration Dates

First Submitted

April 22, 2020

First Submitted That Met QC Criteria

April 24, 2020

First Posted (Actual)

April 28, 2020

Study Record Updates

Last Update Posted (Actual)

November 29, 2023

Last Update Submitted That Met QC Criteria

November 28, 2023

Last Verified

November 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • COVID-19 NGS

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD 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.

IPD Sharing Supporting Information Type

  • ANALYTIC_CODE

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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