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

NCT04364828 | Completed

• 1 other identifier: COVID-19 NGS
• Study Type: interventional
• Target: 1,000
• Locations: 1 country
• Sites: 1

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 .

Conditions

COVID-19

Keywords

COVID-19; SARS-CoV-2; Next-Generation-Sequencing; Whole Genome Analysis; MultiOmics; Extreme phenotypes

Outcome Measures

Primary Outcomes (1)

• 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

  Day 1, Day 3-5, Day 7-9, 48 hours after recovery

Secondary Outcomes (2)

• Immune response

  Day 1, Day 3-5, Day 7-9, 48 hours after recovery

• Disease severity

  Day 1, Day 3-5, Day 7-9, 48 hours after recovery

Study Arms (3)

Host Genome Analysis

OTHER

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

Host Response to SARS-CoV-2 Infection

OTHER

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

Viral Sequence Composition

OTHER

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

Interventions

Whole Genome Analysis GENETIC

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

Host Genome Analysis

T-cell receptor (TCR) repertoire 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

Host Response to SARS-CoV-2 Infection

SARS-CoV-2 viral composition GENETIC

Determined by Next Generation sequencing

Viral Sequence Composition

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• University Hospital Tuebingen: lead

Study Sites (1)

University Hospital Tübingen

Tübingen, 72076, Germany

Location

MeSH Terms

Conditions

COVID-19

Interventions

Genome-Wide Association Study; Receptors, Antigen, T-Cell

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Epidemiologic Research Design; Epidemiologic Methods; Investigative Techniques; Molecular Epidemiology; Genetic Association Studies; Genetic Techniques; Oligonucleotide Array Sequence Analysis; Sequence Analysis; Public Health; Environment and Public Health; Receptors, Antigen; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins; Proteins; Amino Acids, Peptides, and Proteins

Study Officials

• Olaf Rieß, Prof. Dr.

  University Hospital Tübingen

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 22, 2020
• First Posted: April 28, 2020
• Study Start: October 21, 2020
• Primary Completion: April 30, 2023
• Study Completion: August 31, 2023
• Last Updated: November 29, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: ANALYTIC CODE
• Time Frame: Data will become available after analysis and unlimited.
• Access Criteria: Authorized users within the participating organizations.

Locations

DE (1)