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

University Hospital Tuebingen

Status: Completed

Conditions: COVID-19

Treatments: Genetic: SARS-CoV-2 viral composition; Genetic: Whole Genome Analysis; Genetic: T-cell receptor (TCR) repertoire

Study type: Interventional

Funder types: Other

Identifiers

NCT04364828

COVID-19 NGS

Details and patient eligibility

About

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 .

Full 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).

Enrollment: 1,000 patients

Sex: All

Ages: 18+ years old

Volunteers: No 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

Trial design

Primary purpose: Diagnostic

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

---

1,000 participants in 3 patient groups

Host Genome Analysis

Other group

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.

Treatment:

Genetic: Whole Genome Analysis

Host Response to SARS-CoV-2 Infection

Other group

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.

Treatment:

Genetic: T-cell receptor (TCR) repertoire

Viral Sequence Composition

Other group

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.

Treatment:

Genetic: SARS-CoV-2 viral composition