Characterisation of the Immune Response to SARS-CoV-2 / COVID-19

Covid19 Clinical Trial

Official title:

Characterisation of the Immune Response to SARS-CoV-2 Infection

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04729452
• Other study ID #: CT 269506
• Status: Completed
• Start date: June 1, 2020
• Est. completion date: December 1, 2023

Study information

• Verified date: May 2024
• Source: Cwm Taf University Health Board (NHS)
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Emerging clinical details of the current SARS-CoV-2 pandemic have illustrated that there are multiple clinical presentations and outcomes of this viral infection. People with an infection have been reported to have a spectrum of disease from severe acute respiratory distress requiring ventilation, to mild respiratory or gastrointestinal symptoms and asymptomatic presentations. Mechanisms explaining the heterogeneity of host response to infection are yet to be characterised.

The aim of this project is to understand the host immune response to infection with SARS-CoV-2 over time in convalescent adults, including acquired immune responses, circulating levels of immune signalling molecules, gene expression profiling in peripheral blood and to identify host genetic variants associated with disease progressions or severity. Participants will be healthcare workers who had a diagnosis of COVID-19 (confirmed by positive RT-PCR assay) more than 28 days ago and have recovered and are employed by Cwm Taf Morgannwg University health board. Samples will be processed and analysed to explore immunological, host genetic factors and virological factors that explain pathogenesis and predict outcomes of infection.

Description:

AIMS AND OBJECTIVES The objective of this project is to understand the host immune response to infection with SARS-CoV-2 over time in convalescent adults, including acquired immune responses, gene expression profiling in peripheral blood and to identify host genetic variants associated with disease progressions or severity. We would like to ascertain why different people experience different disease phenotypes with this coronavirus infection.

Our primary objective is to determine key protective cellular immune parameters (e.g. T cell responses) and confirm whether there are host genetic factors that provide protection from disease. We aim to define immunodominant SARS-CoV-2 T-cell epitopes by screening overlapping peptides from the viral proteome and mapping responses to individual COVID proteins expressed intracellularly in antigen-presenting cells (to confirm processing and presentation at the cell surface). Peptide-HLA multimers will be constructed for confirmed immunodominant responses. These reagents will allow rapid enumeration and tracking of COVID-specific T cell responses in patient samples.

Our secondary objective is to determine whether there are public (shared) T-cell receptor responses to SARS-CoV-2. We will also examine whether pre-existing T-cells responses to other viruses protect against SARS-CoV-2-induced disease (COVID-19). T-cells generated will be used to test and verify detection reagents. These reagents will be developed for various projects in Oxford University including monitoring of T-cell responses induced by COVID vaccines. We will also establish whether pre-existing cross-reactive immunity to other coronaviruses correlates with disease severity as seen with the 2009 swine flu pandemic.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 160
• Est. completion date: December 1, 2023
• Est. primary completion date: October 1, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

The study will enrol eligible participants with confirmed COVID-19 PCR-based test 28 or more days prior to recruitment and be convalescent. Participants must be 18 years old and must have the capacity to provide written consent after discussing the participant information sheet. Participants must be health care workers for Cwm Taf Morgannwg University Health board.

Exclusion Criteria:

Participants who are acutely unwell with COVID. Participants who cannot provide informed written consent. Participants who have a clear co-infection with a relevant pathogen.

Related Conditions & MeSH terms

• COVID-19
• Covid19

Intervention

Other:
• blood test
blood test to test immune response to SARS-CoV-2

Locations

Country	Name	City	State
United Kingdom	Cwm Taf Morgannwg University Health board	Llantrisant	Rhondda Cynon Taf

Sponsors (3)

Lead Sponsor	Collaborator
Cwm Taf University Health Board (NHS)	Cardiff University, University of Oxford

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Determination of key protective cellular immune parameters	Our primary objective is to determine key protective cellular immune parameters (e.g. T cell responses) and confirm whether there are host genetic factors that provide protection from disease. We aim to define immunodominant SARS-CoV-2 T-cell epitopes by screening overlapping peptides from the viral proteome and mapping responses to individual COVID proteins expressed intracellularly in antigen-presenting cells (to confirm processing and presentation at the cell surface). Peptide-HLA multimers will be constructed for confirmed immunodominant responses. These reagents will allow rapid enumeration and tracking of COVID-specific T cell responses in patient samples.	2 years
Secondary	Determination of public T-cell receptor response to SARS-CoV-2	Our secondary objective is to determine whether there are public (shared) T-cell receptor responses to SARS-CoV-2. We will also examine whether pre-existing T-cells responses to other viruses protect against SARS-CoV-2-induced disease (COVID-19). T-cells generated will be used to test and verify detection reagents. These reagents will be developed for various projects in Oxford University including monitoring of T-cell responses induced by COVID vaccines. We will also establish whether pre-existing cross-reactive immunity to other coronaviruses correlates with disease severity as seen with the 2009 swine flu pandemic.	3 years