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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Covid19
• Intervention / Treatment: Other: blood test

Detailed 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.

• Study Type: Observational
• Enrollment (Anticipated): 200

Contacts and Locations

• Study Contact: Name: Lucy Jones, DM (Oxon) MA BM BCh; Phone Number: 07792244418; Email: Lucy.Jones14@wales.nhs.uk

Study Locations

• United Kingdom
  • Rhondda Cynon Taf
    • Llantrisant, Rhondda Cynon Taf, United Kingdom, CF82 7XR
      • Recruiting
      • Cwm Taf Morgannwg University Health Board

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Health care workers who had a positive SARS-CoV-2 nasopharyngeal swab test more than 28 days before recruitment

Description

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.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Other

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: Cwm Taf University Health Board (NHS)
• Collaborators: Cardiff University; University of Oxford

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2020
• Primary Completion (Anticipated): October 1, 2023
• Study Completion (Anticipated): December 1, 2023

Study Registration Dates

• First Submitted: January 25, 2021
• First Submitted That Met QC Criteria: January 25, 2021
• First Posted (Actual): January 28, 2021

Study Record Updates

• Last Update Posted (Actual): May 31, 2022
• Last Update Submitted That Met QC Criteria: May 25, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19
• Other Study ID Numbers: CT 269506

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No