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.
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.
Other: blood test
blood test to test immune response to SARS-CoV-2
Other Name: serial blood tests over 6 months
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.
Cwm Taf Morgannwg University Health board
Llantrisant, Rhondda Cynon Taf, United Kingdom
Investigator: Rhian Beynon
Contact: 01443443421
Rhian.Beynon@wales.nhs.uk
Lucy Jones, DM (Oxon) MA BM BCh
07792244418
Lucy.Jones14@wales.nhs.uk