Immune Responsiveness in Long COVID

Long COVID is a heterogenous condition. Given the dysregulated inflammation that often accompanies SARS CoV2 infection, it is likely that in some people symptoms are caused by a failure to resolve inflammation. To this end we have demonstrated persistent differences in immunity up to 12 months after acute infection. There is an expansion in terminally differentiated T effector memory cells in long COVID compared to people who make a full recovery and healthy controls. However, there is ariability and not all long COVID patients exhibit this shift in immunity. This studentship will establish if these changes delineate a subset of patients. We will establish whether there are functional differences in people with different T cell effector memory populations and whether re-challenge with SARS CoV2 antigens in the context of vaccination alters symptom burden in long COVID patients with a high T cell effector memory phenotype. Using the Virax biolabs test will enable a high throughput means for us to test a large cohort of patients with long COVID, but will also provide a diagnostic test with translational appeal for identifying people with long COVID that have a persistent change in immunity. Objective 1 will include high dimensional T cell analysis by CyTOF to distinguish long COVID patients with a high T cell terminally differentiated effector memory population (TEMRA). Objective 2 will use the Virax biolabs test to stimulate PBMCs and measure cytokine production (including Interferon gamma and IL-10). In Objective 3 we will monitor response to vaccination in different subsets of patients.