Introduction
Understanding the longevity of the adaptive immune response to SARS-CoV-2 is critical for devising public health policies to prevent reinfection. The ability to accurately measure the protective endurance of both memory B and T cells is fundamental to this understanding. Concerns about rapidly waning antibody levels post viral clearance have been raised 1. However, T cell responses may be more robust and longer lived 2. Initial studies revealed that virus-specific T cell responses developed in nearly all individuals with confirmed SARS-CoV-2 infection 3-6, with responses persisting for at least six months post-infection7, 8. Once vaccination programmes were established, vaccine-induced T cell responses could be investigated. Early studies demonstrated that SARS-CoV-2 vaccines were efficient at generating broad, protective T cell responses 9-12. Little is known about the longevity of these responses and simple methods for accurately screening viral specific T cell responses at a population level are needed to assess long term vaccine efficacy. Traditional methods of measuring T cell responses are time consuming, difficult to standardise, and require specialised equipment and technical knowledge. Moreover, current commercial tests, such as ELISpot, solely measure T cell production of interferon-gamma (IFN-γ), although other cytokines may provide better indication of anti-viral responses7. Simple, ‘rapid’ tests using whole blood, similar to those routinely used for diagnosis of tuberculosis provide an alternative approach to measure viral specific T cell responses13-15. Here, we adapted and optimised an in vitro whole blood stimulation assay to determine the most accurate biomarkers for identifying the presence of SARS-CoV-2-specific T cells in naturally infected individuals and in two cohorts of individuals pre- and post-vaccination. The high specificity and sensitivity of the test distinguishes individuals with either natural and/or vaccine induced T cell immunity from those individuals with no immunity to SARS-CoV-2.