Development of a T cell-based immunodiagnostic system to effectively distinguish SARS-CoV-2 infection and COVID-19 vaccination status.

Both SARS-CoV-2 infections and COVID-19 vaccines elicit memory T cell responses. Here, we report the development of 2 pools of experimentally defined SARS-CoV-2 T cell epitopes that, in combination with spike, were used to discriminate 4 groups of subjects with different SARS-CoV-2 infection and COVID-19 vaccine status. The overall T cell-based classification accuracy was 89.2% and 88.5% in the experimental and validation cohorts. This scheme was applicable to different mRNA vaccines and different lengths of time post infection/post vaccination and yielded increased accuracy when compared to serological readouts. T cell responses from breakthrough infections were also studied and effectively segregated from vaccine responses, with a combined performance of 86.6% across all 239 subjects from the 5 groups. We anticipate that a T cell-based immunodiagnostic scheme to classify subjects based on their vaccination and natural infection history will be an important tool for longitudinal monitoring of vaccinations and for establishing SARS-CoV-2 correlates of protection. [Display omitted] • A T cell-based assay allows discrimination of SARS-CoV-2 infection and vaccination • The classification scheme has high sensitivity and specificity and broad applicability • The use of SARS-CoV-2 epitope pools yield higher accuracy than serological readouts • Breakthrough infections can be effectively segregated from vaccine responses Yu et al. developed an assay using epitope pools to effectively discriminate T cell responses of subjects based on their SARS-CoV-2 infection and COVID-19 vaccination history. This T cell-based classification scheme could potentially be used as an immunodiagnostic tool for longitudinal monitoring of vaccination responses and for establishing correlates of protection. [ABSTRACT FROM AUTHOR]