Validation and performance evaluation of a novel interferon-γ release assay for the detection of SARS-CoV-2 specific T-cell response

Huzly, D.; Panning, M.; Smely, F.; Enders, M.; Komp, J.; Steinmann, D.

Background: The reliable detection of the T-cell mediated response to COVID-19 or COVID-19 vaccination is important for individual patient care and for monitoring the immune response e.g. in COVID-19 vaccine trials in a standardized fashion. Methods: We used blood samples from health care workers (HCW) with or without history of COVID-19 to define test accuracy of a novel interferon-{gamma} release assay. Usefulness of qualitative and quantitative results after COVID-19 vaccination was examined in HCW receiving homologous or heterologous vaccination regimens. For a real-life performance evaluation, we analysed interferon-{gamma} response to complete vaccination in 149 patients receiving immunosuppressive or immune modulating therapies. Results: Using a double-cut-off strategy integrating the result of background stimulation the assay had a specificity of 100%. Sensitivity of the IGRA was 83.5 and 100% in HCW after SARS-CoV-2 infection more or less than 6 months ago. Quantitative results showed significant differences between first and second vaccine dose, but no difference between homologous and heterologous vaccination regimen. The majority of immunocompromised patients showed no immune response or isolated T-cell or antibody response to complete vaccination. Conclusions: The novel IGRA proved to be a highly specific and sensitive tool to detect the SARS-CoV-2 specific T-cell response to COVID-19 as well as COVID-19 vaccination. In perspective, it may serve as a standardized tool in COVID-19 vaccine trials and in clinical care of immunosuppressed patients.