Comparative analysis between STANDARD‐E Covi‐FERON ELISA with pre‐existing IFN‐γ release assays and determination of the optimum cutoff value for assessment of T‐Cell response to SARS‐CoV‐2

BACKGROUND: Interferon‐gamma (IFN‐γ) release assays (IGRAs) are useful for the assessment of the T‐cell response to severe acute respiratory syndrome‐coronavirus‐2 (SARS‐CoV‐2). We aimed to assess the performance of the newly developed IGRA ELISA test compared to the pre‐existing assays and to validate the cutoff value in real‐world conditions. METHODS: We enrolled 219 participants and assessed agreement between STANDARD‐E Covi‐FERON ELISA with Quanti‐FERON SARS‐CoV‐2 (QFN SARS‐CoV‐2), as well as with T SPOT Discovery SARS‐CoV‐2 based on Cohen's kappa‐index. We further determined the optimal cutoff value for the Covi‐FERON ELISA according to the immune response to vaccinations or infections. RESULTS: We found a moderate agreement between Covi‐FERON ELISA and QFN SARS‐CoV‐2 before vaccination (kappa‐index = 0.71), whereas a weak agreement after the first (kappa‐index = 0.40) and second vaccinations (kappa‐index = 0.46). However, the analysis between Covi‐FERON ELISA and T SPOT assay demonstrated a strong agreement (kappa‐index >0.7). The cut‐off value of the OS (original spike) marker was 0.759 IU/mL with a sensitivity of 96.3% and specificity of 78.7%, and that of the variant spike (VS) marker was 0.663 IU/mL with a sensitivity and specificity of 77.8% and 80.6%, respectively. CONCLUSION: The newly determined cut‐off value may provide an optimum value to minimize and prevent the occurrence of false‐negative or false‐positive during the assessment of T‐cell immune response using Covi‐FERON ELISA under real‐world conditions.