IFN-γ⁺ cell response and IFN-γ release concordance after in vitro SARS-CoV-2 stimulation

Healthcare workers (HCWs) are at increased risk since they are directly exposed to SARS-CoV-2-infected patients, and nevertheless, some remain without the development of anti-SARS-CoV-2 antibodies or related symptoms, suggesting less susceptibility to the infection.

This cross-sectional, case-control study aimed to compare SARS-CoV-2 T-cell response by two different technologies, the analysis of IFN-γ⁺ CD8⁺ /CD4⁺ T cells by flow cytometry and the quantification of IFN-γ release by ELISA-related assay (without cell discrimination), both after SARS-CoV-2 stimulation among uninfected and convalescent HCWs.

A high proportion of uninfected HCWs (53.8%) had pre-existing IFN-γ⁺ CD8 T-cell response after stimulation with at least one of the structural viral proteins S, M or N, while 35.9% had pre-existing IFN-γ⁺ CD4 T-cell response. This proportion was nearly or greater than 90% among convalescent HCWs. Interestingly, the magnitude of the response in uninfected was lower compared to that found in convalescent HCWs, using both methods. The concordance, quantifying the specific cellular response in convalescent HCWs, between both methods was 94.1% comparing CD8 T-cell response and 89.7% comparing CD4 T-cell response. This concordance was lower but still high in uninfected HCWs (76.5%) comparing CD8 T-cell response and 71.8% comparing CD4 T-cell response.

The good concordance between the proportion of individuals with IFN-γ release after SARS-COV-2 stimulation with the proportion of individuals with specific IFN-γ⁺ CD8/CD4 T cells found in this study drives IFN-γ release assays to be a simple and easy way to determine the protective immunity to SARS-CoV-2 in a wide population.