Clinical performance of a standardized SARS-CoV-2 interferon-γ release assay for simple detection of T-cell responses after infection or vaccination

Abstract

Background

We evaluated a standardized interferon-γ (IFN-γ) release assay (IGRA) for detection of T-cell immune response after SARS-CoV-2 infection or vaccination.

Methods

This prospective study included COVID-19 patients with different severity of illness and follow-up (FU), vaccinated subjects, and healthy unvaccinated persons. SARS-CoV-2 T-cell response was measured using a specific quantitative IGRA in whole blood (Euroimmun, Germany) and TrimericS-IgG and neutralizing antibodies with validated serological platforms. Positivity of RT‐PCR or vaccination was considered as reference standard.

Results

Two hundred and thirty nine individuals were included (152 convalescent, 54 vaccinated and 33 uninfected unvaccinated). Overall sensitivity, specificity, positive (PPV) and negative (NPV) predictive values (95% CI) of the IGRA were 81.1% (74.9%‐86%), 90.9% (74.5%‐97.6%), 98.2% (94.5%‐99.5%), and 43.5% (31.8%‐55.9%), respectively. All vaccinated SARS-CoV-2-naïve subjects had positive IGRA at 3 months. In convalescent subjects the magnitude of IFN-γ responses and IGRA accuracy varied according to disease severity and duration of FU, with the best performance in patients with severe COVID-19 at 3-month and the worst in those with mild disease at 12-month. The greatest contribution of IGRA to serological tests was observed in patients with mild disease and long-term FU (incremental difference, 30.4%).

Conclusion

The IGRA assessed was a reliable method of quantifying T-cell response after SARS-COV-2 infection or vaccination. In convalescent patients the sensitivity is largely dependent on disease severity and time since primary infection. The assay is more likely to add clinical value to serology in patients with mild infections.