QuantiFERON SARS-CoV-2 assay for the evaluation of cellular immunity after immunization with mRNA SARS-CoV-2 vaccines: a systematic review and meta-analysis.

A systematic review and meta-analysis were performed to evaluate the virus-specific T-cell response after COVID-19 mRNA vaccination, using the QuantiFERON SARS-CoV-2 interferon-γ release assay. A search was conducted (June 8, 2023) in the PUBMED, SCOPUS, and medRxiv databases, to identify studies reporting the QuantiFERON SARS-CoV-2 (Starter (two antigen tubes) or Starter + Extended Pack (three antigen tubes), cut-off ≥ 0.15 IU/mL) positivity rate (PR) in immunocompetent adults, following the administration of two or three COVID-19 mRNA vaccine doses. Study quality was evaluated with the Critical Appraisal Skills Programme Tool. A meta-analysis was conducted using a random-effects model. Heterogeneity and publication bias were assessed. Eleven eligible studies (with 5-73 vaccinated immunocompetent participants) were identified. For COVID-19-naïve participants, ≤ 3 months after the second dose, the pooled PR (random-effects model) was 86 (95% confidence interval (95% CI) 78-95%). Comparing the Starter vs. the Starter + Extended Pack, a significant difference in PRs was detected (80.6% vs. 100% p-value < 0.001). At 3-6 and >6 months after the second dose and ≥ 3 months after the third dose, the pooled PRs were 59% (95% CI 45-72%), 79% (95% CI 66-92%), and 66% (95% CI 50-82%), respectively. For convalescent participants, ≥ 6 months after the third dose, the pooled PR was 81% (95% CI 67-95%). Limitations include heterogeneity and a small number of studies, at some timepoints. In conclusion, following the second or third COVID-19 mRNA vaccine dose, QuantiFERON SARS-CoV-2 detected positive responses in a certain percentage of the vaccinees, possibly because of waning immunity, reduced assay sensitivity, or lack of T-cell response induction in some vaccinees. The detection of positive responses was higher when the Starter + Extended Pack was used. PROSPERO Registration Number: CRD42023431315.