A systematic review and meta-analysis was 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-off³0.15IU/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 Program Tool. A meta-analysis was conducted using a Random-Effects model. Heterogeneity and publication bias were assessed. Eleven eligible studies (with 5-75 vaccinated immunocompetent participants) were identified. For COVID-19-naive participants, £3 months after the second dose, the pooled PR (Random-Effects model) was 81 [95% Confidence Interval (95%CI):71-92]%. Comparing the Starter vs. the Starter+Extended Pack, a significant difference in PRs was detected (79.3% vs. 92.2%, p-value=0.039). At 3-6 and >6 months after the second dose and at ³3 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, ³6 months after the third dose, the pooled PR was 81(95%CI:67-92)%. In conclusion, following the second or third COVID-19 mRNA vaccine, QuantiFERON-SARS-CoV-2 detected positive responses in a certain percentage of the vaccinees. This detection was higher when the Starter+Extended Pack was used. Possible explanations for the assay’s negative results in a subset of the participants could be: waning immunity, reduced sensitivity compared to other T-cell assays or lack of T-cell response induction in some vaccinees.
(PROSPERO Registration Number:CRD42023431315)