Evaluation of QuantiFERON SARS-CoV-2 interferon-γ release assay following SARS-CoV-2 infection and vaccination

• Published in: Clinical and experimental immunology Vol. 212; no. 3; pp. 249 - 261
• Main Authors: Johnson, Síle A, Phillips, Eloise, Adele, Sandra, Longet, Stephanie, Malone, Tom, Mason, Chris, Stafford, Lizzie, Jamsen, Anni, Gardiner, Siobhan, Deeks, Alexandra, Neo, Janice, Blurton, Emily J, White, Jemima, Ali, Muhammed, Kronsteiner, Barbara, Wilson, Joseph D, Skelly, Dónal T, Jeffery, Katie, Conlon, Christopher P, Goulder, Philip, Consortium, PITCH, Carroll, Miles, Barnes, Eleanor, Klenerman, Paul, Dunachie, Susanna J
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 05.06.2023
• Subjects: Antibodies, Viral; COVID-19; Cross-Sectional Studies; Humans; Infection/Infectious Disease; Interferon-gamma Release Tests; SARS-CoV-2; Vaccination; COVID-19; SARS-CoV-2; QuantiFERON; T cells; ELISpot
• ISSN: 0009-9104; 1365-2249; 1365-2249
• DOI: 10.1093/cei/uxad027

Abstract T cells are important in preventing severe disease from SARS-CoV-2, but scalable and field-adaptable alternatives to expert T-cell assays are needed. The interferon-gamma release assay QuantiFERON platform was developed to detect T-cell responses to SARS-CoV-2 from whole blood with relatively basic equipment and flexibility of processing timelines. Forty-eight participants with different infection and vaccination backgrounds were recruited. Whole blood samples were analysed using the QuantiFERON SARS-CoV-2 assay in parallel with the well-established ‘Protective Immunity from T Cells in Healthcare workers’ (PITCH) ELISpot, which can evaluate spike-specific T-cell responses. The primary aims of this cross-sectional observational cohort study were to establish if the QuantiFERON SARS-Co-V-2 assay could discern differences between specified groups and to assess the sensitivity of the assay compared with the PITCH ELISpot. The QuantiFERON SARS-CoV-2 distinguished acutely infected individuals (12–21 days post positive PCR) from naïve individuals (P < 0.0001) with 100% sensitivity and specificity for SARS-CoV-2 T cells, whilst the PITCH ELISpot had reduced sensitivity (62.5%) for the acute infection group. Sensitivity with QuantiFERON for previous infection was 12.5% (172–444 days post positive test) and was inferior to the PITCH ELISpot (75%). Although the QuantiFERON assay could discern differences between unvaccinated and vaccinated individuals (55–166 days since second vaccination), the latter also had reduced sensitivity (44.4%) compared to the PITCH ELISpot (66.6%). The QuantiFERON SARS-CoV-2 assay showed potential as a T- cell evaluation tool soon after SARS-CoV-2 infection but has lower sensitivity for use in reliable evaluation of vaccination or more distant infection. With the exception of acute infection group, the PITCH ELISpot S1 + S2 had greater sensitivity for SARS-CoV-2 specific T-cell responses compared with the QuantiFERON SARS-CoV-2 assay tube Ag3. Graphical Abstract Graphical Abstract