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

10.1101/2022.09.03.22279558

MedRxiv

Contributing to research themes:

This research has not been peer-reviewed. It is a preliminary report that should not be regarded as conclusive, guide clinical practice or health-related behaviour, or be reported in news media as established information.

Background:

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.

Methods:

48 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.

Aims:

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 to the PITCH ELISpot.

Findings:

The QuantiFERON SARS-CoV-2 distinguished acutely infected individuals (12-21 days post positive PCR) from naive 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 (55.5%) compared to the PITCH ELISpot (66.6%).

Conclusion:

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.

Author list:

Affiliations:

  1. Peter Medawar Building for Pathogen Research, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK
  2. University of Oxford Medical School, University of Oxford, Oxford, UK
  3. University Hospital of Derby and Burton, UK
  4. Centre For Global Health Research, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK
  5. Mahidol-Oxford Tropical Medicine Research Unit, Mahidol University, Bangkok, Thailand
  6. Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK
  7. Pandemic Sciences Institute, Nuffield Department of Medicine, University of Oxford, UK
  8. Oxford University Hospitals NHS Foundation Trust, Oxford, UK
  9. Department of Experimental Medicine, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK
  10. Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK 
  11. Radcliffe Department of Medicine, University of Oxford, Oxford, UK
  12. Peter Medawar Building for Pathogen Research, Department of Paediatrics, University of Oxford, Oxford, UK
  13. NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, UK
  14. Translational Gastroenterology Unit, University of Oxford, Oxford, UK

Authors:

Síle A Johnson1,2,3, Eloise Phillips1, Sandra Adele1,4,5, Stephanie Longet6,7, Tom Malone1, Chris Mason2, Lizzie Stafford8,9, Anni Jamsen8,9, Siobhan Gardiner8,9, Alexandra Deeks1,9, Janice Neo3, Emily J Blurton3, Jemima White2, Muhammed Ali1,4,5, Barbara Kronsteiner-Dobramysl1,4, Dónal T Skelly1,8,10, Katie Jeffery8,11, Christopher P Conlon4,8, Philip Goulder12, PITCH Consortium, Miles Carroll6,7, Eleanor Barnes1,8,13,14, Paul Klenerman1,8,13,14, Susanna J Dunachie1,4,5,8