Low agreement and frequent invalid controls in two SARS-CoV-2 T-cell assays in people with compromised immune function

Annette Audigé; Alain Amstutz; Macé M Schuurmans; Patrizia Amico; Dominique L Braun; Marcel P Stoeckle; Barbara Hasse; René Hage; Dominik Damm; Michael Tamm; Nicolas J Mueller; Huldrych F Günthard; Michael T Koller; Christof M Schönenberger; Alexandra Griessbach; Niklaus D Labhardt; Roger D Kouyos; Alexandra Trkola; Michael Huber; Katharina Kusejko; Heiner C Bucher; Irene A Abela; Matthias Briel; Frédérique Chammartin; Benjamin Speich; Swiss HIV Cohort Study, and the Swiss Transplant Cohort Study

doi:10.1371/journal.pone.0317965

Low agreement and frequent invalid controls in two SARS-CoV-2 T-cell assays in people with compromised immune function

PLoS One. 2025 Jan 24;20(1):e0317965. doi: 10.1371/journal.pone.0317965. eCollection 2025.

Authors

Annette Audigé¹, Alain Amstutz^{2

3

4}, Macé M Schuurmans⁵, Patrizia Amico⁶, Dominique L Braun^{1

7}, Marcel P Stoeckle⁸, Barbara Hasse⁷, René Hage⁵, Dominik Damm⁵, Michael Tamm⁹, Nicolas J Mueller⁷, Huldrych F Günthard^{1

7}, Michael T Koller^{6

10}, Christof M Schönenberger², Alexandra Griessbach², Niklaus D Labhardt², Roger D Kouyos^{1

7}, Alexandra Trkola¹, Michael Huber¹, Katharina Kusejko^{1

7}, Heiner C Bucher², Irene A Abela^{1

7}, Matthias Briel^{2

11}, Frédérique Chammartin², Benjamin Speich²; Swiss HIV Cohort Study, and the Swiss Transplant Cohort Study

Affiliations

¹ Institute of Medical Virology, University of Zurich, Zurich, Switzerland.
² Division of Clinical Epidemiology, Department of Clinical Research, University Hospital Basel, University of Basel, Basel, Switzerland.
³ Oslo Center for Biostatistics and Epidemiology (OCBE), Oslo University Hospital, University of Oslo, Oslo, Norway.
⁴ Bristol Medical School, University of Bristol, Bristol, United Kingdom.
⁵ Division of Pulmonology, University Hospital Zurich, Zurich, Switzerland.
⁶ Clinic for Transplantation Immunology and Nephrology, University Hospital Basel, Basel, Switzerland.
⁷ Department of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland.
⁸ Division of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, University of Basel, Basel, Switzerland.
⁹ Clinic of Respiratory Medicine and Pulmonary Cell Research, University Hospital Basel, Basel, Switzerland.
¹⁰ Swiss Transplant Cohort Study, University Hospital Basel, Basel, Switzerland.
¹¹ Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Canada.

Abstract

T-cell response plays an important role in SARS-CoV-2 immunogenicity. For people living with HIV (PWH) and solid organ transplant (SOT) recipients there is limited evidence on the reliability of commercially available T-cell tests. We assessed 173 blood samples from 81 participants (62 samples from 35 PWH; 111 samples from 46 SOT recipients [lung and kidney]) with two commercial SARS-CoV-2 Interferon-γ (IFN-γ) release assays (IGRA; SARS-CoV-2 IGRA by Euroimmun, and IGRA SARS-CoV-2 by Roche). The reliability between the tests was judged as low (Cohen's kappa [κ] = 0.20; overall percent agreement [OPA] = 66%). A high proportion of tests were invalid (22% Euroimmun; 8% Roche). When excluding these invalid tests, the agreement was higher (κ = 0.43; OPA = 90%). The low reliability between the two T-cell tests indicates that results should be interpreted with caution in SOT recipients and PWH and that SARS-CoV-2 T-cell tests need to be optimized and further validated for use in vulnerable patient populations.

Copyright: © 2025 Audigé et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

MeSH terms

Adult
Aged
COVID-19* / diagnosis
COVID-19* / immunology
COVID-19* / virology
Female
HIV Infections / immunology
Humans
Immunocompromised Host*
Interferon-gamma
Interferon-gamma Release Tests* / methods
Male
Middle Aged
Reproducibility of Results
SARS-CoV-2* / immunology
T-Lymphocytes* / immunology

Substances

Interferon-gamma

Grants and funding

The vaccine study in which the samples for the T-cell assays were collected (i.e. COVERALL-3) was funded by Moderna. Roche provided all reagents for the T-cell assay Elecsys® IGRA SARS-CoV-2. The set-up of the study platform (i.e. COVERALL) was funded by the Swiss National Science Foundation (grant # 31CA30_196245). The Swiss HIV Cohort Study (SHCS) and the Swiss Transplant Cohort Study (STCS) are funded by the Swiss National Science Foundation (SHCS: grant #177499 and #201369, STCS: grant #33CS30_177522). Alain Amstutz received his salary for the duration of this project from the Junior Research Fund of the University of Basel. Christof Manuel Schönenberger received his salary for the duration of this project from the Swiss National Science Foundation (grant # 323530_221860) and the Janggen Pöhn Foundation. The funders had no role in data collection, analysis, and preparation of the manuscript. Before submission, Moderna and Roche had the right to read the manuscript and make suggestions, but the study team was not obliged to accept suggestions and the Funders were not involved in the final decision to submit to the journal.