AUTHOR=Jacquier Marine , Binquet Christine , Manoha Catherine , Audia Sylvain , Simonet-Lamm Anne-Laure , Casenaz Alice , Sow Amadou-Khalilou , Piroth Lionel , Blot Mathieu TITLE=Beyond QuantiFERON-TB Results, the Added Value of a Weak Mitogen Response JOURNAL=Frontiers in Medicine VOLUME=Volume 9 - 2022 YEAR=2022 URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2022.876864 DOI=10.3389/fmed.2022.876864 ISSN=2296-858X ABSTRACT=Introduction: While QuantiFERON-TB (QFT) is frequently used, little attention is paid to the mitogen response. How it could be impacted and associated with outcomes is poorly known. Methods: Retrospective, case-control study in hospitalized patients who underwent QFT testing in two hospitals between 2016 and 2019. We defined two groups of cases with either negative (interferon (IFN)-γ ≤0.5 IU/ml, official threshold) or weak (0.5-2 IU/ml) mitogen response, and one group of controls with normal (>2 IU/ml) mitogen response. Results: 872 patients were included. An ongoing infection was independently associated with both a negative (RR=4.34; 95% CI=2.94-6.41) and a weak mitogen response (RR=2.44; 95% CI=1.66-3.58). Among tuberculosis patients, a weak mitogen response was associated with a false-negative QFT result (75%) compared to a normal response (20%). Decreasing mitogen response (normal, weak and negative, respectively) was associated with increasing length of hospital stay (median (interquartile range) 5 (3-13), 11 (5-21) and 15 (10-30) days; p<0.001) and increasing hospital mortality (3%, 7% and 15%; p<0.001). Conclusion: Clinicians should take notice of the mitogen response since IFN-γ concentrations lower than <2 IU/ml were associated with false-negative QFT results in tuberculosis patients, independently associated with ongoing infections, and could be associated with worse prognosis.