Abstract
We investigated feasibility and accuracy of an interferon-γ release assay (IGRA) for detection of T-cell responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Whole ...blood IGRA accurately distinguished between convalescent and uninfected healthy blood donors with a predominantly CD4+ T-cell response. SARS-CoV-2 IGRA may serve as a useful diagnostic tool in managing the coronavirus disease 2019 pandemic.
•The QuantiFERON SARS-CoV-2 research use only assay response is mediated by CD4+ and CD8+ T cells.•Immune response to the antigen (Ag)2 tube is more accurate than that to the Ag1 tube.•Responses to ...QuantiFERON SARS-CoV-2 tubes are lower compared with a homemade test.•The QuantiFERON SARS-CoV-2 difference in accuracy is likely because of the peptide composition.
Objectives: In this study, we aimed to characterize the SARS-CoV-2-specific T cell response detected by the QuantiFERON SARS-CoV-2 research use only assay in terms of accuracy and T cell subsets involved compared with a homemade interferon (IFN)-γ release assay (IGRA).
Methods: We evaluated T cell response by the standardized QuantiFERON SARS-CoV-2 tubes (antigen Ag1 and Ag2) and a homemade IGRA quantifying IFN-γ response to SARS-CoV-2 spike peptides (homemade-IGRA-SPIKE test). We evaluated the T cell subsets mediating the specific response using flow cytometry.
Results: We prospectively enrolled 66 individuals: COVID-19 or post-COVID-19 subjects and NO-COVID-19-vaccinated subjects, including healthy donors and immunocompromised subjects. The standardized kit detected 62.1% (41/66) of T cell responders. Ag2 tube showed a higher IFN-γ quantitative and qualitative response. Ag1 tube response was mainly mediated by CD4+ T cells; Ag2 tube response was mediated by CD4+ and CD8+ T cells. The homemade-IGRA-SPIKE test detected a higher number of responders (52/66, 78.8%) than the QuantiFERON SARS-CoV-2 assay (P = 0.056). The response was found in both T cell subsets, although a higher magnitude and response rate was observed in the CD4+ T cell subset.
Conclusion: The QuantiFERON SARS-CoV-2 response is mediated by CD4+ and CD8+ T cells. A lower number of responders is found compared with the homemade-IGRA-SPIKE test, likely because of the different peptide composition.
An estimated one fourth of the world's population is infected with Mycobacterium tuberculosis, and 5–10% of those infected develop tuberculosis in their lifetime. Preventing tuberculosis is one of ...the most underutilized but essential components of curtailing the tuberculosis epidemic. Moreover, current evidence illustrates that tuberculosis manifestations occur along a dynamic spectrum from infection to disease rather than a binary state as historically conceptualized. Elucidating determinants of transition between these states is crucial to decreasing the tuberculosis burden and reaching the END-TB Strategy goals as defined by the WHO. Vaccination, detection of infection, and provision of preventive treatment are key elements of tuberculosis prevention.
This review provides a comprehensive summary of recent evidence and state-of-the-art updates on advancements to prevent tuberculosis in various settings and high-risk populations.
We identified relevant studies in the literature and synthesized the findings to provide an overview of the current state of tuberculosis prevention strategies and latest research developments.
We present the current knowledge and recommendations regarding tuberculosis prevention, with a focus on M. bovis Bacille-Calmette-Guérin vaccination and novel vaccine candidates, tests for latent infection with M. tuberculosis, regimens available for tuberculosis preventive treatment and recommendations in low- and high-burden settings.
Effective tuberculosis prevention worldwide requires a multipronged approach that addresses social determinants, and improves access to tuberculosis detection and to new short tuberculosis preventive treatment regimens. Robust collaboration and innovative research are needed to reduce the global burden of tuberculosis and develop new detection tools, vaccines, and preventive treatments that serve all populations and ages.
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QuantiFERON-TB Gold Plus (QFT-Plus) is a new-generation QuantiFERON-TB Gold In-Tube (QFT-GIT) assay which has two antigen-coated tubes called TB1, which contains long peptides derived from ESAT-6 and ...CFP-10, and TB2, which contains the same components as TB1 and additional short peptides which potentially stimulate CD8
T cells through the presentation of major histocompatibility complex class I. This is the first study to compare QFT-Plus and QFT-GIT for use in the diagnosis of latent tuberculosis infection (LTBI) among immunocompromised patients in the Republic of Korea. Among 317 consecutive patients who underwent screening for LTBI before solid organ or hematopoietic stem cell transplantation and tumor necrosis factor alpha inhibitor treatment, LTBI was identified in 92 (29.0%) and 88 (27.8%) patients by QFT-GIT and QFT-Plus, respectively. The rate of concordance between QFT-GIT and QFT-Plus was 93.7% (κ value, 0.860), and the indeterminate rate (3.2%) was similar between QFT-GIT and QFT-Plus. Of 20 (6.3%) samples with discordant results, 11 (55.0%) and 7 (35.0%) were positive by QFT-GIT alone and QFT-Plus alone, respectively, and 2 (15.0%) were indeterminate by each assay. The interferon gamma level in samples with discordant results ranged from 0.39 to 1.10 IU/ml, except for one sample, in which the gamma interferon level was 2.97 IU/ml only in TB2. Conclusively, there was a high degree of agreement between the results of QFT-GIT and QFT-Plus for the screening of immunocompromised patients for LTBI. The reactivity in TB2 contributed substantially to the difference between QFT-GIT and QFT-Plus, particularly in solid organ transplant candidates. The significance of the discrete responses in TB1 and TB2 of QFT-Plus needs to be explored further by means of an immunological and clinical approach in different patient groups and clinical settings.
Latent tuberculosis infection (LTBI) is a subclinical mycobacterial infection defined on the basis of cellular immune response to mycobacterial antigens. The tuberculin skin test (TST) and the ...interferon gamma release assay (IGRA) are currently used to establish the diagnosis of LTB. However, neither TST nor IGRA is useful to discriminate between active and latent tuberculosis. Moreover, these tests cannot be used to predict whether an individual with LTBI will develop active tuberculosis (TB) or whether therapy for LTBI could be effective to decrease the risk of developing active TB. Therefore, in this article, we review current approaches and some efforts to identify an immunological marker that could be useful in distinguishing LTBI from TB and in evaluating the effectiveness of treatment of LTB on the risk of progression to active TB.
•Baricitinib has been suggested as a promising therapy for COVID-19.•Baricitinib modulates in vitro SARS-CoV-2-specific-response in a whole blood platform.•Baricitinib decreases ...viral-specific-response mainly in mild/moderate COVID-19.
Baricitinib seems a promising therapy for COVID-19. To fully-investigate its effects, we in-vitro evaluated the impact of baricitinib on the SARS-CoV-2-specific-response using the whole-blood platform.
We evaluated baricitinib effect on the IFN-γ-release and on a panel of soluble factors by multiplex-technology after stimulating whole-blood from 39 COVID-19 patients with SARS-CoV-2 antigens. Staphylococcal Enterotoxin B (SEB) antigen was used as a positive control.
In-vitro exogenous addition of baricitinib significantly decreased IFN-γ response to spike- (median: 0.21, IQR: 0.01–1; spike+baricitinib 1000 nM median: 0.05, IQR: 0–0.18; p < 0.0001) and to the remainder-antigens (median: 0.08 IQR: 0–0.55; remainder-antigens+baricitinib 1000 nM median: 0.03, IQR: 0–0.14; p = 0.0013). Moreover, baricitinib significantly decreased SEB-induced response (median: 12.52, IQR: 9.7–15.2; SEB+baricitinib 1000 nM median: 8, IQR: 1.44–12.16; p < 0.0001). Baricitinib did modulate other soluble factors besides IFN-γ, significantly decreasing the spike-specific-response mediated by IL-17, IL-1β, IL-6, TNF-α, IL-4, IL-13, IL-1ra, IL-10, GM-CSF, FGF, IP-10, MCP-1, MIP-1β (p ≤ 0.0156). The baricitinib-decreased SARS-CoV-2-specific-response was observed mainly in mild/moderate COVID-19 and in those with lymphocyte count ≥1 × 103/µl.
Exogenous addition of baricitinib decreases the in-vitro SARS-CoV-2-specific response in COVID-19 patients using a whole-blood platform. These results are the first to show the effects of this therapy on the immune-specific viral response.
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Le diagnostic de tuberculose oculaire (TO) demeure difficile et la contribution du QuantiFERON® (QFT) reste à préciser malgré sa généralisation en France. L’objectif de cette étude est d’évaluer dans ...quelles situations d’inflammation oculaire (IO) le QFT doit être prescrit et l’intérêt du nouveau test QuantiFERON®-TB-Plus (QFT-Plus) dans la TO.
Étude monocentrique, observationnelle, effectuée en ophtalmologie sur une période de 5 mois. Les critères d’inclusion étaient l’existence d’une IO avec QFT-Plus demandé à visée étiologique. Sur 316 dossiers consécutifs, 72 ont été exclus (tests indéterminés, bilan préthérapeutique, données manquantes et mauvaise indication) et 244 retenus et répartis en deux groupes : groupe 1 (uvéite antérieure/épislérite, n=129), groupe 2 (uvéite intermédiaire/postérieure/névrite optique/myosite oculaire, n=115). Tous les patients QFT+ ont bénéficié d’un bilan étiologique avec imagerie thoracique.
Quarante-cinq patients, d’âge médian de 52±12 ans, avaient un QFT+ (18,5 %), incluant 18 patients dans le groupe 1 et 27 dans le groupe 2. Un voyage en pays d’endémie et un contage tuberculeux et des anomalies de l’imagerie thoracique étaient identifiés, respectivement dans 70 %, 27 % et 22 % des cas. L’IO était chronique chez 36 % des patients (groupe 1, n=4/18 ; groupe 2, n=12/27). Aucun des 18 patients du groupe 1, n’a reçu de quadrithérapie antituberculeuse, ni n’a présenté de rechute à 1 an de suivi. Un diagnostic alterne était retrouvé chez 15 % des patients du groupe 2. Parmi les 23 patients, sans étiologie identifiée, 13 (59 %) avaient au moins un élément sémiologique ophtalmologique prédictif de TO (synéchies postérieures, vascularite rétinienne, granulomes choroïdiens). Onze patients ont bénéficié d’un traitement antituberculeux (TAT) d’épreuve (rifampicine/isoniazide/pirilène/éthambutol) de six mois. La présence de granulomes à l’angiographie et d’anomalies radiologiques à l’imagerie thoracique était statistiquement plus fréquente parmi les patients ayant reçu un TAT (respectivement, p=0,001 et 0,03). Une guérison à 12 mois était observée pour 8 patients (73 %), considéré a posteriori comme TO. Neuf patients ont reçu trois mois de bithérapie (rifampicine/isoniazide) sans que l’on puisse déterminer l’impact sur l’IO. La comparaison des réponses lymphocytaires T entre la stimulation CD4 par peptides ESAT-6/CFP-10 ou la co-stimulation CD4/CD8 était similaire, ne retrouvant que 4 discordances sur 244 tests (1,5 %). Aucun de ces 4 patients n'avait de TO.
La fréquence de positivité du QFT est élevée parmi les patients consultant pour une IO postérieure. Les anomalies radiologiques et la présence de granulomes semblent être les éléments qui ont incités le clinicien à initier un TAT aux patients QFT+, avec guérison dans 73 % des cas. Le QFT-Plus ne semble pas plus pertinent que le QFT-TB-Gold dans l’exploration d’une IO. Des études prospectives restent nécessaires pour codifier l’utilisation du QFT dans le bilan étiologique des IO et définir les indications du TAT d’épreuve et de ses modalités.
Ocular tuberculosis (TB) diagnosisremains difficult and quantiferon (QFT) contribution needs still yet to be specified, despite its generalization in France. The purpose of this observational study is to assess in which ocular inflammation (OI) presentation QFT is prescribed and to evaluate the added value of new QuantiFERON®-TB Gold Plus (QFT-Plus) test for diagnosis ocular TB diagnosis.
Monocentric, observational study, carried out in an ophthalmology department over a period of 5 months. Inclusion criteria were defined as an existence of an OI for which a QFT-Plus test was part of the etiological investigations. Of the 316 consecutive files, 72 were excluded (indeterminate test, prescription before anti-TNFα or immunosuppressant initiation, missing data, wrong indication) and 244 were selected and divided into two groups: group one (anterior uveitis/episcleritis, n=129) and group two (intermediate/posterior uveitis/optic neuritis/ocular myositis, n=115). All positive QFT patients underwent an etiological investigation including thoracic imaging.
Forty-five patients, aged 52±12 years, had positive QFT (18.5%), including 18 patients for group 1 and 27 for group 2. Living in TB-endemic area, TB exposure and chest imaging abnormalities were identified in 70%, 27% and 22% of cases, respectively. OI was chronic in 36% of cases (group one, 4/18; group two, 12/27). None of the 18 patients, in group 1, received anti-tuberculosis treatment (ATT) or experienced a relapse during one-year follow-up. Four QFT+ patients, from group 2 (15%) had another associated disease explaining their uveitis. Among the 23 other patients without identified etiology, 13 had at least one relevant ophthalmological signs predictive of TB uveitis (posterior synechiae, retinal vasculitis and/or choroidal granuloma) (59%). Eleven patients received a 6-month ATT trial. Radiological abnormalities and granulomas at angiography were significantly more frequent among treated patients (p=0.03 and 0.001, respectively). A full OI recovery was observed for 8 patients (73%), considered ex-post as ocular TB. Nine patients in group 2 received rifampicin/isoniazid dual therapy for 3 months, but no conclusion could be drawn as to the benefit of such prescription on OI. QFT rate comparison, according to CD4 stimulation by ESAT-6/CFP-10 peptides or by CD4/CD8 co-stimulation, was comparable and found only 4 cases of discrepancy (1.6%). None of these 4 cases had ocular TB diagnosis.
Positive QFT frequency among patients consulting for posterior OI remains high. In this study, radiological abnormalities and granulomas at angiography seemed to be more closely related to clinician decision for starting ATT trial in QFT+ patients, which was effective in 73% of cases. QFT-Plus does not seem more relevant than QFT-TB in exploring an OI. Prospective studies are necessary to codify QFT management in the etiological assessment of OI and clearly define ATT trial indications as well as their modalities.
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