Performance of the T-SPOTⓇ.COVID test for detecting SARS-CoV-2-responsive T cells.

OBJECTIVE: To evaluate the performance of the T-SPOT.COVID test for identifying SARS-CoV-2-responsive T-cells in participants with SARS-CoV-2 infection. METHODS: The T-SPOT.COVID test uses ELISpot interferon-gamma release assay (IGRA) methodology to measure T cell responses to SARS-CoV-2 spike S1 and nucleocapsid peptides. T-SPOT.COVID and anti-N immunoglobulin (Ig) G serology tests were performed on blood from 186 patients with nucleic acid amplification test (NAAT)-confirmed-SARS-CoV-2 infection and 100 control group participants. RESULTS: In the 2-8 weeks after NAAT-diagnosed SARS-CoV-2 infection, the T-SPOT.COVID test detected 98.4% (63 of 64) of infected participants, while anti-N IgG serology detected 82.8%. In the first 2 weeks after diagnosis, during adaptive immune response activation, there were less reactive T-SPOT.COVID responses (75.7%, 28 of 37 infected participants) and many less seropositive responses (32.4%). Response numbers tapered after 8 weeks; however, T-SPOT.COVID test continued to detect most participants with confirmed infection (83.6%, 56 of 67) and continued to out-perform serology (52.2%). T-SPOT.COVID response due to cross-reactive T cells was ruled out by demonstrating that, of 44 control group participants with T cells responsive to 4 human common cold coronavirus peptides, only 1 was T-SPOT.COVID reactive. CONCLUSION: The T-SPOT.COVID test performed well in detecting SARS-CoV-2-sensitized T-cells over many months.

T-SPOT.TB Interferon-γ Release Assay Performance in Healthcare Worker Screening at Nineteen U.S. Hospitals.

RATIONALE: Interferon-γ release assays have significant advantages over tuberculin skin testing in many clinical situations. However, recent studies have called into question their reliability in serial testing of healthcare workers because of reportedly high rates of positivity and high conversion/reversion rates on retesting. OBJECTIVES: To define the performance characteristics of the T-SPOT.TB test, an interferon-γ release assay, during serial screening programs of healthcare workers at 19 U.S. hospitals. METHODS: A total of 42,155 T-SPOT.TB test results from healthcare workers at 19 geographically diverse hospitals obtained for routine tuberculosis screening programs were analyzed to determine the rates of positivity, reversion, and conversion in serial testing data. MEASUREMENTS AND MAIN RESULTS: In 19,630 evaluable serial pairs from 16,076 healthcare workers, the mean test positivity rate was 2.3% (range, 0.0-27.4%). The mean conversion rate was 0.8% (range, 0.0-2.5%), and the mean reversion rate was 17.6%. Positivity and conversion rates correlated with known tuberculosis risk factors including age and sex. The observed specificity of the T-SPOT.TB test was at least 98.6%. CONCLUSIONS: The high concordance and test completion rates in this study suggest that the T-SPOT.TB test is a reliable tool for healthcare worker serial screening. As expected, the observed positivity rates were lower compared with the tuberculin skin test, likely reflecting the higher specificity of this test. Furthermore, the observed rates of conversion were low and significantly correlated with the geographic incidence of tuberculosis. Our findings suggest that the T-SPOT.TB test is an accurate and reliable way to screen healthcare workers.

Screening health care workers with interferon-γ release assay versus tuberculin skin test: impact on costs and adherence to testing (the SWITCH study).

OBJECTIVE: To determine the price point at which an interferon-γ release assay (IGRA) is less costly than a tuberculin skin test (TST) for health care employee tuberculosis screening. METHODS: A multidecision tree-based cost model incorporating inputs gathered from time-motion studies and parallel testing by IGRA and TST was conducted in a subset of our employees. RESULTS: Administering a TST testing program costs $73.20 per person screened, $90.80 per new hire, and $63.42 per annual screen. Use of an IGRA for employee health testing is cost saving at an IGRA test cost of $54.83 or less per test and resulted in higher completion rates because of the elimination of the need for a second visit to interpret the TST. CONCLUSIONS: Using an IGRA for employee health screening can be an institutional cost saving and results in higher compliance rates.

Diagnosis of tuberculosis infection in patients awaiting liver transplantation.

This study examined the performance of a tuberculosis (TB)-specific enzyme-linked immunospot assay in 48 patients awaiting liver transplantation. They were tested with T-SPOT.TB, tuberculin skin test (TST), and lymphocyte transformation test (LTT) using tuberculin as a stimulus. A questionnaire was used to gain information on TB exposure. Four patients were defined as positive by T-SPOT.TB, 6 by TST, and 28 by LTT. The patients displaying positive results to T-SPOT.TB were also positive in the TST and LTT. We considered them to have latent TB because they were repeatedly (two or three times) positive to the T-SPOT.TB and reported TB exposure. Active TB was excluded by negative multislice computed tomography, negative culture, and absence of symptoms. In 1 patient, T-cell reactivity toward TB peptides was lost 1 and 2 months posttransplantation. Another patient, however, tested 8 and 13 months posttransplantation, displayed measurable cellular TB immune responses. This finding suggests that the measurement of cellular TB immune responses shortly after transplantation may fail. If possible, patients with end-stage liver disease should be screened for TB prior to transplantation. Our data are the first evidence that T-SPOT.TB may be useful to diagnose latent TB in patients awaiting liver transplantation.

Intradermal ballistic delivery of micro-particles into excised human skin for pharmaceutical applications.

A unique form of needle-free drug and vaccine delivery is under investigation. The principle of the concept is to accelerate pharmaceuticals in particle form to a momentum sufficient to penetrate the outer layer of the human skin for a pharmacological effect. The relationship between the key particle impact parameters and particle penetration depth in excised human skin has been experimentally determined. Research devices have been used to deliver particles of a range of radii (0.89-53 microm), and density (1.08-18.2 g/cm3) at controlled and incremental impact velocities between 160 and 640 m/s. Analysis of the particle impact data reveals particle penetration depth as a function of particle density, radius and impact velocity. The experimental relationship provides a criterion for the optimal selection of particle parameters and velocity to target specific layers within the skin. Furthermore, some sources of variability in penetration depth have also been established. The experimental data have also been compared with a mechanistic Unified Penetration Model with good agreement.