One test for TB and COVID-19 shows mixed results

The COVID-19 pandemic disrupted tuberculosis case detection and management, and overlapping symptoms and risk factors can make it hard to tell the two diseases apart. To address this problem, a team led by corresponding author Adam Penn-Nicholson ran a prospective multicentre diagnostic accuracy study to see how well a single molecular test could look for both illnesses at once. The test under evaluation was the Truenat MTB Ultima/COVID-19 assay, designed to run on a combined sputum plus nasopharyngeal swab specimen in a single multiplex molecular assay. Researchers enrolled consenting adults with presumptive tuberculosis by convenience sampling at sites in Uganda, Peru, South Africa, and India between August 2022 and December 2023 (ClinicalTrials.gov NCT05405296). The goal was to measure sensitivity, specificity and operational characteristics of the Truenat assay compared with established laboratory standards, and to explore whether one rapid test could help clinicians facing patients with overlapping respiratory symptoms.

The study used a microbiological reference standard of sputum GeneXpert MTB/RIF Ultra and culture for tuberculosis, and national RT-PCR for COVID-19. Wilson’s score method was used to calculate sensitivity and specificity. A total of 1,928 participants were enrolled; median age was 38 years (IQR 28-50), 359/1928 (18.6%) had previously had TB, and 287/1928 (14.9%) were HIV-positive. Overall prevalence of tuberculosis in the study was 24.8% (95% CI 22.9-26.8%). COVID-19 prevalence was 3.8% (3.1-4.8%) overall and 4.7% (3.1-7.0%) among those with confirmed tuberculosis. For tuberculosis detection, the Truenat MTB Ultima/COVID-19 assay had an overall sensitivity of 79.8% (95% CI 76.0-83.2%) and specificity of 98.9% (98.2-99.3%). In paired sample comparisons against sputum TB culture, the Truenat assay showed a 9.5% (6.5-13.1%) decreased sensitivity compared to GeneXpert MTB/RIF Ultra (82.8% [78.9-86.1%] vs 92.4% [89.4-94.5%]). For COVID-19, the Truenat assay sensitivity was 64.4% (52.9-74.4%) with specificity of 99.2% (98.7-99.5%).

The results show a mixed picture: the Truenat MTB Ultima/COVID-19 assay was very specific for both tuberculosis and COVID-19, meaning positive results are likely to be true positives, but sensitivity was only moderate for tuberculosis and lower for COVID-19, so a negative result would not reliably rule out either disease. The study therefore did not demonstrate optimal diagnostic performance for this combined test. At the same time, the work highlights an important direction for diagnostics: rapid, integrated tests that can detect tuberculosis alongside other respiratory infections could be valuable where symptoms and risk factors overlap and where the COVID-19 pandemic has disrupted tuberculosis services. The authors note the potential and the need for rapid development of such integrated tools, while the performance numbers in this study underline that improvements in sensitivity will be needed before a single multiplex test like Truenat MTB Ultima/COVID-19 can replace or stand alone against current standards such as GeneXpert MTB/RIF Ultra and culture for tuberculosis or national RT-PCR for COVID-19.