Concurrent Tuberculosis and COVID-19 Testing from a Single Sputum Specimen for Enhanced Disease Detection

Abstract

Background/Objectives: Tuberculosis (TB) and SARS-CoV-2 share similar symptoms and transmission routes. In early 2021, USAID and Stop TB Partnership recommended an integrated approach for simultaneous COVID-19 and TB testing in high TB burden countries for individuals with respiratory symptoms. In this evaluation, we tested a single sputum for both SARS-CoV-2 and Mycobacterium tuberculosis complex (MTBC) from participants at two healthcare facilities in South Africa. The diagnostic accuracy of the Xpert Xpress SARS-CoV-2 (Xpress) assay using a sputum swab capture method was assessed by comparing the results with routine SARS-CoV-2 testing, while also determining the prevalence of TB and TB-COVID-19 co-infection in the study population. Methods: A total of 2274 individuals were screened for enrolment. Eligibility included the presence of respiratory symptoms, close contact with a person with TB, TB diagnosis in the last two years or a person living with HIV. Sputum from 1032 participants was tested on the Xpress assay using a swab capture method while residual sputum was tested on the Xpert MTB/RIF Ultra assay for MTBC and rifampicin-resistance detection. Concordance between the Xpress assay and routine SARS-CoV-2 testing was assessed. Results: The Xpress assay detected SARS-CoV-2 in 183/1032 (18%) participants, TB was detected in 35/1032 (3%) participants and 10/1032 (1%) participants were co-infected with TB and COVID-19. The Xpress assay showed substantial agreement with routine testing (Kappa: 0.755). Conclusions: The study findings underscore a substantial identification of TB and rifampicin-resistant TB that would have been missed if bi-disease testing was not performed. In addition, the sputum swab capture method demonstrated reliable performance for SARS-CoV-2 detection.

Keywords: COVID-19; Mycobacterium tuberculosis; SARS-CoV-2; bi-disease testing; tuberculosis.

Figure 1

Description of participant recruitment, specimen testing and data descriptions for statistical analysis. HIV, human immunodeficiency virus; MTBC, Mycobacterium tuberculosis complex; NP, nasopharyngeal swab; PCR, polymerase chain reaction. Xpert Xpress SARS-CoV-2 was used to detect SARS-CoV-2 on sputum swabs, while Xpert MTB/RIF Ultra was used to detect MTBC and rifampicin resistance-associated mutations in sputum. Routine SARS-CoV-2 testing was performed on nasopharyngeal swabs. ¹ Inconclusive result determined using National Health Laboratory Services algorithm.

Figure 2

Venn diagram illustrating the number of participants who tested positive for Mycobacterium tuberculosis complex (MTBC) and/or SARS-CoV-2 using Xpert MTB/RIF Ultra, Xpert Xpress SARS-CoV-2 and routine SARS-CoV-2 PCR testing. Xpert Xpress SARS-CoV-2 was used to detect SARS-CoV-2 on sputum swabs, while Xpert MTB/RIF Ultra was used to detect MTBC and rifampicin resistance-associated mutations in sputum. Routine SARS-CoV-2 testing was performed on nasopharyngeal swabs. The numbers represent the distribution of positive results among the three testing methods. The overlapping areas indicate participants with concordant results across multiple methods.