Self-testing is an effective tool to bridge the testing gap for several infectious diseases; however, its performance in detecting SARS-CoV-2 using antigen-detection rapid diagnostic tests (Ag-RDTs) has not been systematically reviewed. This study aimed to inform WHO guidelines by evaluating the accuracy of COVID-19 self-testing and self-sampling coupled with professional Ag-RDT conduct and interpretation. Articles on this topic were searched until November 7th, 2022. Concordance between self-testing/self-sampling and fully professional-use Ag-RDTs was assessed using Cohen’s kappa. Bivariate meta-analysis yielded pooled performance estimates. Quality and certainty of evidence were evaluated using QUADAS-2 and GRADE tools. Among 43 studies included, twelve reported on self-testing, and 31 assessed self-sampling only. Around 49.6% showed low risk of bias. Overall concordance with professional-use Ag-RDTs was high (kappa 0.91 [95% confidence interval (CI) 0.88–0.94]). Comparing self-testing/self-sampling to molecular testing, the pooled sensitivity and specificity were 70.5% (95% CI 64.3–76.0) and 99.4% (95% CI 99.1–99.6), respectively. Higher sensitivity (i.e., 93.6% [95% CI 90.4–96.8] for Ct < 25) was estimated in subgroups with higher viral loads using Ct values as a proxy. Despite high heterogeneity among studies, COVID-19 self-testing/self-sampling exhibits high concordance with professional-use Ag-RDTs. This suggests that self-testing/self-sampling can be offered as part of COVID-19 testing strategies.Trial registration: PROSPERO: CRD42021250706.

The COVID-19 pandemic brought diagnostics into the spotlight in an unprecedented way not only for case management but also for population health, surveillance, and monitoring. The industry saw notable levels of investment and accelerated research which sparked a wave of innovation. Simple non-invasive sampling methods such as nasal swabs have become widely used in settings ranging from tertiary hospitals to the community. Self-testing has also been adopted as standard practice using not only conventional lateral flow tests but novel and affordable point-of-care molecular diagnostics. The use of new technologies, including artificial intelligence-based diagnostics, have rapidly expanded in the clinical setting. The capacity for next-generation sequencing and acceptance of digital health has significantly increased. However, 4 years after the pandemic started, the market for SARS-CoV-2 tests is saturated, and developers may benefit from leveraging their innovations for other diseases; tuberculosis (TB) is a worthwhile portfolio expansion for diagnostics developers given the extremely high disease burden, supportive environment from not-for-profit initiatives and governments, and the urgent need to overcome the long-standing dearth of innovation in the TB diagnostics field. In exchange, the current challenges in TB detection may be resolved by adopting enhanced swab-based molecular methods, instrument-based, higher sensitivity antigen detection technologies, and/or artificial intelligence-based digital health technologies developed for COVID-19. The aim of this article is to review how such innovative approaches for COVID-19 diagnosis can be applied to TB to have a comparable impact.

Rationale: C-reactive protein (CRP)-based tuberculosis (TB) screening is recommended for people with HIV. However, its performance among people without HIV and in diverse settings is unknown. Objectives: In a multicountry study, we aimed to determine whether CRP meets the minimum accuracy targets (sensitivity ⩾ 90%, specificity ⩾ 70%) for an effective TB screening test. Methods: Consecutive outpatient adults with cough ⩾2 weeks from five TB endemic countries in Africa and Asia had baseline blood collected for point-of-care CRP testing and HIV and diabetes screening. Sputum samples were collected for Xpert MTB/RIF Ultra (Xpert) testing and culture. CRP sensitivity and specificity (5 mg/L cut-point) was determined in reference to sputum test results and compared by country, sex, and HIV and diabetes status. Variables affecting CRP performance were identified using a multivariate receiver operating curve regression model. Measurements and Main Results: Among 2,904 participants, of whom 613 (21%) had microbiologically confirmed TB, CRP sensitivity was 84% (95% confidence interval [CI], 81–87%) and specificity was 61% (95% CI, 59–63%). CRP accuracy varied geographically, with higher sensitivity in African countries (⩾91%) than Asian countries (64–82%). Sensitivity was higher among men than women (86% vs. 78%; difference, +8%; 95% CI, 1–15%) and specificity was lower among people with HIV than people without HIV (64% vs. 45%; difference, +19%; 95% CI, 13–25%). Receiver operating curve regression identified country and measures of TB disease severity as predictors of CRP performance. Conclusions: Overall, CRP did not achieve the minimum accuracy targets, and its performance varied by setting and in some subgroups, likely reflecting population differences in mycobacterial load.

Improved diagnostic tools for tuberculosis that are suitable for use in peripheral health centers are essential for reducing the persistent gap between estimated and notified cases. The diagnostic accuracy and usability of the MiniDock MTB test for detecting pulmonary tuberculosis is unknown. We conducted a prospective, cross-sectional study at outpatient centers in India, Nigeria, the Philippines, South Africa, Uganda, Vietnam, and Zambia. Patients 12 years of age or older with presumptive pulmonary tuberculosis were enrolled between September 12, 2024, and March 31, 2025. Assessment with MiniDock MTB was performed with sputum swabs and tongue swabs. Diagnostic accuracy was evaluated against a sputum-culture-based reference and as compared with sputum-smear microscopy and Xpert MTB/RIF Ultra assay. Usability was assessed with a system usability scale and direct observation. A total of 1380 participants were enrolled; 255 (18.5%) had human immunodeficiency virus infection and 226 (16.4%) had culture-confirmed tuberculosis. MiniDock MTB sensitivity was 85.7% (95% confidence interval [CI], 80.4 to 90.0) with sputum and 79.6% (95% CI, 73.8 to 84.7) with tongue swabs; specificity was greater than 97.5% for both. Results of sputum tests with MiniDock MTB closely matched those with Xpert MTB/RIF Ultra for sensitivity (difference, -2.8 percentage points; 95% CI, -6.0 to 0.5). MiniDock MTB had greater sensitivity than smear microscopy for tests of sputum (difference, 24.3 percentage points; 95% CI, 17.9 to 30.7) and tongue swabs (difference, 18.3 percentage points; 95% CI, 12.0 to 24.7). The test showed diagnostic accuracy that was consistent with World Health Organization (WHO) accuracy targets for near-point-of-care tuberculosis diagnostics (≥85% sensitivity for sputum and ≥75% for nonsputum and ≥98% specificity for both). The median score on the system usability scale (range, 0 to 100, with higher scores indicating better perceived usability) was 75 (interquartile range, 65 to 80), which indicated good usability. No adverse events related to the index test were reported. MiniDock MTB met WHO targets for diagnostic accuracy and usability for tuberculosis detection across diverse clinical settings. (Funded by the National Institutes of Health and others; Rapid Research in Diagnostics Development for TB Network and Assessing Diagnostics at Point-of-Care for Tuberculosis ClinicalTrials.gov numbers, NCT04923958 and NCT05941052.).

Background: During the COVID-19 pandemic, antigen diagnostic tests were frequently used for screening, triage, and diagnosis. Novel instrument-based antigen tests (iAg tests) hold the promise of outperforming their instrument-free, visually-read counterparts. Here, we provide a systematic review and meta-analysis of the SARS-CoV-2 iAg tests’ clinical accuracy. Methods: We systematically searched MEDLINE (via PubMed), Web of Science, medRxiv, and bioRxiv for articles published before November 7th, 2022, evaluating the accuracy of iAg tests for SARS-CoV-2 detection. We performed a random effects meta-analysis to estimate sensitivity and specificity and used the QUADAS-2 tool to assess study quality and risk of bias. Sub-group analysis was conducted based on Ct value range, IFU-conformity, age, symptom presence and duration, and the variant of concern. Results: We screened the titles and abstracts of 20,431 articles and included 114 publications that fulfilled the inclusion criteria. Additionally, we incorporated three articles sourced from the FIND website, totaling 117 studies encompassing 95,181 individuals, which evaluated the clinical accuracy of 24 commercial COVID-19 iAg tests. The studies varied in risk of bias but showed high applicability. Of 24 iAg tests from 99 studies assessed in the meta-analysis, the pooled sensitivity and specificity compared to molecular testing of a paired NP swab sample were 76.7% (95% CI 73.5 to 79.7) and 98.4% (95% CI 98.0 to 98.7), respectively. Higher sensitivity was noted in individuals with high viral load (99.6% [95% CI 96.8 to 100] at Ct-level ≤ 20) and within the first week of symptom onset (84.6% [95% CI 78.2 to 89.3]), but did not differ between tests conducted as per manufacturer’s instructions and those conducted differently, or between point-of-care and lab-based testing. Conclusion: Overall, iAg tests have a high pooled specificity but a moderate pooled sensitivity, according to our analysis. The pooled sensitivity increases with lower Ct-values (a proxy for viral load), or within the first week of symptom onset, enabling reliable identification of most COVID-19 cases and highlighting the importance of context in test selection. The study underscores the need for careful evaluation considering performance variations and operational features of iAg tests.

Introduction In 2014, the WHO published high-priority target product profiles (TPPs) for new tuberculosis (TB) diagnostics to align end-user needs with test targets and specifications; nevertheless, no TB test meets these targets to date. The COVID-19-driven momentum in the diagnostics world offers an opportunity to address the long-standing lack of innovation in the field of TB diagnostics. This scoping review aims to summarise point-of-care (POC) molecular and antigen tests for COVID-19 diagnosis that, when applied to TB, potentially meet WHO TPPs. This summary of currently available innovative diagnostic tools will guide the development of novel TB diagnostics toward the WHO-set targets. Methods and analysis We will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension Scoping Reviews recommendations. MEDLINE (via PubMed), bioRxiv, MedRxiv and other publicly available in vitro diagnostic test databases were searched on 23 November 2022. POC antigen or molecular tests developed for SARS-CoV-2 detection that meet the eligibility criteria will be included in the review. Developer description, test description, operation characteristics, pricing information, performance and commercialisation status of diagnostic tests identified will be extracted using a predefined standardised data extraction form. Two reviewers will independently perform the screening and data extraction. A narrative synthesis of the final data will be provided. Ethics and dissemination No ethical approval is required because individual patient data will not be included. The findings will be published in open-access scientific journals.