ABSTRACT
The Centers for Disease Control allows rapid antigen testing (RAT) towards the end of a 5-day isolation for COVID-19 infection to determine eligibility to leave isolation. The impact of a test-to-return (TTR) program in schools is unknown. In January 2022 a Massachusetts school district initiated a TTR program utilizing a single school-administered RAT on days 5-9 after symptom onset or positive test, whichever was first. Of 636 students with COVID-19 infection, 408 (64.2%) participated in TTR; of these, 128 (31.4%) had a positive TTR rapid antigen test. Students who were symptomatic at any time during their infection were more likely to have a positive TTR than those who were never symptomatic (43.1% vs. 17.3%); positivity rates were lower when TTR was performed later during days 6-9. TTR may identify students who carry higher viral loads after recovery from COVID-19 infection thereby extending their isolation, while facilitating earlier return of those with negative results.
ABSTRACT
BackgroundSARS-CoV-2 antigen rapid diagnostic tests (Ag-RDTs) are increasingly being integrated in testing strategies around the world. Studies of the Ag-RDTs have shown variable performance. In this systematic review and meta-analysis, we assessed the clinical accuracy (sensitivity and specificity) of commercially available Ag-RDTs. Methods and ResultsWe registered the review on PROSPERO (Registration number: CRD42020225140). We systematically searched multiple databases (PubMed, Web of Science Core Collection, medRvix and bioRvix, FIND) for publications evaluating the accuracy of Ag-RDTs for SARS-CoV-2 up until April 30th, 2021. Descriptive analyses of all studies were performed and when more than four studies were available, a random-effects meta-analysis was used to estimate pooled sensitivity and specificity in comparison to reverse transcriptase polymerase chain reaction testing. We assessed heterogeneity by subgroup analyses, and rated study quality and risk of bias using the QUADAS 2 assessment tool. From a total of 14,254 articles, we included 133 analytical and clinical studies resulting in 214 clinical accuracy data sets with 112,323 samples. Across all meta-analyzed samples, the pooled Ag-RDT sensitivity was 71.2% (95% confidence interval [CI] 68.2 to 74.0) and increased to 76.3% (CI 73.1 to 79.2) if analysis was restricted to studies that followed the Ag-RDT manufacturers instructions. The LumiraDx showed the highest sensitivity with 88.2% (CI 59.0 to 97.5). Of instrument-free Ag-RDTs, Standard Q nasal performed best with 80.2% sensitivity (CI 70.3 to 87.4). Across all Ag-RDTs sensitivity was markedly better on samples with lower Ct-values, i.e., <20 (96.5%, CI 92.6 to 98.4) and <25 (95.8%, CI 92.3 to 97.8), in comparison to those with Ct [≥]25 (50.7%, CI 35.6 to 65.8) and [≥]30 (20.9%, CI 12.5 to 32.8). Testing in the first week from symptom onset resulted in substantially higher sensitivity (83.8%, CI 76.3 to 89.2) compared to testing after one week (61.5%, CI 52.2 to 70.0). The best Ag-RDT sensitivity was found with anterior nasal sampling (75.5%, CI 70.4 to 79.9) in comparison to other sample types (e.g., nasopharyngeal 71.6%, CI 68.1 to 74.9) although CIs were overlapping. Concerns of bias were raised across all data sets, and financial support from the manufacturer was reported in 24.1% of data sets. Our analysis was limited by the included studies heterogeneity in design and reporting, making it difficult to draw conclusions from. ConclusionIn this study we found that Ag-RDTs detect the vast majority of cases within the first week of symptom onset and those with high viral load. Thus, they can have high utility for diagnostic purposes in the early phase of disease, making them a valuable tool to fight the spread of SARS-CoV-2. Standardization in conduct and reporting of clinical accuracy studies would improve comparability and use of data. AUTHOR SUMMARYWhy was this study done? - Antigen rapid diagnostic tests (Ag-RDTs) are considered an important diagnostic tool to fight the spread of SARS-CoV-2 - An increasing number of Ag-RDTs is offered on the market, and a constantly growing body of literature evaluating their performance is available - To inform decision makers about the best test to choose, an up to date summary of their performance is needed What did the researchers do and find? - On a weekly basis, we search multiple data bases for evaluations of Ag-RDTs detecting SARS-CoV-2 and post the results on www.diagnosticsglobalhealth.org - Based on the search results up until April 30th, 2021, we conducted a systematic review and meta-analysis, including a total of 133 clinical and analytical accuracy studies - Across all meta-analyzed studies, when Ag-RDTs were performed according to manufacturers recommendations, they showed a sensitivity of 76.3% (CI 73.1 to 79.2), with the LumiraDx (sensitivity 88.2%, CI 59.0 to 97.5) and of the instrument-free Ag-RDT Standard Q (74.9% sensitivity, CI 69.3 to 79.7) performing best. - Across all Ag-RDTs, sensitivity increased to 95.8% (CI 92.3 to 97.8) when restricting the analysis to samples with high viral loads (i.e., a Ct-value <25) and to 83.8% (CI 76.3 to 89.2) when tests were performed on patients within the first week after symptom onset What do these findings mean? - Ag-RDTs detect the vast majority of cases within the first week of symptom onset and those with high viral load. Thus, they can have high utility for diagnostic purposes in the early phase of disease - Out of all assessed tests, the Lumira Dx showed the highest accuracy. The Standard Q wasthe best performing test when only considering those that dont require an instrument - A standardization of reporting methods for clinical accuracy studies would enhance future test-comparisons
ABSTRACT
BackgroundReliable point-of-care (POC) diagnostics not requiring laboratory infrastructure could be a game changer in the COVID-19 pandemic, particularly in the Global South. We assessed performance, limit of detection and ease-of-use of three antigen-detecting, rapid POC tests (Ag-RDT) for SARS-CoV-2. MethodsThis prospective, multi-centre diagnostic accuracy study recruited participants suspected to have SARS-CoV-2 in Germany and the UK. Paired nasopharyngeal swabs (NP) or NP and/or oropharyngeal swabs (OP) were collected from participants (one for clinical RT-PCR and one for Ag-RDT). Performance of each of three Ag-RDTs was compared to RT-PCR overall, and according to predefined subcategories e.g. cycle threshold (CT)-value, days from symptoms onset, etc. In addition, limited verification of the analytical limit-of-detection (LOD) was determined. To understand the usability a System Usability Scale (SUS) questionnaire and ease-of-use (EoU) assessment were performed. ResultsBetween April 17th and August 25th, 2020, 2417 participants were enrolled, with 70 (3.0%) testing positive by RT-PCR. The best-performing test (SD Biosensor, Inc. STANDARD Q) was 76x6% (95% Confidence Interval (CI) 62x8-86x4) sensitive and 99x3% (CI 98x6-99x6) specific. A sub-analysis showed all samples with RT-PCR CT-values <25 were detectable by STANDARD Q. The test was considered easy-to-use (SUS 86/100) and suitable for POC. Bioeasy and Coris showed specificity of 93x1% (CI 91x0%-94x8%) and 95x8% (CI 93x4%-97x4%), respectively, not meeting the predefined target of [≥]98%. ConclusionThere is large variability in performance of Ag-RDT with SD Biosensor showing promise. Given the usability at POC, this test is likely to have impact despite imperfect sensitivity; however further research and modelling are needed.