Clinical performance evaluation of SARS-CoV-2 rapid antigen testing in point of care usage in comparison to RT-qPCR

Wagenhäuser, Isabell; Knies, Kerstin; Rauschenberger, Vera; Eisenmann, Michael; McDonogh, Miriam; Petri, Nils; Andrés, Oliver; Flemming, Sven; Gawlik, Micha; Papsdorf, Michael; Taurines, Regina; Böhm, Hartmut; Förster, Johannes; Weismann, Dirk; Weißbrich, Benedikt; Dölken, Lars; Liese, Johannes G.; Kurzai, Oliver; Vogel, Ulrich; Krone, Manuel

doi:10.1016/j.ebiom.2021.103455

Cited by 70 publications

(69 citation statements)

References 25 publications

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“…At the end of the data extraction process, 37 studies were still in preprint form [4,171,173,174,177,180,190,192,201,204,205,207,211,[214][215][216]218,220,222,223,225,227,231,233,234,238,240,244,247,253,257,265,267,284,287,290,293]. All studies were written in English, except for 2 in Spanish [175,280].…”

Section: Summary Of Studiesmentioning

confidence: 99%

Accuracy of novel antigen rapid diagnostics for SARS-CoV-2: A living systematic review and meta-analysis

et al. 2021

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Background SARS-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 findings We registered the review on PROSPERO (registration number: CRD42020225140). We systematically searched multiple databases (PubMed, Web of Science Core Collection, medRvix, bioRvix, and FIND) for publications evaluating the accuracy of Ag-RDTs for SARS-CoV-2 up until 30 April 2021. Descriptive analyses of all studies were performed, and when more than 4 studies were available, a random-effects meta-analysis was used to estimate pooled sensitivity and specificity in comparison to reverse transcription polymerase chain reaction (RT-PCR) 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 datasets with 112,323 samples. Across all meta-analyzed samples, the pooled Ag-RDT sensitivity and specificity were 71.2% (95% CI 68.2% to 74.0%) and 98.9% (95% CI 98.6% to 99.1%), respectively. Sensitivity increased to 76.3% (95% CI 73.1% to 79.2%) if analysis was restricted to studies that followed the Ag-RDT manufacturers’ instructions. LumiraDx showed the highest sensitivity, with 88.2% (95% CI 59.0% to 97.5%). Of instrument-free Ag-RDTs, Standard Q nasal performed best, with 80.2% sensitivity (95% CI 70.3% to 87.4%). Across all Ag-RDTs, sensitivity was markedly better on samples with lower RT-PCR cycle threshold (Ct) values, i.e., <20 (96.5%, 95% CI 92.6% to 98.4%) and <25 (95.8%, 95% CI 92.3% to 97.8%), in comparison to those with Ct ≥ 25 (50.7%, 95% CI 35.6% to 65.8%) and ≥30 (20.9%, 95% CI 12.5% to 32.8%). Testing in the first week from symptom onset resulted in substantially higher sensitivity (83.8%, 95% CI 76.3% to 89.2%) compared to testing after 1 week (61.5%, 95% CI 52.2% to 70.0%). The best Ag-RDT sensitivity was found with anterior nasal sampling (75.5%, 95% CI 70.4% to 79.9%), in comparison to other sample types (e.g., nasopharyngeal, 71.6%, 95% CI 68.1% to 74.9%), although CIs were overlapping. Concerns of bias were raised across all datasets, and financial support from the manufacturer was reported in 24.1% of datasets. Our analysis was limited by the included studies’ heterogeneity in design and reporting. Conclusions In this study we found that Ag-RDTs detect the vast majority of SARS-CoV-2-infected persons 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.

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Section: Summary Of Studiesmentioning

confidence: 99%

Accuracy of novel antigen rapid diagnostics for SARS-CoV-2: A living systematic review and meta-analysis

et al. 2021

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Section: Discussionmentioning

confidence: 99%

“…The majority of tests investigated in this study reliably detected the Ct25 test sample as SARS-CoV-2 positive (Group II). Some of these AgPOCTs have been thoroughly characterized, including Abbott, RapiGEN, Healgen, nal von minden and SD Biosensor by Corman and colleagues (Corman et al, 2021) among others (Strömer et al, 2021;Stokes et al, 2021;Merino et al, 2021;Schildgen et al, 2021;Seynaeve et al, 2021;Nordgren et al;Puyskens et al, 2021;Scheiblauer et al, 2021;Kohmer et al, 2021;Wagenhäuser et al, 2021;Berger et al, 2021;Jegerlehner et al, 2021;Iglòi et al, 2021;Bekliz et al, 2021;Cubas-Atienzar et al, 2021, Haage et al, and more). Corman and colleagues determined 95% limits of detection for each AgPOCT using 138 SARS-CoV-2 positive clinical samples with viral loads ranging from 1.9*10⁴ to 1.8*10⁹ genome copies per ml.…”

Section: Discussionmentioning

confidence: 99%

Rapid comparative evaluation of SARS-CoV-2 rapid point-of-care antigen tests

Denzler

Jacobs

Witte

et al. 2021

Preprint

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Background: Currently, more than 500 different AgPOCTs for SARS-CoV-2 diagnostics are on sale, for many of which no data about sensitivity other than self-acclaimed values by the manufacturers are available. In many cases these do not reflect real-life diagnostic sensitivities. Therefore, manufacturer-independent quality checks of available AgPOCTs are needed, given the potential implications of false-negative results. Objective: The objective of this study was to develop a scalable approach for direct comparison of the analytical sensitivities of commercially available SARS-CoV-2 antigen point-of-care tests (AgPOCTs) in order to rapidly identify poor performing products. Methods: We present a methodology for quick assessment of the sensitivity of SARS-CoV-2 lateral flow test stripes suitable for quality evaluation of many different products. We established reference samples with high, medium and low SARS-CoV-2 viral loads along with a SARS-CoV-2 negative control sample. Test samples were used to semi-quantitatively assess the analytical sensitivities of 32 different commercial AgPOCTs in a head-to-head comparison. Results: Among 32 SARS-CoV-2 AgPOCTs tested, we observe sensitivity differences across a broad range of viral loads (~7.0*10⁸ to ~1.7*10⁵ SARS-CoV-2 genome copies per ml). 23 AgPOCTs detected the Ct25 test sample (~1.4*10⁶ copies/ ml), while only five tests detected the Ct28 test sample (~1.7*10⁵ copies/ ml). In the low range of analytical sensitivity we found three saliva spit tests only delivering positive results for the Ct21 sample (~2.2*10⁷ copies/ ml). Comparison with published data support our AgPOCT ranking. Importantly, we identified an AgPOCT offered in many local drugstores and supermarkets, which did not reliably recognize the sample with highest viral load (Ct16 test sample with ~7.0*10⁸ copies/ ml) leading to serious doubts in its usefulness in SARS-CoV-2 diagnostics. Conclusion: The rapid sensitivity assessment procedure presented here provides useful estimations on the analytical sensitivities of 32 AgPOCTs and identified a widely-spread AgPOCT with concerningly low sensitivity.

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“…Wagenh€ auser and colleagues [5] reported RDT sensitivity at the lower end of that observed in other recent large-scale studies of RDT testing strategies which also included large proportions of asymptomatic people [8,9], so what are the possible explanations? Between-assay variations in sensitivity and the use of possibly less sensitive oropharyngeal samples may well have contributed [10], however the low prevalence of SARS-CoV-2 and differences in the case-mix of participants, particularly in terms of the distribution of viral loads are likely to be a driving factor.…”

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confidence: 91%

“…In this article of EBioMedicine [5], Isabell Wagenh€ auser and colleagues provide a significant contribution to the evidence base for targeted community-based screening with RDTs. The 'community' consisted of over 5000 participants at a tertiary care hospital facility including all admitted patients or those accompanying patients, and hospital employees with respiratory symptoms or close contact with confirmed cases.…”

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confidence: 99%

COVID-19 rapid antigen testing strategies require careful evaluation

Dinnes¹

2021

EBioMedicine

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Clinical performance evaluation of SARS-CoV-2 rapid antigen testing in point of care usage in comparison to RT-qPCR

Cited by 70 publications

References 25 publications

Accuracy of novel antigen rapid diagnostics for SARS-CoV-2: A living systematic review and meta-analysis

Accuracy of novel antigen rapid diagnostics for SARS-CoV-2: A living systematic review and meta-analysis

Rapid comparative evaluation of SARS-CoV-2 rapid point-of-care antigen tests

COVID-19 rapid antigen testing strategies require careful evaluation

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