Evaluation of accuracy, exclusivity, limit-of-detection and ease-of-use of LumiraDx™-Antigen-detecting point-of-care device for <i>SARS-CoV-2</i>

Krüger, Lisa J.; Klein, Jürgen; Tobian, Frank; Gaeddert, Mary; Lainati, Federica; Klemm, Sarah; Schnitzler, Paul; Bartenschlager, Ralf; Cerikan, Berati; Neufeldt, Christopher J; Nikolai, Olga; Lindner, Andreas; Mockenhaupt, Frank P.; Seybold, Joachim; Jones, Terry C.; Corman, Victor M.; Mockenhaupt, Frank P.; Knorr, Britta; Welker, Andreas; Vos, Margaretha de; Sacks, Jilian A.; Denkinger, Claudia M.

doi:10.1101/2021.03.02.21252430

Cited by 19 publications

(11 citation statements)

References 21 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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“…At the end of the data extraction process, 37 studies were still in preprint form [4,171,173,174,177,180,190,192,201,204,205,207,211,214–216,218,220,222,223,225,227,231,233,234,238,240,244,247,253,257,265,267,284,287,290,293]. All studies were written in English, except for two in Spanish [175, 280].…”

Section: Resultsmentioning

confidence: 99%

The accuracy of novel antigen rapid diagnostics for SARS-CoV-2: a living systematic review and meta-analysis

Brümmer

Katzenschlager

Gaeddert

et al. 2021

Preprint

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Background: SARS-CoV-2 antigen rapid diagnostic tests (Ag-RDTs) are increasingly being inte-grated 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 (sensi-tivity and specificity) of commercially available Ag-RDTs. Methods: We registered the review on PROSPERO (Registration number: CRD42020225140). We systematically searched multiple databases (PubMed, Web of Science Core Collection, medRvix and bioRvix, FINDdx) for publications up until December 11th, 2020. Descriptive analyses of all studies were performed and when more than four studies were avail-able, 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 ((1) performed conform with manufacturers instructions for use (IFU) or not, (2) symptomatic vs. asymptomatic, (3) duration of symptoms less than seven days vs. more than seven days, (4) Ct-value <25 vs. <30 vs. >30, (5) by sample type)) and with meta-regression. We assessed study quality and risk of bias using the QUADAS 2 assessment tool. Results: From a total of 11,715 articles, we extracted 98 analytical and clinical data sets. 74 clinical accuracy data sets were evaluated that included 31,202 samples. Across all meta-analyzed samples, the pooled Ag-RDT sensitivity was 73.8% (CI 68.6 to 78.5). If analysis was re-stricted to studies that followed the Ag-RDT manufacturers instructions using fresh upper res-piratory swab samples, the sensitivity increased to 79.1% (95%CI 75.0 to 82.8). The SD Biosensor Standard Q and Abbott Panbio showed the highest sensitivity with 81.7% and 72.7%, respectively. The best Ag-RDT performance was found with nasopharyngeal sampling (77.3%, CI 72.0 to 81.9) in comparison to other sample types (e.g., anterior nasal or mid turbinate 63.5%, CI 49.5 to 75.5). Testing in the first week from symptom onset resulted in higher sensitivity (87.5%, CI 86.0 to 89.1) compared to testing after one week (64.1%, CI 54.4 to 73.8). The tests performed markedly better on samples with lower Ct-values, i.e., <30 (87.9%, CI 86.7 to 88.8), in comparison to those with Ct >30 (47.8%, CI 41.1 to 54.5). Bias concerns were raised across all data sets, and financial support from the manufacturer was reported in 28.2% of data sets. Conclusion: As Ag-RDTs detect most cases within the first week of symptom onset and those with high viral load, they can have high utility for screening purposes in the early phase of disease, and thus can be a valuable tool to fight the spread of SARS-CoV-2. Standardization of con-duct and reporting of clinical accuracy studies would improve comparability and use of data.

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“…We estimated that our test sample collection covers a range from ~7.0*10⁸ (Ct=16) to ~1.7*10⁵ (Ct=28) SARS-CoV-2 genome copies per ml (Supplemental Table S4). We qualitatively validated our test sample collection using the LumiraDx SARS-CoV-2 Ag Test device, which was shown to have a high analytical sensitivity (Krüger et al, 2021). We used 50 µl of test sample for the LumiraDx analysis as well as for all…”

Section: Generation Of Test Samples For Standardized Agpoct Evaluationmentioning

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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Evaluation of accuracy, exclusivity, limit-of-detection and ease-of-use of LumiraDx™-Antigen-detecting point-of-care device for SARS-CoV-2

Cited by 19 publications

References 21 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

The 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

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