Evaluation of accuracy, exclusivity, limit-of-detection and ease-of-use of LumiraDx™: An antigen-detecting point-of-care device for SARS-CoV-2
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Abstract
Purpose
Rapid antigen-detecting tests (Ag-RDTs) for severe acute respiratory syndrome coronavirus 2 ( SARS-CoV-2 ) can transform pandemic control. Thus far, sensitivity (≤ 85%) of lateral-flow assays has limited scale-up. Conceivably, microfluidic immunofluorescence Ag-RDTs could increase sensitivity for SARS-CoV-2 detection.
Methods
This multi-centre diagnostic accuracy study investigated performance of the microfluidic immunofluorescence LumiraDx™ assay, enrolling symptomatic and asymptomatic participants with suspected SARS-CoV-2 infection. Participants collected a supervised nasal mid-turbinate (NMT) self-swab for Ag-RDT testing, in addition to a professionally collected nasopharyngeal (NP) swab for routine testing with reverse transcriptase polymerase chain reaction (RT-PCR). Results were compared to calculate sensitivity and specificity. Sub-analyses investigated the results by viral load, symptom presence and duration. An analytical study assessed exclusivity and limit-of-detection (LOD). In addition, we evaluated ease-of-use.
Results
The study was conducted between November 2nd 2020 and 4th of December 2020. 761 participants were enrolled, with 486 participants reporting symptoms on testing day. 120 out of 146 RT-PCR positive cases were detected positive by LumiraDx™, resulting in a sensitivity of 82.2% (95% CI 75.2–87.5%). Specificity was 99.3% (CI 98.3–99.7%). Sensitivity was increased in individuals with viral load ≥ 7 log10 SARS-CoV2 RNA copies/ml (93.8%; CI 86.2–97.3%). Testing against common respiratory commensals and pathogens showed no cross-reactivity and LOD was estimated to be 2–56 PFU/mL. The ease-of-use-assessment was favourable for lower throughput settings.
Conclusion
The LumiraDx™ assay showed excellent analytical sensitivity, exclusivity and clinical specificity with good clinical sensitivity using supervised NMT self-sampling.
Trial registration number and registration date
DRKS00021220 and 01.04.2020
Article activity feed
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SciScore for 10.1101/2021.03.02.21252430: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization not detected. Blinding Laboratory personal for Ag-RDT testing was blinded to the results of RT-PCR testing and vice versa. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
No key resources detected.
Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:Nevertheless, it is to note, that the RT-PCR reference standard also has its limitations, as it is not always a meaningful test when …
SciScore for 10.1101/2021.03.02.21252430: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization not detected. Blinding Laboratory personal for Ag-RDT testing was blinded to the results of RT-PCR testing and vice versa. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
No key resources detected.
Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:Nevertheless, it is to note, that the RT-PCR reference standard also has its limitations, as it is not always a meaningful test when considering viable virus and risk of transmission (21). This is also demonstrated by a recent study of an Ag-RDT in the USA, where the sensitivity was 92.6% in symptomatic individuals when compared to viral culture versus 64.2% when compared to RT-PCR (22). Thus, using the RT-PCR reference standard, we might have underestimated the performance of the Ag-RDT when it comes to detection of viable virus. We also acknowledge that the Lumira assay is only recommended for symptomatic patients. Sensitivity was slightly higher among symptomatic patients (82.5%, 95% CI:75.3%-87.9%) as compared to asymptomatic individuals (77.8%, 45.3%-93.7%), with overlapping confidence intervals. This was to be expected from the lower viral load observed in the limited number of asymptomatic positive cases. As cohort studies have shown the viral load kinetics between asymptomatic and symptomatic infections to be similar, the findings of the lower viral load and thus lower sensitivity observed in our study is most likely attributable to chance or to capturing asymptomatic patients too early (maybe also prior to symptom development). Further need for studies remain to better understand the performance in asymptomatic patients (23). The excellent clinical specificity of the LumiraDx™ was confirmed by the analytical exclusivity testing. Our findings indicate no cross-reactiv...
Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
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