Evaluation of accuracy, exclusivity, limit-of-detection and ease-of-use of LumiraDxâ„¢: An antigen-detecting point-of-care device for SARS-CoV-2

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

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 SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s15010-021-01681-y.