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
Plasmodium, the unicellular parasite that causes malaria, evolved a highly unusual mode of reproduction. During its complex life cycle, invasive or transmissive stages alternate with proliferating stages, where a single parasite can produce tens of thousands of progeny. In the clinically relevant blood stage of infection, the parasite replicates its genome up to thirty times and forms a multinucleated cell before daughter cells are assembled. Thus, within a single cell cycle, Plasmodium develops from a haploid to a polypoid cell, harboring multiple copies of its genome. Polyploidy creates several biological challenges, such as imbalances in genome output, and cells can respond to this by changing their size and/or alter the production of RNA species and protein to achieve expression homeostasis. However, the effects and possible adaptations of Plasmodium to the massively increasing DNA content are unknown. Here, we revisit and embed current Plasmodium literature in the context of polyploidy and propose potential mechanisms of the parasite to cope with the increasing gene dosage.
Our manufacturer-independent, prospective diagnostic accuracy study assessed clinical performance in participants presumed to have a SARS-CoV-2 infection at three study sites in two countries. We assessed the accuracy overall and in predefined subgroups (
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values and symptom duration).
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