COVID-19: Rapid antigen detection for SARS-CoV-2 by lateral flow assay: A national systematic evaluation of sensitivity and specificity for mass-testing

Abstract

Background Lateral flow device (LFD) viral antigen immunoassays have been developed around the world as diagnostic tests for SARS-CoV-2 infection. They have been proposed to deliver an infrastructure-light, cost-economical solution giving results within half an hour. Methods LFDs were initially reviewed by a Department of Health and Social Care team, part of the UK government, from which 64 were selected for further evaluation from 1st August to 15th December 2020. Standardised laboratory evaluations, and for those that met the published criteria, field testing in the Falcon-C19 research study and UK pilots were performed (UK COVID-19 testing centres, hospital, schools, armed forces). Findings 4/64 LFDs so far have desirable performance characteristics (orient Gene, Deepblue, Abbott and Innova SARS-CoV-2 Antigen Rapid Qualitative Test). All these LFDs have a viral antigen detection of >90% at 100,000 RNA copies/ml. 8951 Innova LFD tests were performed with a kit failure rate of 5.6% (502/8951, 95% CI: 5.1–6.1), false positive rate of 0.32% (22/6954, 95% CI: 0.20–0.48). Viral antigen detection/sensitivity across the sampling cohort when performed by laboratory scientists was 78.8% (156/198, 95% CI 72.4–84.3). Interpretation Our results suggest LFDs have promising performance characteristics for mass population testing and can be used to identify infectious positive individuals. The Innova LFD shows good viral antigen detection/sensitivity with excellent specificity, although kit failure rates and the impact of training are potential issues. These results support the expanded evaluation of LFDs, and assessment of greater access to testing on COVID-19 transmission. Funding Department of Health and Social Care. University of Oxford. Public Health England Porton Down, Manchester University NHS Foundation Trust, National Institute of Health Research.

Comparative Study of In Situ Techniques to Enlarge Gold Nanoparticles for Highly Sensitive Lateral Flow Immunoassay of SARS-CoV-2

“…Such rapid and easy-to-use tests are in demand by public health [40]. LFIA antigen tests have already shown promising performance for mass population screening [41]. The expected further developments in the area of point-of-care detection of SARS-CoV-2 will be related to highly sensitive and multiplex assays.…”

Gold–Oligonucleotide Nanoconstructs Engineered to Detect Conserved Enteroviral Nucleic Acid Sequences

“…This is because traditional instruments and methods are often uneconomical, require extensive training to correctly operate, and are time-consuming, such that they do not meet the requirements of a typical doctor-patient consultation (~10 min) [17]. Microtiter-based ELISA has demonstrated breakthroughs in the field through the detection of viruses [18] and has been advanced for clinical settings through the development of lateral flow assays [19], which prove to be economical, simple, and rapid [20,21]. Excellent examples of cases in which ELISA-based lateral flow assays are widely implemented include the ubiquitous pregnancy test [22] and more recently SARS-CoV-2 [23].…”

Letter to the Editor regarding Peto T; UK COVID-19 Lateral Flow Oversight Team: COVID-19: Rapid antigen detection for SARS-CoV-2 by lateral flow assay

“…The FDA have raised concerns on the evidence for the Innova LFT [2]. Peto report key studies from Porton Down and the University of Oxford which form the evidence base for use of Innova and its rebranded version (the NHS Test-and-Trace LFT) [3]. We highly commend the authors for kindly sharing their data [4] with our Cochrane team for inclusion in our systematic review of the accuracy of rapid antigen tests [5].…”

“…1) The paper computes specificity by combining data on 6954 Innova tests across studies from "negative samples" (Table 2) [3]. This implies all 6954 samples were verified by a reference standard which returned a negative result (anticipated to be RT-PCR, but no reference standard is described).…”

“…This important result is not reported in the publication or preprint. (The publication suggests 16 false positives and higher total numbers tested [3], so the exact value may slightly differ). The positive predictive value of school testing has been an important debate [7], particularly given school testing was originally introduced without RT-PCR confirmatory testing, thus its omission from this report is of relevance.…”