Nicholson BD, Turner PJ, Fanshawe TR, Williams AJ, Amirthalingam G, Tonner S, Zambon M, Body R, Davies K, Perera R, de Lusignan S, Hayward GN, and Hobbs FDR
Background and Objective: Point-of-care lateral flow device antigen testing has been used extensively to identify individuals with active SARS-CoV-2 infection in the community. This study aimed to evaluate the diagnostic accuracy of two point-of-care tests (POCTs) for SARS-CoV-2 in routine community care., Methods: Adults and children with symptoms consistent with suspected current COVID-19 infection were prospectively recruited from 19 UK general practices and two COVID-19 testing centres between October 2020 and October 2021. Participants were tested by trained healthcare workers using at least one of two index POCTs (Roche-branded SD Biosensor Standard™ Q SARS-CoV-2 Rapid Antigen Test and/or BD Veritor™ System for Rapid Detection of SARS-CoV-2). The reference standard was laboratory triplex reverse transcription quantitative PCR (RT-PCR) using a combined nasal/oropharyngeal swab. Diagnostic accuracy parameters were estimated, with 95% confidence intervals (CIs), overall, in relation to RT-PCR cycle threshold and in pre-specified subgroups., Results: Of 663 participants included in the primary analysis, 39.2% (260/663, 95% CI 35.5% to 43.0%) had a positive RT-PCR result. The SD Biosensor POCT had sensitivity 84.0% (178/212, 78.3% to 88.6%) and specificity 98.5% (328/333, 96.5% to 99.5%), and the BD Veritor POCT had sensitivity 76.5% (127/166, 69.3% to 82.7%) and specificity 98.8% (249/252, 96.6% to 99.8%) compared with RT-PCR. Sensitivity of both devices dropped substantially at cycle thresholds ≥30 and in participants more than 7 days after onset of symptoms., Conclusions: Both POCTs assessed exceed the Medicines and Healthcare products Regulatory Agency target product profile's minimum acceptable specificity of 95%. Confidence intervals for both tests include the minimum acceptable sensitivity of 80%. In symptomatic patients, negative results on these two POCTs do not preclude the possibility of infection. Tests should not be expected to reliably detect disease more than a week after symptom onset, when viral load may be reduced., Registration: ISRCTN142269., Competing Interests: We have read the journal’s policy and the authors of this manuscript have the following competing interests: The authorship declares funding support for this study from the University of Oxford Medical Sciences Division Benefactors Urgent COVID-19 Fund, the National Institute for Health and Care (NIHR) School of Primary Care Research, and Urgent Public Health funding for the CONDOR Platform from the NIHR and Asthma+Lung UK. The RAPTOR-C19 study team received analysers and assays free of charge from Becton Dickinson for evaluation in this study. GNH declares funding from the National Institute for Health and Care Research (NIHR) paid to the University of Oxford. KD declares grant funding from Alere Inc and Cepheid Inc paid to her institution for unrelated research. TRF declares NIHR support from the NIHR Community Healthcare MIC for diagnostic evaluation research. AJW declares grant funding received by the University of Oxford through a Wellcome Trust Enriching Engagement grant which has supported unrelated patient participation work carried out by the Royal College of General Practitioners Research Surveillance Centre (based at the University of Oxford) for surveillance work. GE declares funding support from the NIHR Community Healthcare MIC recieved by the University of Oxford. AM declares the support of a Wellcome Trust Doctoral Research Fellowship and an NIHR In-practice Fellowship unrelated to this research. PJT declares support from the NIHR Community Healthcare MIC for diagnostic evaluation research. PJT has provided expert support to the Longitude Prize AMR competition administration which is unrelated to this project and for which the University of Oxford received an honorarium. RB declares grant funding for this project from the NIHR and Asthma+Lung UK, with additional funding from the Department of Health and Social Care paid to his host institution. RB declares grants from Siemens Healthineers, Abbott Point-of-Care and Ancon, all paid to his institution for unrelated research. He declares consulting fees received by his institution from Roche, Siemens, Aptamer Group, LumiraDx, Beckman Coulter and Radiometer, with personal fees received from Psyros Diagnostics. RB has received support for attending meetings / travel from Roche and EMCREG International. RB has participated on data safety monitoring boards or advisory boards for the unrelated FORCE Trial, REWIRE Trial, TARGET-CTA, and Magnetocardiography study (MAGNETIC - sponsored by Creavo). RB is the Deputy National Specialty Lead for Trauma & Emergency Care, National Institute for Health and Care Research Clinical Research Network. RB declares receipt of donated reagents for research not detailed in this paper from Roche, LumiraDx, BD, iXensor, Abbott Point-of-Care, Randox, Avacta, Menarini, loan of analysers from Randox and Menarini, and assays run free of charge for research purposes by Chronomics, My110, and Ancon. JJL declares funding from an NIHR Doctoral Research Fellowship which is unrelated to this research. LM declares support from the NIHR Community Healthcare MIC and other NIHR grants to the University of Oxford in support of this work. EL declares unrelated project funding received by the UKHSA Vaccine Evaluation Unit for contract research from GSK, Pfizer and Sanofi. MZ declares her unpaid activities as the Chair of the charitable organisation ISIRV and her membership of the UK SAGE, NERVTAG and JCVI groups. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2023 Nicholson et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)