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.

Keywords: COVID-19; Coronavirus; LFD; Lateral flow; Lateral flow tests; Lateralflow devices; National evaluation; Public health; SARS-CoV-2; Testing; United kingdom; VIral antigen detection.

Fig. 1

A. Logistic curves showing association between viral detection/sensitivity and viral load (RNA copies/ml) for Abbott, Deepblue, Orientgene LFDs when performed by Lab worker. B. Logistic curve showing association between viral antigen detection/sensitivity and viral load (RNA copies/mL and Ct) for Innova LFD when performed by trained laboratory scientists and trained healthcare workers.

Fig. 2

Effect of training and operator on the viral detection/sensitivity of the Innova LFD in COVID-19 PCR-positive patients. Whiskers represent 95% confidence intervals.