Accuracy of four lateral flow immunoassays for anti SARS-CoV-2 antibodies: a head-to-head comparative study

Hayley E Jones; Ranya Mulchandani; Sian Taylor-Phillips; A E Ades; Justin Shute; Keith R Perry; Nastassya L Chandra; Tim Brooks; Andre Charlett; Matthew Hickman; Isabel Oliver; Stephen Kaptoge; John Danesh; Emanuele Di Angelantonio; David Wyllie; COMPARE study investigators, EDSAB-HOME investigators

doi:10.1016/j.ebiom.2021.103414

Accuracy of four lateral flow immunoassays for anti SARS-CoV-2 antibodies: a head-to-head comparative study

EBioMedicine. 2021 Jun:68:103414. doi: 10.1016/j.ebiom.2021.103414. Epub 2021 Jun 4.

Authors

Hayley E Jones¹, Ranya Mulchandani², Sian Taylor-Phillips³, A E Ades⁴, Justin Shute², Keith R Perry², Nastassya L Chandra², Tim Brooks², Andre Charlett², Matthew Hickman⁵, Isabel Oliver⁶, Stephen Kaptoge⁷, John Danesh⁷, Emanuele Di Angelantonio⁷, David Wyllie²; COMPARE study investigators, EDSAB-HOME investigators

Affiliations

¹ Population Health Sciences, Bristol Medical School, University of Bristol, UK; NIHR Health Protection Research Unit (HPRU) in Behavioural Science and Evaluation, University of Bristol, UK. Electronic address: hayley.jones@bristol.ac.uk.
² Public Health England, UK.
³ Warwick Medical School, University of Warwick, UK.
⁴ Population Health Sciences, Bristol Medical School, University of Bristol, UK.
⁵ Population Health Sciences, Bristol Medical School, University of Bristol, UK; NIHR Health Protection Research Unit (HPRU) in Behavioural Science and Evaluation, University of Bristol, UK.
⁶ NIHR Health Protection Research Unit (HPRU) in Behavioural Science and Evaluation, University of Bristol, UK; Public Health England, UK.
⁷ Department of Public Health and Primary Care, University of Cambridge, UK.

Abstract

Background: SARS-CoV-2 antibody tests are used for population surveillance and might have a future role in individual risk assessment. Lateral flow immunoassays (LFIAs) can deliver results rapidly and at scale, but have widely varying accuracy.

Methods: In a laboratory setting, we performed head-to-head comparisons of four LFIAs: the Rapid Test Consortium's AbC-19^TM Rapid Test, OrientGene COVID IgG/IgM Rapid Test Cassette, SureScreen COVID-19 Rapid Test Cassette, and Biomerica COVID-19 IgG/IgM Rapid Test. We analysed blood samples from 2,847 key workers and 1,995 pre-pandemic blood donors with all four devices.

Findings: We observed a clear trade-off between sensitivity and specificity: the IgG band of the SureScreen device and the AbC-19^TM device had higher specificities but OrientGene and Biomerica higher sensitivities. Based on analysis of pre-pandemic samples, SureScreen IgG band had the highest specificity (98.9%, 95% confidence interval 98.3 to 99.3%), which translated to the highest positive predictive value across any pre-test probability: for example, 95.1% (95% uncertainty interval 92.6, 96.8%) at 20% pre-test probability. All four devices showed higher sensitivity at higher antibody concentrations ("spectrum effects"), but the extent of this varied by device.

Interpretation: The estimates of sensitivity and specificity can be used to adjust for test error rates when using these devices to estimate the prevalence of antibody. If tests were used to determine whether an individual has SARS-CoV-2 antibodies, in an example scenario in which 20% of individuals have antibodies we estimate around 5% of positive results on the most specific device would be false positives.

Funding: Public Health England.

Keywords: COVID-19; Lateral flow devices; Rapid testing; Seroepidemiology; Serosurveillance.

Publication types

Comparative Study

MeSH terms

Antibodies, Viral / analysis*
COVID-19 / diagnosis*
COVID-19 / immunology
Early Diagnosis
Humans
Immunoassay
Pandemics
Population Surveillance
Prospective Studies
SARS-CoV-2 / immunology*
Sensitivity and Specificity

Substances

Antibodies, Viral

Abstract

Publication types

MeSH terms

Substances

Grants and funding