Background Accurate antibody tests are essential to monitor the SARS-CoV-2 pandemic. Lateral flow immunoassays (LFIAs) can deliver testing at scale. However, reported performance varies, and sensitivity analyses have generally been conducted on serum from hospitalised patients. For use in community testing, evaluation of finger-prick self-tests, in non-hospitalised individuals, is required.
Methods Sensitivity analysis was conducted on 276 non-hospitalised participants. All had tested positive for SARS-CoV-2 by reverse transcription PCR and were ≥21 days from symptom onset. In phase I, we evaluated five LFIAs in clinic (with finger prick) and laboratory (with blood and sera) in comparison to (1) PCR-confirmed infection and (2) presence of SARS-CoV-2 antibodies on two ‘in-house’ ELISAs. Specificity analysis was performed on 500 prepandemic sera. In phase II, six additional LFIAs were assessed with serum.
Findings 95% (95% CI 92.2% to 97.3%) of the infected cohort had detectable antibodies on at least one ELISA. LFIA sensitivity was variable, but significantly inferior to ELISA in 8 out of 11 assessed. Of LFIAs assessed in both clinic and laboratory, finger-prick self-test sensitivity varied from 21% to 92% versus PCR-confirmed cases and from 22% to 96% versus composite ELISA positives. Concordance between finger-prick and serum testing was at best moderate (kappa 0.56) and, at worst, slight (kappa 0.13). All LFIAs had high specificity (97.2%–99.8%).
Interpretation LFIA sensitivity and sample concordance is variable, highlighting the importance of evaluations in setting of intended use. This rigorous approach to LFIA evaluation identified a test with high specificity (98.6% (95%CI 97.1% to 99.4%)), moderate sensitivity (84.4% with finger prick (95% CI 70.5% to 93.5%)) and moderate concordance, suitable for seroprevalence surveys.
- viral infection
- clinical epidemiology
- respiratory infection
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BF and JCB contributed equally.
WSB and GSC contributed equally.
Contributors All listed authors made substantial contributions to the conception or design of the work; or the acquisition, analysis or interpretation of data for the work; and drafting the work or revising it critically for important intellectual content; and final approval of the version to be published; and agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
Funding This work was supported by funding from The Department of Health and Social Care (DHSC) and NIHR Biomedical Research Centre of Imperial College NHS Trust. GC is supported by an NIHR Professorship. WB is the Action Medical Research Professor. AD is an NIHR senior investigator. DA is an Emeritus NIHR Senior Investigator. HW is an NIHR Senior Investigator. RC holds IPR on the hybrid DABA and this work was supported by UKRI/MRC grant (reference is MC_PC_19078). The sponsor is Imperial College London.
Disclaimer The funders had no role in the production of this manuscript.
Competing interests All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.
Patient consent for publication Not required.
Ethics approval The study’s conduct and reporting is fully compliant with the World Medical Association’s Declaration of Helsinki on Ethical Principles for Medical Research Involving Human Subjects. This work was undertaken as part of the REACT 2 study, with ethical approval from South Central–Berkshire B Research Ethics Committee (REC ref: 20/SC/0206; IRAS 283805). Samples for negative controls were taken from the Airwave study approved by North West–Haydock Research Ethics Committee (REC ref: 19/NW/0054).
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement Data are available on reasonable request. All data relevant to the study are included in the article or uploaded as supplementary information. Anonymised data with results of positive/negative individual tests can be provided on request through contact with study team. Email firstname.lastname@example.org; ORCID ID: 0000-0002-2659-544X.
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