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. 2021 Mar 2:372:n423.
doi: 10.1136/bmj.n423.

SARS-CoV-2 lateral flow assays for possible use in national covid-19 seroprevalence surveys (React 2): diagnostic accuracy study

Maya Moshe  1 , Anna Daunt  2   3 , Barnaby Flower  2   3 , Bryony Simmons  2 , Jonathan C Brown  2 , Rebecca Frise  2 , Rebecca Penn  2 , Ruthiran Kugathasan  2 , Claire Petersen  3 , Helen Stockmann  3 , Deborah Ashby  4 , Steven Riley  4 , Christina Atchison  4 , Graham P Taylor  2 , Sutha Satkunarajah  5 , Lenny Naar  5 , Robert Klaber  3 , Anjna Badhan  2 , Carolina Rosadas  2 , Federica Marchesin  2 , Natalia Fernandez  2 , Macià Sureda-Vives  6 , Hannah Cheeseman  2 , Jessica O'Hara  2 , Robin Shattock  2 , Gianluca Fontana  5 , Scott J C Pallett  7   8 , Michael Rayment  7 , Rachael Jones  7 , Luke S P Moore  2   7 , Hutan Ashrafian  9 , Peter Cherapanov  2   10 , Richard Tedder  2 , Myra McClure  2 , Helen Ward  4 , Ara Darzi  5 , Paul Elliott  3   4   11 , Graham S Cooke  2 , Wendy S Barclay  2   3 ; React study team
Affiliations

SARS-CoV-2 lateral flow assays for possible use in national covid-19 seroprevalence surveys (React 2): diagnostic accuracy study

Maya Moshe et al. BMJ. .

Abstract

Objective: To evaluate the performance of new lateral flow immunoassays (LFIAs) suitable for use in a national coronavirus disease 2019 (covid-19) seroprevalence programme (real time assessment of community transmission 2-React 2).

Design: Diagnostic accuracy study.

Setting: Laboratory analyses were performed in the United Kingdom at Imperial College, London and university facilities in London. Research clinics for finger prick sampling were run in two affiliated NHS trusts.

Participants: Sensitivity analyses were performed on sera stored from 320 previous participants in the React 2 programme with confirmed previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Specificity analyses were performed on 1000 prepandemic serum samples. 100 new participants with confirmed previous SARS-CoV-2 infection attended study clinics for finger prick testing.

Interventions: Laboratory sensitivity and specificity analyses were performed for seven LFIAs on a minimum of 200 serum samples from participants with confirmed SARS-CoV-2 infection and 500 prepandemic serum samples, respectively. Three LFIAs were found to have a laboratory sensitivity superior to the finger prick sensitivity of the LFIA currently used in React 2 seroprevalence studies (84%). These LFIAs were then further evaluated through finger prick testing on participants with confirmed previous SARS-CoV-2 infection: two LFIAs (Surescreen, Panbio) were evaluated in clinics in June-July 2020 and the third LFIA (AbC-19) in September 2020. A spike protein enzyme linked immunoassay and hybrid double antigen binding assay were used as laboratory reference standards.

Main outcome measures: The accuracy of LFIAs in detecting immunoglobulin G (IgG) antibodies to SARS-CoV-2 compared with two reference standards.

Results: The sensitivity and specificity of seven new LFIAs that were analysed using sera varied from 69% to 100%, and from 98.6% to 100%, respectively (compared with the two reference standards). Sensitivity on finger prick testing was 77% (95% confidence interval 61.4% to 88.2%) for Panbio, 86% (72.7% to 94.8%) for Surescreen, and 69% (53.8% to 81.3%) for AbC-19 compared with the reference standards. Sensitivity for sera from matched clinical samples performed on AbC-19 was significantly higher with serum than finger prick at 92% (80.0% to 97.7%, P=0.01). Antibody titres varied considerably among cohorts. The numbers of positive samples identified by finger prick in the lowest antibody titre quarter varied among LFIAs.

Conclusions: One new LFIA was identified with clinical performance suitable for potential inclusion in seroprevalence studies. However, none of the LFIAs tested had clearly superior performance to the LFIA currently used in React 2 seroprevalence surveys, and none showed sufficient sensitivity and specificity to be considered for routine clinical use.

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Conflict of interest statement

Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: support from the Department of Health and Social Care, NIHR Biomedical Research Centre of Imperial College NHS Trust, UK Research and Innovation/Medical Research Council, Francis Crick Institute, Cancer Research UK, the Wellcome Trust, Huo Family Foundation and Imperial College London for the submitted work; PC, MM, and RT hold intellectual property rights on the hybrid DABA; no other relationships or activities that could appear to have influenced the submitted work.

Figures

Fig 1
Fig 1
Timeline and selection process for lateral flow immunoassay (LFIA) evaluation. Further information about flow of participants is included in supplementary figures i and ii. *Biosure (Mologic) II was tested with 5 µL serum (according to instructions provided at time). Manufacturer advises LFIA should be performed with 10 µL serum. React 2=real-time assessment of community transmission 2
Fig 2
Fig 2
Sensitivity of lateral flow immunoassays for finger prick (self-read), finger prick (observer read), matched serum, and initial analysis with serum. S-ELISA data include sensitivity results versus the in-house SARS-CoV-2 S-ELISA; PCR or antibody confirmed data include sensitivity results versus previous confirmed SARS-CoV-2 infection by PCR or formal laboratory antibody test result. PCR=polymerase chain reaction; SARS-CoV-2=severe acute respiratory syndrome coronavirus 2; S-ELISA=spike protein enzyme linked immunoassay
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