Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody lateral flow assay for antibody prevalence studies following vaccination: a diagnostic accuracy study

  1. Alexandra Cann
  2. Candice Clarke
  3. Jonathan Brown
  4. Tina Thomson
  5. Maria Prendecki
  6. Maya Moshe
  7. Anjna Badhan
  8. Bryony Simmons
  9. Bob Klaber
  10. Paul Elliott
  11. Ara Darzi
  12. Steven Riley
  13. Deborah Ashby
  14. Paul Martin
  15. Sarah Gleeson
  16. Michelle Willicombe
  17. Peter Kelleher
  18. Helen Ward
  19. Wendy S. Barclay
  20. Graham S. Cooke

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Abstract

Background: Lateral flow immunoassays (LFIAs) are able to achieve affordable, large scale antibody testing and provide rapid results without the support of central laboratories. As part of the development of the REACT programme extensive evaluation of LFIA performance was undertaken with individuals following natural infection. Here we assess the performance of the selected LFIA to detect antibody responses in individuals who have received at least one dose of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine.

Methods: This was a prospective diagnostic accuracy study. Sampling was carried out at renal outpatient clinic and healthcare worker testing sites at Imperial College London NHS Trust. Two cohorts of patients were recruited; the first was a cohort of 108 renal transplant patients attending clinic following two doses of SARS-CoV-2 vaccine, the second cohort comprised 40 healthcare workers attending for first SARS-CoV-2 vaccination and subsequent follow up. During the participants visit, finger-prick blood samples were analysed on LFIA device, while paired venous sampling was sent for serological assessment of antibodies to the spike protein (anti-S) antibodies. Anti-S IgG was detected using the Abbott Architect SARS-CoV-2 IgG Quant II CMIA. A total of 186 paired samples were collected. The accuracy of Fortress LFIA in detecting IgG antibodies to SARS-CoV-2 compared to anti-spike protein detection on Abbott Assay

Results: The LFIA had an estimated sensitivity of 92.0% (114/124; 95% confidence interval [CI] 85.7% to 96.1%) and specificity of 93.6% (58/62; 95% CI 84.3% to 98.2%) using the Abbott assay as reference standard (using the threshold for positivity of 7.10 BAU/ml)

Conclusions: Fortress LFIA performs well in the detection of antibody responses for intended purpose of population level surveillance but does not meet criteria for individual testing.

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  1. Version published to 10.12688/wellcomeopenres.17231.2
  2. ScreenIT

    SciScore for 10.1101/2021.07.14.21260488: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    EthicsConsent: All patients provided written informed consent.
    IRB: The study was approved by the Health Research Authority, Research Ethics Committee (Reference: 20/WA/0123).
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Serological testing: Serological assessment was performed on the Abbott Architect SARS-CoV-2 IgG Quant II CMIA which reports a quantitative anti-Spike antibody titre.
    anti-Spike
    suggested: None
    Serological testing: Spike protein antibodies (anti-S) were detected using the Abbott Architect SARS-CoV-2 IgG Quant II CMIA.
    anti-S
    suggested: None
    Performance Analysis: The primary outcome of the study was sensitivity and specificity of each LFIA in detecting SARS-CoV-2 IgG antibodies.
    SARS-CoV-2 IgG
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    The ability of sera to neutralise SARS-CoV-2 virus was assessed by neutralisation assay on Vero cells.
    Vero
    suggested: CLS Cat# 605372/p622_VERO, RRID:CVCL_0059)
    Sera were serially diluted in OptiPRO SFM (Life Technologies) and incubated for 1h at room temperature with 100 TCID50/well of SARS-CoV-2/England/IC19/2020 and transferred to 96-well plates preseeded with Vero-E6 cells.
    Vero-E6
    suggested: None
    Software and Algorithms
    SentencesResources
    Serological testing: Serological assessment was performed on the Abbott Architect SARS-CoV-2 IgG Quant II CMIA which reports a quantitative anti-Spike antibody titre.
    Abbott Architect
    suggested: (Abbott ARCHITECT i1000sr System, RRID:SCR_019328)
    Statistical analyses were performed with MedCalc.
    MedCalc
    suggested: (MedCalc, RRID:SCR_015044)
    Graphical analyses was performed using GraphPad Prism 9.1.2 software.
    GraphPad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    In terms of study limitations it is important to note that, although the LFIAs were self-tested in the clinic or vaccination centre, participants had access to support from trained healthcare professionals when required. This does not fully replicate the ‘real-world’ application of LFIAs where users will be following a detailed guide in their own homes. Furthermore, the patient cohort includes healthcare workers and as such may demonstrate a greater affinity for self-testing than members of the general population. However, the primary purpose of this study was to evaluate the diagnostics accuracy of the test. The performance of the LFIA evaluated is sufficiently good that it can continue to play a helpful role in the assessment of population antibody responses resulting from widespread infection and high levels vaccination coverage, particularly given the correlation of LFIA results with the functional measure of live virus neutralisation. Over time, antibody titres will begin to wane and ongoing population surveillance may have a helpful role in informing decisions on priority groups and timing of booster vaccines.

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    Results from scite Reference Check: We found no unreliable references.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  3. Version published to 10.1101/2021.07.14.21260488v1 on medRxiv