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Accuracy of UK Rapid Test Consortium (UK-RTC) “AbC-19 Rapid Test” for detection of previous SARS-CoV-2 infection in key workers: test accuracy study

BMJ 2020; 371 doi: https://doi.org/10.1136/bmj.m4262 (Published 11 November 2020) Cite this as: BMJ 2020;371:m4262

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Testing for antibodies to SARS-CoV-2

  1. Ranya Mulchandani, Field Epidemiology Training Programme (UK-FETP) fellow1*,
  2. Hayley E Jones, senior lecturer2*,
  3. Sian Taylor-Phillips, professor3,
  4. Justin Shute, biomedical scientist1,
  5. Keith Perry, clinical scientist1,
  6. Shabnam Jamarani, technical manager1,
  7. Tim Brooks, consultant microbiologist1,
  8. Andre Charlett, head of statistics and modelling1,
  9. Matthew Hickman, professor2,
  10. Isabel Oliver, director of National Infection Service1,
  11. Stephen Kaptoge, principal research associate4,
  12. John Danesh, professor4,
  13. Emanuele Di Angelantonio, professor4,
  14. Anthony E Ades, professor2,
  15. David H Wyllie, consultant microbiologist1
  16. on behalf of the EDSAB-HOME and COMPARE Investigators
    1. 1Public Health England, London, UK
    2. 2University of Bristol, Bristol, UK
    3. 3University of Warwick, Coventry, UK
    4. 4University of Cambridge, Cambridge, UK
    5. *Contributed equally
    1. Correspondence to: D Wyllie David.wyllie{at}phe.gov.uk (or @davidwyllie20 on Twitter)
    • Accepted 2 November 2020

    Abstract

    Objective To assess the accuracy of the AbC-19 Rapid Test lateral flow immunoassay for the detection of previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

    Design Test accuracy study.

    Setting Laboratory based evaluation.

    Participants 2847 key workers (healthcare staff, fire and rescue officers, and police officers) in England in June 2020 (268 with a previous polymerase chain reaction (PCR) positive result (median 63 days previously), 2579 with unknown previous infection status); and 1995 pre-pandemic blood donors.

    Main outcome measures AbC-19 sensitivity and specificity, estimated using known negative (pre-pandemic) and known positive (PCR confirmed) samples as reference standards and secondly using the Roche Elecsys anti-nucleoprotein assay, a highly sensitive laboratory immunoassay, as a reference standard in samples from key workers.

    Results Test result bands were often weak, with positive/negative discordance by three trained laboratory staff for 3.9% of devices. Using consensus readings, for known positive and negative samples sensitivity was 92.5% (95% confidence interval 88.8% to 95.1%) and specificity was 97.9% (97.2% to 98.4%). Using an immunoassay reference standard, sensitivity was 94.2% (90.7% to 96.5%) among PCR confirmed cases but 84.7% (80.6% to 88.1%) among other people with antibodies. This is consistent with AbC-19 being more sensitive when antibody concentrations are higher, as people with PCR confirmation tended to have more severe disease whereas only 62% (218/354) of seropositive participants had had symptoms. If 1 million key workers were tested with AbC-19 and 10% had actually been previously infected, 84 700 true positive and 18 900 false positive results would be projected. The probability that a positive result was correct would be 81.7% (76.8% to 85.8%).

    Conclusions AbC-19 sensitivity was lower among unselected populations than among PCR confirmed cases of SARS-CoV-2, highlighting the scope for overestimation of assay performance in studies involving only PCR confirmed cases, owing to “spectrum bias.” Assuming that 10% of the tested population have had SARS-CoV-2 infection, around one in five key workers testing positive with AbC-19 would be false positives.

    Study registration ISRCTN 56609224.

    Footnotes

    • Contributors: RM, HEJ, STP, TB, MH, IO, and DW planned the study. SK, JD, EDA, and DW planned the specificity investigations. KP and JS planned the laboratory based investigation. KP, JS, SN, JH, AG, HG, and SJ conducted experiments. DW, RM, EDSAB-HOME investigators, and COMPARE investigators collected samples. RB, EL, and TB collated samples and performed assays. HEJ, AEA, RM, SK, and DW did the statistical analyses. RM, HEJ, STP, AEA, and DW wrote the paper. RM and HEJ contributed equally. The corresponding author attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted. DW is the guarantor.

    • Funding: The study was commissioned by the UK Government’s Department of Health and Social Care. It was funded and implemented by Public Health England, supported by the National Institute for Health Research (NIHR) Clinical Research Network (CRN) Portfolio. The Department of Health and Social Care received a report containing these data on 10/9/2020, but had no role in the study design, data collection, analysis, interpretation of results, writing of the manuscript, or the decision to publish. DW acknowledges support from the NIHR Health Protection Research Unit in Genomics and Data Enabling at the University of Warwick. HEJ, AEA, MH, and IO acknowledge support from the NIHR Health Protection Research Unit in Behavioural Science and Evaluation at University of Bristol. STP is supported by an NIHR Career Development Fellowship (CDF-2016-09-018). Participants in the COMPARE Study were recruited with the active collaboration of NHS Blood and Transplant (NHSBT) England (www.nhsbt.nhs.uk). Funding for COMPARE was provided by NHSBT and the NIHR Blood and Transplant Research Unit (BTRU) in Donor Health and Genomics (NIHR BTRU-2014-10024). The academic coordinating centre for COMPARE was supported by core funding from: NIHR BTRU, UK Medical Research Council (MR/L003120/1), British Heart Foundation (RG/13/13/30194), and the NIHR (Cambridge Biomedical Research Centre at the Cambridge University Hospitals NHS Foundation Trust). This work was supported by Health Data Research UK, which is funded by the UK Medical Research Council, Engineering and Physical Sciences Research Council, Economic and Social Research Council, Department of Health and Social Care (England), Chief Scientist Office of the Scottish Government Health and Social Care Directorates, Health and Social Care Research and Development Division (Welsh Division), Public Health Agency (Northern Ireland), British Heart Foundation, and Wellcome. JD holds a British Heart Foundation professorship and an NIHR senior investigator award. The views expressed are those of the author(s) and not necessarily those of the NHS, NIHR, or Department of Health and Social Care.

    • Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: funding for the study as described above; TB has received grants from the UK Government, HEJ has received grants from PHE/NIHR, and STP has received grants from NIHR during the conduct of the study; outside of this work, RB and EL perform meningococcal contract research on behalf of PHE for GSK, Pfizer, and Sanofi Pasteur, MH has received personal fees from Gilead and MSF, SJ and JD have received grants from Merck, Novartis, Pfizer, and AstraZeneca and personal fees and non-financial support from Pfizer Population Research Advisory Panel, and JS and KP report financial activities on behalf of WHO in 2018 and 2019 in evaluation of several other rapid test kits; no other relationships or activities that could appear to have influenced the submitted work.

    • Ethical approval: The EDSAB-HOME study was approved by the NHS Research Ethics Committee (Health Research Authority, IRAS 284980) on 2 June 2020 and the PHE Research Ethics and Governance Group (REGG, NR0198) on 21 May 2020. EDSAB-HOME is registered at http://www.isrctn.com/ISRCTN56609224. Ethical approval for use of the samples from COMPARE is covered by NHS Research Ethics Committee Cambridge East (18/12/2015; ref 15/EE/0335). COMPARE is registered at http://www.isrctn.com/ISRCTN90871183. All participants gave written informed consent.

    • Data sharing: Data are available on reasonable request to the corresponding author.

    • The manuscript’s guarantor affirms that this manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.

    • Dissemination to participants and related patient and public communities: Links to this work will be included on the study website (https://www.gov.uk/government/publications/evaluating-detection-of-sars-cov-2-antibodies-at-home-study), and participants will be alerted that the work has been published.

    • Provenance and peer review: Not commissioned; externally peer reviewed.

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