Diagnostic accuracy of rapid antigen tests in asymptomatic and presymptomatic close contacts of individuals with confirmed SARS-CoV-2 infection: cross sectional study

  1. Ewoud Schuit
  2. Irene K Veldhuijzen
  3. Roderick P Venekamp
  4. Wouter van den Bijllaardt
  5. Suzan D Pas
  6. Esther B Lodder
  7. Richard Molenkamp
  8. Corine H GeurtsvanKessel
  9. Jans Velzing
  10. Robin C Huisman
  11. Lieke Brouwer
  12. Timo L Boelsums
  13. Gregorius J Sips
  14. Kimberly S M Benschop
  15. Lotty Hooft
  16. Janneke H H M van de Wijgert
  17. Susan van den Hof
  18. Karel G M Moons

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Abstract

Objective

To assess the diagnostic test accuracy of two rapid antigen tests in asymptomatic and presymptomatic close contacts of people with SARS-CoV-2 infection on day 5 after exposure.

Design

Prospective cross sectional study.

Setting

Four public health service covid-19 test sites in the Netherlands.

Participants

4274 consecutively included close contacts (identified through test-and-trace programme or contact tracing app) aged 16 years or older and asymptomatic for covid-19 when requesting a test.

Main outcome measures

Sensitivity, specificity, and positive and negative predictive values of Veritor System (Beckton Dickinson) and Biosensor (Roche Diagnostics) rapid antigen tests, with reverse-transcriptase polymerase chain reaction (RT-PCR) testing as reference standard. The viral load cut-off above which 95% of people with a positive RT-PCR test result were virus culture positive was used as a proxy of infectiousness.

Results

Of 2678 participants tested with Veritor, 233 (8.7%) had a RT-PCR confirmed SARS-CoV-2 infection of whom 149 were also detected by the rapid antigen test (sensitivity 63.9%, 95% confidence interval 57.4% to 70.1%). Of 1596 participants tested with Biosensor, 132 (8.3%) had a RT-PCR confirmed SARS-CoV-2 infection of whom 83 were detected by the rapid antigen test (sensitivity 62.9%, 54.0% to 71.1%). In those who were still asymptomatic at the time of sampling, sensitivity was 58.7% (51.1% to 66.0%) for Veritor (n=2317) and 59.4% (49.2% to 69.1%) for Biosensor (n=1414), and in those who developed symptoms were 84.2% (68.7% to 94.0%; n=219) for Veritor and 73.3% (54.1% to 87.7%; n=158) for Biosensor. When a viral load cut-off was applied for infectiouness (≥5.2 log10 SARS-CoV-2 E gene copies/mL), the overall sensitivity was 90.1% (84.2% to 94.4%) for Veritor and 86.8% (78.1% to 93.0%) for Biosensor, and 88.1% (80.5% to 93.5%) for Veritor and 85.1% (74.3% to 92.6%) for Biosensor, among those who remained asymptomatic throughout. Specificities were >99%, and positive and negative predictive values were >90% and >95%, for both rapid antigen tests in all analyses.

Conclusions

The sensitivities of both rapid antigen tests in asymptomatic and presymptomatic close contacts tested on day 5 onwards after close contact with an index case were more than 60%, increasing to more than 85% after a viral load cut-off was applied as a proxy for infectiousness.

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  1. Version published to 10.1136/bmj.n1676
  2. ScreenIT

    SciScore for 10.1101/2021.03.18.21253874: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: Ethical review: The Medical Ethics Review Committee (METC) Utrecht concluded that ethics approval was not required because the study is outside the scope of the Dutch Medical Research Involving Human Subjects Act (protocol number: 20/750).
    Consent: All participants signed an informed consent form prior to any study procedure.
    Randomizationnot detected.
    BlindingBoth Ag-RDT were applied according to manufacturer instructions with one exception: BD results were determined visually instead of using a BD Veritor Plus Analyzer. Interpretation of Ag-RDTs was always done prior to (thus blinded for) RT-PCR.
    Power AnalysisWe based our sample size calculation on an expected sensitivity of 80%, with a margin of error of 7%, type I error of 5% and power of 90%.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    At the Erasmus MC Viroscience diagnostic laboratory, samples of participants with a positive RT-PCR test result were cultured for seven days, and, once cytopathic effects (CPE) were visible, the presence of SARS-CoV-2 was confirmed with immunofluorescent detection of SARS-CoV-2 nucleocapsid protein (Rabbit polyclonal antibody, Sino Biological inc.), Eschborn, Germany) (Supplementary Material 2).
    SARS-CoV-2 nucleocapsid protein
    suggested: None

    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:
    Our study also has some potential limitations. First, although we aimed to sample pre-/asymptomatic individuals at five days after exposure to an index case, 12% was sampled before the fifth day since last contact. It is known that the accuracy of the RT-PCR reference test is not yet optimal before the fifth day after contact with an index case 6. Interestingly though, our stratified analysis indicated that the RT-PCR positivity fraction was actually higher in close contacts who were sampled before the fifth day since last contact. We hypothesize that some of these individuals have had prolonged contact with the index case, for example because they live in the same household. Close contacts living in the same household on average test more often positive compared to non-household close contacts (20% vs. 10%) 16. This would also explain why these close contacts reported to have contact with the index case less than 5 days ago, as the last contact with an infected household member could be the same day of testing. A second limitation is that virus culture was only available in one of the two central laboratories. Hence, the assumed infectiousness viral load cut-off was extrapolated to the second laboratory. Reassuringly, the RT-PCR calibration curves of both laboratories indicated that Ct values corresponded to similar viral loads in both laboratories. A correlation between infectivity in culture and viral load of the specimen as well as negative associations between lower vira...

    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.

    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 10.1101/2021.03.18.21253874 on medRxiv