Use cases for COVID-19 screening and surveillance with rapid antigen-detecting tests: a systematic review

  1. Apoorva Anand
  2. Jacob Bigio
  3. Emily MacLean
  4. Talya Underwood
  5. Nitika Pant Pai
  6. Sergio Carmona
  7. Samuel G. Schumacher
  8. Amy Toporowski

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Abstract

Introduction

Testing is critical to controlling the COVID-19 pandemic. Antigen-detecting rapid diagnostic tests (Ag-RDTs) that can be used at the point of care have the potential to increase access to COVID-19 testing, particularly in settings with limited laboratory capacity. This systematic review synthesized literature on specific use cases and performance of Ag-RDTs for detecting SARS-CoV-2, for the first comprehensive assessment of Ag-RDT use in real-world settings.

Methods

We searched three databases (PubMed, EMBASE and medRxiv) up to 12 April 2021 for publications on Ag-RDT use for large-scale screening, irrespective of symptoms, and surveillance of COVID-19, excluding studies of only presumptive COVID-19 patients. We tabulated data on the study setting, populations, type of test, diagnostic performance and operational findings. We assessed risk of bias using QUADAS-2 and an adapted tool for prevalence studies.

Results

From 4313 citations, 39 studies conducted in asymptomatic and symptomatic adults were included. Study sample sizes varied from 40 to >5 million. Of 39 studies, 37 (94.9%) investigated lateral flow Ag-RDTs and two (5.1%) investigated multiplex sandwich chemiluminescent enzyme immunoassay Ag-RDTs. Six categories of testing (screening/surveillance) initiatives were identified: mass screening (n=13), targeted screening (n=11), healthcare entry testing (n=6), at-home testing (n=4), surveillance (n=4) and prevalence survey (n=1). Across studies, Ag-RDT sensitivity varied from 40% to 100%. Ag-RDTs were noted as convenient, easy-to-use and low cost, with a rapid turnaround time and high user acceptability. Risk of bias was generally low or unclear across the studies.

Conclusion

This systematic review demonstrates the use of Ag-RDTs across a wide range of real-world settings for screening and surveillance of COVID-19 in both symptomatic and asymptomatic individuals. Ag-RDTs were overall found to be easy-to-use, low cost and rapid tools, when consideration is given to their implementation and interpretation. The review was funded by FIND, the global alliance for diagnostics.

SUMMARY

What is already known?

  • Antigen-detecting rapid diagnostic tests (Ag-RDTs) have the potential to substantially improve access to timely testing for COVID-19 and are being deployed in a variety of settings around the world

  • While studies have investigated the diagnostic accuracy of Ag-RDTs, less is known about how and in what settings Ag-RDTs are being used around the world and their performance in these different settings

What are the new findings?

  • Ag-RDTs are being used in a diverse range of real-world settings for mass screening and surveillance of COVID-19 among symptomatic and asymptomatic individuals

  • The sensitivity of Ag-RDTs is variable - ranging from 40% to 100% - and in some cases low compared with RT-PCR, meaning that the value of testing with Ag-RDTs needs to be carefully evaluated for each use case taking into account factors such as the prevalence of COVID-19 in the population, the consequences of false positive or false negative results, and whether confirmatory testing of positive or negative Ag-RDT results with RT-PCR is required

  • Nevertheless, Ag-RDTs are generally reported as being easy to use and low cost, with a rapid turnaround time that enables timely identification of cases and subsequent interventions to prevent onward transmission of COVID-19

What do the new findings imply?

  • The evidence indicates that Ag-RDTs can be effectively deployed across a broad range of settings when consideration is given to how they are implemented and interpreted

  • The development of more detailed, evidence-based testing policies for Ag-RDTs will be important to help countries implement effective testing programmes and make the best use of Ag-RDTs as part of the COVID-19 testing toolkit

Article activity feed

  1. ScreenIT

    SciScore for 10.1101/2021.11.03.21265807: (What is this?)

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

    Table 1: Rigor

    Ethicsnot detected.
    Sex as a biological variablenot detected.
    RandomizationThe second was surveillance, which included two settings: i) serial or repeat testing of well-defined groups, e.g. students in professional medical training programmes, professional sports franchises (players and staff), and ii) random samples of a large population, all without clinical or epidemiological suspicion of SARS-CoV-2 infection.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Search strategy: Three reviewers (AA, JB, EM) searched two electronic databases of published literature (PubMed, EMBASE) and one preprint database (medRxiv).
    PubMed
    suggested: (PubMed, RRID:SCR_004846)
    EMBASE
    suggested: (EMBASE, RRID:SCR_001650)

    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:
    Some limitations of the approach are that the studies identified from the review are primarily from the USA and Europe, with fewer reports from LMICs. This limits understanding of how Ag-RDTs have been used across LMICs, but may also reflect that Ag-RDTs have been less available for widespread use in LMICs than in high-income countries. Heterogeneity in study design and setting also prevented us from undertaking a meta-analysis and limits the extent to which individual study results can be compared. The search was also restricted to English and French, and did not include the grey literature, which may have excluded certain reports. Nevertheless, the review represents the first comprehensive assessment of how Ag-RDTs have been used in the real world.

    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.

  2. Version published to 10.1101/2021.11.03.21265807v1 on medRxiv