Can the Rapid Antigen Test for COVID-19 Replace RT-PCR: A Meta-analysis of Test Agreement

  1. Ibrahim Elmakaty
  2. Abdelrahman Elsayed
  3. Rama Ghassan Hommos
  4. Ruba Abdo
  5. Amira Mohamed
  6. Zahra Yousif
  7. Maryam Fakhroo
  8. Abdulrahman Alansari
  9. Peter V. Coyle
  10. Suhail A. R. Doi

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Abstract

Background

Several studies have compared the performance of reverse transcription-polymerase chain reaction (RT-PCR) and antigen rapid diagnostic tests (Ag-RDTs) as tools to diagnose SARS-CoV-2 disease (COVID-19). As the performance of Ag-RDT may vary among different products and viral load scenarios, the clinical utility of the Ag-RDT remains unclear. Our aim is to assess the diagnostic agreement between Ag-RDTs and RT-PCR in testing for COVID-19 across different products and cycle threshold (Ct) values.

Methods

An evidence synthesis and meta-analysis of Positive Percent Agreement (PPA) and Negative Percent Agreement (NPA) was conducted after an exhaustive search of five databases to locate published studies that compared Ag-RDT to RT-PCR and reported quantitative comparison results. After the screening, quality assessment, and data extraction, the synthesis of pooled estimates was carried out utilizing the quality-effects (QE) model and Freeman-Tukey double arcsine transformation (FTT) for variance stabilization. Subgroup analysis was also conducted to evaluate the tests’ diagnostic agreement across distinctive products and Ct-value thresholds.

Findings

A total of 420 studies were screened by title and abstract, of which 39 were eventually included in the analysis. The overall NPA was 99.4% (95%CI 98.8-99.8, I 2 =91.40%). The PPA was higher in lower Ct groups such as groups with Ct <20 and Ct <25, which had an overall PPA of 95.9% (95%CI 92.7-98.2, I 2 =0%) and 96.8% (95%CI 95.2-98.0, I 2 =50.1%) respectively. This is in contrast to groups with higher Ct values, which had relatively lower PPA. Panbio and Roche Ag-RDTs had the best consistent overall PPA across different Ct groups especially in groups with Ct <20 and Ct <25.

Interpretation

The findings of our meta-analysis support the use of Ag-RDTs in lieu of RT-PCR for decision making regarding COVID-19 control measures, since the enhanced capacity of RT-PCR to detect disease in those that are Ag-RDT negative will be unlikely to have much public health utility. This step will drastically reduce the cost and time in testing for COVID-19.

Funding

This research did not receive any specific funding.

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  1. ScreenIT

    SciScore for 10.1101/2021.10.19.21265190: (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.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    An extensive search strategy was designed to retrieve all relevant articles published in PubMed up to 15 Mar 2021, using the following MeSH terms: “COVID-19” AND “Immunoassay” AND “Reverse Transcriptase Polymerase Chain Reaction”.
    PubMed
    suggested: (PubMed, RRID:SCR_004846)
    MeSH
    suggested: (MeSH, RRID:SCR_004750)
    To ensure comprehensiveness, other databases such as Embase, Google Scholar, EBSCO, and Scopus were similarly searched for additional relevant articles.
    Embase
    suggested: (EMBASE, RRID:SCR_001650)
    Google Scholar
    suggested: (Google Scholar, RRID:SCR_008878)

    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:
    This drop-off may actually be an advantage rather than a limitation of the Ag-RDT since it has been reported that high Ct-value has a reduced chance of successful culture and of being contagious,68 which has been shown to be between Ct ranging from 24–30.69,70 This suggests that individuals start being more contagious at the threshold where the Ag-RDT operates best. Therefore, in case an Ag-RDT fails to detect an infected individual of Ct >25, it is likely that the individual is either noncontagious or is in early infection, which can be resolved by re-testing on subsequent days for contacts of a documented case. In our study, we considered the RT-PCR to be a reference test, rather than a gold standard as done by previous meta-analyses targeting the same topic. This makes our study the first meta-analysis to have presented the PPA and NPA of Ag-RDTs, which is a primary strength of this study and allows interpretation of results for decision-makers. In addition, we used robust methodologies19 and broad yet specific selection criteria. It is also important to note that although this is an agreement study, we have found QUADAS-216 to be suitable for quality assessment of diagnostic agreement studies with only the exclusion of a single safeguard. There are a few limitations to our meta-analysis that should be mentioned. To begin with, not enough studies have stratified their analysis based on Ct-value, which resulted in data limitation clearly shown in our results. An example wou...

    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.

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