Bean extract-based gargle for efficient diagnosing COVID-19 at early-stage using rapid antigen tests : a clinical, prospective, diagnostic study

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Abstract

Importance

The antigen-based rapid diagnostic test (Ag-RDT), using saliva specimens, is fast, non-invasive and suitable for SARS-CoV-2 self-testing, unlike nasopharyngeal swab (NPS) testing.

Objective

To assess the diagnostic sensitivity of a novel Beanguard gargle™ (BG)-based virus detection method for early diagnosis of COVID-19.

Design

This clinical trial was conducted at Gunsan Medical Center, Namwon Medical Center, and Jeonbuk National University Hospital, between May 7 and July 7, 2021.

Setting

Paired NPS and BG-based saliva specimens collected from COVID-19 patients and healthy individuals were analyzed using NPS-RT-PCR, BG-RT-PCR, and BG-Ag-RDTs.

Participants

The study comprised 102 COVID-19-positive patients hospitalized after governmental screening process and 100 healthy individuals. Forty-five COVID-19 patients were sampled within 6 days of illness and 57 within 7–15 days; 27 were categorized as asymptomatic and 75, as symptomatic. Eight and 2 patients carried the SARS-CoV-2 Alpha and Delta variants, respectively.

Intervention

The diagnostic performances of BG-Ag-RDT, BG-RT-PCR, and NPS-RT-PCR for detecting SARS-CoV-2 were compared.

Main outcomes

The sensitivities of BG-Ag-RDT and BG-RT-PCR towards salivary viral detection were highly concordant, with no discrimination between symptomatic, asymptomatic, or SARS-CoV-2 variant cases.

Results

Among total participants (mean age, 43.7 years), 51% were women. BG-Ag-RDTs showed high sensitivity (97.8%, [95% CI, 88.4% to 99.6%]) and specificity (100%, [95% CI, 96.3% to 100%) in 45 patients within 6 days of illness and could detect all cases of SARS-CoV-2 Alpha and Delta variants. In 11 asymptomatic early-stage cases, both BG-Ag-RDTs and BG-RT-PCR showed excellent sensitivity and specificity of 100% (95% CI, 74.1% to 100% and 95% CI, 20.7% to 100%, respectively). The interaction between SARS-CoV-2 spike proteins and truncated canavalin, an active ingredient from bean extract (BE) and the ultrastructural features of SARS-CoV-2 particles coated with BE were observed. The detachment of the SARS-CoV-2 receptor-binding domain from hACE2 increased as the BE concentration increased, allowing the release of the virus from hACE2 for early diagnosis.

Conclusions and Relevance

Using BG-based saliva remarkably enhances the Ag-RDT diagnostic performance as an alternative to NPS and enables rapid and accurate COVID-19 self-testing and mass screening, supporting efficient COVID-19 management.

Trial Registration

KCT0006438

Key Points

Question

How can we collect SARS-CoV-2 from oral cavity to improve the sensitivity of antigen-based rapid diagnostic test (Ag-RDT)?

Findings

In this clinical study involving 102 hospitalized COVID-19 patients, the Ag-RDT test using Beanguard gargle™-based saliva specimens showed significantly enhanced sensitivity and specificity towards detection of SARS-CoV-2 along with Alpha and Delta variants in all patients tested within 6 days of illness.

Meaning

Our self-testing method represents an attractive alternative to nasopharyngeal swab RT-PCR for the early diagnosis of symptomatic and asymptomatic COVID-19 cases.

Article activity feed

  1. SciScore for 10.1101/2021.08.13.21261463: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: Ethical approval for the study was granted by the Institutional Review Board of Jeonbuk National University
    Consent: Hospital (CUH 2021-04-036-002) and written informed consent statements were obtained from all participants.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power AnalysisMinimal sample size was calculated with 90 percent power at a significance level of 0.05 for the estimated sensitivity and specificity, according to the equation:Where, Z(1-α)/2 and Z1-β are Z-values for the corresponding level of confidence and the desired power, respectively.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Statistical analysis: All statistical analyses were performed using GraphPad Prism v.7, and statistical multiple comparisons were performed using one-way ANOVA followed by post hoc Dunnett’s test.
    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: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    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.