The diagnostic accuracy of isothermal nucleic acid point-of-care tests for human coronaviruses: A systematic review and meta-analysis

  1. Pakpoom Subsoontorn
  2. Manupat Lohitnavy
  3. Chuenjid Kongkaew

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Abstract

Many recent studies reported coronavirus point-of-care tests (POCTs) based on isothermal amplification. However, the performances of these tests have not been systematically evaluated. Cochrane Handbook for Systematic Reviews of Diagnostic Test Accuracy was used as a guideline for conducting this systematic review. We searched peer-reviewed and preprint articles in PubMed, BioRxiv and MedRxiv up to 28 September 2020 to identify studies that provide data to calculate sensitivity, specificity and diagnostic odds ratio (DOR). Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) was applied for assessing quality of included studies and Preferred Reporting Items for a Systematic Review and Meta-analysis of Diagnostic Test Accuracy Studies (PRISMA-DTA) was followed for reporting. We included 81 studies from 65 research articles on POCTs of SARS, MERS and COVID-19. Most studies had high risk of patient selection and index test bias but low risk in other domains. Diagnostic specificities were high (> 0.95) for included studies while sensitivities varied depending on type of assays and sample used. Most studies (n = 51) used reverse transcription loop-mediated isothermal amplification (RT-LAMP) to diagnose coronaviruses. RT-LAMP of RNA purified from COVID-19 patient samples had pooled sensitivity at 0.94 (95% CI: 0.90–0.96). RT-LAMP of crude samples had substantially lower sensitivity at 0.78 (95% CI: 0.65–0.87). Abbott ID Now performance was similar to RT-LAMP of crude samples. Diagnostic performances by CRISPR and RT-LAMP on purified RNA were similar. Other diagnostic platforms including RT- recombinase assisted amplification (RT-RAA) and SAMBA-II also offered high sensitivity (> 0.95). Future studies should focus on the use of un-bias patient cohorts, double-blinded index test and detection assays that do not require RNA extraction.

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  1. Version published to 10.1038/s41598-020-79237-7
  2. ScreenIT

    SciScore for 10.1101/2020.07.09.20150235: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Search strategy: Peer-reviewed articles were searched on PubMed from its inception up to 16 June 2020 with the following search terms: (coronavirus OR COVID-19 OR severe acute respiratory syndrome OR middle east respiratory syndrome) AND (rapid diagnosis OR isothermal amplification).
    PubMed
    suggested: (PubMed, RRID:SCR_004846)
    Preprint articles were searched on BioRxiv and MedRxiv from 1 January 2020 to 16 June 2020 using a search term ‘isothermal amplification’.
    BioRxiv
    suggested: (bioRxiv, RRID:SCR_003933)

    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:
    Future work should provide this information in order to allow better assessment of diagnosis test performance and identify their actual limitations. No published study thus far directly compared the Cororavirus detection accuracy of CRISPR diagnosis to that of RT-LAMP. Subgroup analysis showed that, for purified RNA samples, ln(DOR) of CRISPR diagnosis is only slightly higher than that of RT-LAMP (ln(DOR) within 95% CI of each other) (Fig 4A, 5A). Additionally, reported limits of detection of these CRISPR diagnosis tests (7.3-100 copies/reaction) are within the same range as that of RT-LAMP (2-120 copies/reaction) (Table 1). Given available data, it cannot be concluded that CRISPR diagnosis can outperform RT-LAMP at least for purified RNA samples. Existing CRISPR diagnosis also requires RT-LAMP or other isothermal techniques to pre-amplify nucleic acid targets before CRISPR detection. The use of cas12 or cas13 enzyme adds to the cost of CRISPR diagnosis test kit, making it likely to be more expensive than RT-LAMP. Future study should directly compare and highlight unique strength of CRISPR diagnosis relative other isothermal techniques, for example, its ability for multiplex detection and identifying single base difference in targeted genomes [70-72]. Our systematic review and meta-analysis also included one study each on diagnosis accuracy of RT-iiPCR, RCA and RT-RAA using purified RNA samples. The two studies using RCA and RT-iiPCR reported perfect or near perfect sensitivi...

    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

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  3. Version published to 10.1101/2020.07.09.20150235v1 on medRxiv