Characteristics of SARS-CoV-2 testing for rapid diagnosis of COVID-19 during the initial stages of a global pandemic

  1. Jennifer L. Guthrie
  2. Allison J. Chen
  3. Dalton R. Budhram
  4. Kirby Cronin
  5. Adriana Peci
  6. Paul Nelson
  7. Gustavo V. Mallo
  8. George Broukhanski
  9. Michelle Murti
  10. Anna Majury
  11. Tony Mazzulli
  12. Vanessa G. Allen
  13. Samir N. Patel
  14. Julianne V. Kus
  15. Vanessa Tran
  16. Jonathan B. Gubbay

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Abstract

Accurate SARS-CoV-2 diagnosis is essential to guide prevention and control of COVID-19. Here we examine SARS-CoV-2 molecular-based test performance characteristics and summarize case-level data related to COVID-19 diagnosis. From January 11 through April 22, 2020, Public Health Ontario conducted SARS-CoV-2 testing of 86,942 specimens collected from 80,354 individuals, primarily using real-time reverse-transcription polymerase chain reaction (rRT-PCR) methods. We analyzed test results across specimen types and for individuals with multiple same-day and multi-day collected specimens. Nasopharyngeal compared to throat swabs had a higher positivity (8.8% vs. 4.8%) and an adjusted estimate 2.9 C t lower (SE = 0.5, p <0.001). Same-day specimens showed high concordance (98.8%), and the median C t of multi-day specimens increased over time. Symptomatic cases had rRT-PCR results with an adjusted estimate 3.0 C t (SE = 0.5, p <0.001) lower than asymptomatic/pre-symptomatic cases. Overall test sensitivity was 84.6%, with a negative predictive value of 95.5%. Molecular testing is the mainstay of SARS-CoV-2 diagnosis and testing protocols will continue to be dynamic and iteratively modified as more is learned about this emerging pathogen.

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  1. Version published to 10.1371/journal.pone.0253941
  2. ScreenIT

    SciScore for 10.1101/2020.12.23.20231589: (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

    No key resources detected.

    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 has several limitations. First, reported sensitivity and NPV should be interpreted with caution as our analysis does not compare two distinct tests, and instead uses an individual’s collective test results within a 7 day period (“true positive” result) as a comparison for their initial test result. Therefore, sensitivity was dependent on the time period used as a discrete episode. Current literature reports a 5 day mean incubation with viral shedding a few days before symptom onset. Thus, we defined an episode as 7 days following initial specimen collection, and found our calculation of test sensitivity to be consistent with the literature(2); however, our NPV estimate was higher than other reports(26). As it is more likely for persons with high pre-test probability to be retested, there may be a bias towards an underestimation of the true sensitivity. The nature of this method does not allow for calculation of specificity and PPV. Second, a limitation of many COVID-19 studies at this time, including this one, is that recommendations regarding who should be tested changed over the study period and may have impacted which individuals were prioritized for testing. Thus, our results may not be representative of all cases, particularly asymptomatic or hospitalized individuals, and may not be generalizable to all locations. Last, drawing conclusions regarding the asymptomatic/pre-symptomatic infected population is difficult within this study population owing to limited d...

    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 10.1101/2020.12.23.20231589 on medRxiv