Sars-Cov-2 antigen tests predict infectivity based on viral culture: comparison of antigen, PCR viral load, and viral culture testing on a large sample cohort

  1. James E. Kirby
  2. Stefan Riedel
  3. Sanjucta Dutta
  4. Ramy Arnaout
  5. Annie Cheng
  6. Sarah Ditelberg
  7. Donald J. Hamel
  8. Charlotte A. Chang
  9. Phyllis J. Kanki

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Abstract

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  1. Version published to 10.1016/j.cmi.2022.07.010
  2. ScreenIT

    SciScore for 10.1101/2021.12.22.21268274: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: Human subjects research in this study was approved by the Institutional Review Boards at Beth Israel Deaconess Medical Center and the Harvard T.H. Chan School of Public Health.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Experimental Models: Cell Lines
    SentencesResources
    RT-qPCR testing: SARS-CoV-2 RT-qPCR testing of samples and Vero cell culture supernatants was performed using the Abbott Molecular M2000 Real-Time or Alinity m SARS-CoV-2 assays according to the manufacturer’s instructions.
    Vero
    suggested: None
    SARS-CoV-2 viral culture: Vero E6 (ATCC CRL-1586) cells were seeded on a 6-well flat bottom plate at 0.3 × 106 cells per well in Eagle’s minimum essential media (EMEM) containing 1% antibiotic-antimycotic, 1% HEPES and 5% fetal calf serum (FCS, Gibco), and grown to confluence at approximately 1 × 106 cells per well (9-11).
    Vero E6
    suggested: None
    Software and Algorithms
    SentencesResources
    Antigen testing: The BD Veritor (Franklin Lakes, NJ), LumiraDx (Waltham, MA), CareStart (Access Bio, Inc., Somerset, NJ), and Oscar Corona (Oscar Medicare Pvt. Ltd, New Delhi, India) SARS-CoV-2 antigen tests were performed according to the manufacturer’s instructions with the exception that 250 uL of patient sample (nasopharyngeal swab sample eluted into 3 mL of saline or viral transport medium) was pipetted into the extraction vial provided with each kit rather than direct insertion of the nasal swab into the extraction vial.
    BD Veritor
    suggested: None
    Statistics: Statistical comparisons were performed with Stata version 13.1 (Stata Corporation, College Station, TX) and/or Prism 9 for MacOS (GraphPad, San Diego, CA).
    GraphPad
    suggested: (GraphPad Prism, RRID:SCR_002798)
    Sensitivity and specificity for ROC curve analysis was determined through standard formulas in Microsoft Excel and imported into Prism for graphical representation.
    Microsoft Excel
    suggested: (Microsoft Excel, RRID:SCR_016137)

    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 design had several strengths as well as some limitations. It is known that there may be variability in results obtained from repeat sampling of the same patient, for example, due to collection technique (3, 15). We sought to eliminate this source of confounding variability by performing antigen, RT-qPCR, and viral culture testing on the same samples. Therefore, the per sample performance characteristics of each methodology could be directly compared. However, this led to the need to perform antigen testing outside of direct swab sampling testing recommendations, potentially leading to underestimation of antigen test sensitivity. Based on the dilution factor in viral transport medium, and the amount of sample used in antigen testing in our study, we estimate that antigen tests, had they been performed by directly eluting swab samples into antigen test extraction buffer, would have detected samples with approximately 17 to 18-fold lower viral loads. As such, the antigen tests would have identified samples from individuals with the lowest viral loads associated with a positive viral culture. For example, we estimate that if swab samples were tested directly without dilution in viral transport medium, LFA antigen tests would have reliably detected individuals with viral loads > ∼550,000 genome copies/mL, and the LumiraDx test would have reliably detected individuals with viral loads > ∼60,000 copies/mL (see Fig 2). It is possible though that this estimate is too high or...

    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.

  3. Version published to 10.1101/2021.12.22.21268274 on medRxiv