Antigen-Based Testing but Not Real-Time Polymerase Chain Reaction Correlates With Severe Acute Respiratory Syndrome Coronavirus 2 Viral Culture

  1. Andrew Pekosz
  2. Valentin Parvu
  3. Maggie Li
  4. Jeffrey C Andrews
  5. Yukari C Manabe
  6. Salma Kodsi
  7. Devin S Gary
  8. Celine Roger-Dalbert
  9. Jeffry Leitch
  10. Charles K Cooper

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Abstract

Background

Individuals can test positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by molecular assays following the resolution of their clinical disease. Recent studies indicate that SARS-CoV-2 antigen–based tests are likely to be positive early in the disease course, when there is an increased likelihood of high levels of infectious virus.

Methods

Upper respiratory specimens from 251 participants with coronavirus disease 2019 symptoms (≤7 days from symptom onset) were prospectively collected and tested with a lateral flow antigen test and a real-time polymerase chain reaction (rt-PCR) assay for detection of SARS-CoV-2. Specimens from a subset of the study specimens were utilized to determine the presence of infectious virus in the VeroE6TMPRSS2 cell culture model.

Results

The antigen test demonstrated a higher positive predictive value (90%) than rt-PCR (70%) when compared to culture-positive results. The positive percentage agreement for detection of infectious virus for the antigen test was similar to rt-PCR when compared to culture results.

Conclusions

The correlation between SARS-CoV-2 antigen and SARS-CoV-2 culture positivity represents a significant advancement in determining the risk for potential transmissibility beyond that which can be achieved by detection of SARS-CoV-2 genomic RNA. SARS-CoV-2 antigen testing can facilitate low-cost, scalable, and rapid time-to-result, while providing good risk determination of those who are likely harboring infectious virus, compared to rt-PCR.

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  3. ScreenIT

    SciScore for 10.1101/2020.10.02.20205708: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementConsent: No study-related procedures were performed without an informed consent process or signature of a consent form.
    RandomizationThe 76 specimens consisted of all 38 RT-PCR assay positive specimens, and 38, randomly selected RT-PCR assay negative specimens from the parent study.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    All analyses were performed using the R software system and the ggplot2 R package.
    ggplot2
    suggested: (ggplot2, RRID:SCR_014601)

    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 study had limitations. It only included specimens from patients within seven days of symptom onset. Several studies have demonstrated an inability to culture SARS-CoV-2 beyond day eight, despite ongoing RT-PCR positivity.1,3,5 Serial sampling of COVID-19 patients is needed to determine if there is a propensity to have viral antigen test positive results after a negative result, as can sometimes be seen with RT-PCR tests. Results from this study likely underestimate the difference in specificity between RT-PCR and antigen testing that would be expected in a set that included specimens collected at later times post symptom onset. In this study, while three subjects were antigen test false positives versus SARS-CoV-2 TMPRSS2 culture, as many as ten subjects were RT-PCR false positives versus culture (viral RNA loads ranging from 2.6 to 5.4 log10 copies/mL). Although the sample size was adequate in this study, the confidence intervals in the probit model were too wide to establish a definitive viral load cut-off. To improve the precision associated with the point estimates, either a larger study or a meta-analysis, involving multiple studies, would be required. Also, there are limitations associated with the use of culture positivity or viral RNA load as a surrogate for infectiousness or transmissibility that require further investigation. Finally, it is unclear how well the results here will extrapolate to the other antigen tests due to variability in limit of detection 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.

    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.

  4. Version published to 10.1093/cid/ciaa1706
  5. Version published to 10.1101/2020.10.02.20205708v1 on medRxiv