Comparison of anterior nares CT values in asymptomatic and symptomatic individuals diagnosed with SARS-CoV-2 in a university screening program

  1. Samantha M. Hall
  2. Lena Landaverde
  3. Christopher J. Gill
  4. Grace M. Yee
  5. Madison Sullivan
  6. Lynn Doucette-Stamm
  7. Hannah Landsberg
  8. Judy T. Platt
  9. Laura White
  10. Davidson H. Hamer
  11. Catherine M. Klapperich

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Abstract

At our university based high throughput screening program, we test all members of our community weekly using RT-qPCR. RT-qPCR cycle threshold (C T ) values are inversely proportional to the amount of viral RNA in a sample and are a proxy for viral load. We hypothesized that C T values would be higher, and thus the viral loads at the time of diagnosis would be lower, in individuals who were infected with the virus but remained asymptomatic throughout the course of the infection. We collected the N1 and N2 target gene C T values from 1633 SARS-CoV-2 positive RT-qPCR tests of individuals sampled between August 7, 2020, and March 18, 2021, at the BU Clinical Testing Laboratory. We matched this data with symptom reporting data from our clinical team. We found that asymptomatic patients had C T values significantly higher than symptomatic individuals on the day of diagnosis. Symptoms were followed by the clinical team for 10 days post the first positive test. Within the entire population, 78.1% experienced at least one symptom during surveillance by the clinical team (n = 1276/1633). Of those experiencing symptoms, the most common symptoms were nasal congestion (73%, n = 932/1276), cough (60.0%, n = 761/1276), fatigue (59.0%, n = 753/1276), and sore throat (53.1%, n = 678/1276). The least common symptoms were diarrhea (12.5%, n = 160/1276), dyspnea on exertion (DOE) (6.9%, n = 88/1276), foot or skin changes (including rash) (4.2%, n = 53/1276), and vomiting (2.1%, n = 27/1276). Presymptomatic individuals, those who were not symptomatic on the day of diagnosis but became symptomatic over the following 10 days, had C T values higher for both N1 (median = 27.1, IQR 20.2–32.9) and N2 (median = 26.6, IQR 20.1–32.8) than the symptomatic group N1 (median = 21.8, IQR 17.2–29.4) and N2 (median = 21.4, IQR 17.3–28.9) but lower than the asymptomatic group N1 (median = 29.9, IQR 23.6–35.5) and N2 (median = 30.0, IQR 23.1–35.7). This study supports the hypothesis that viral load in the anterior nares on the day of diagnosis is a measure of disease intensity at that time.

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  1. Version published to 10.1371/journal.pone.0270694
  2. ScreenIT

    SciScore for 10.1101/2022.01.12.22269139: (What is this?)

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

    Table 1: Rigor

    EthicsConsent: Ethics: This study was classified as exempt from the need for informed consent from human subjects with BU’s Charles River Campus Institutional Review Board.
    IRB: Ethics: This study was classified as exempt from the need for informed consent from human subjects with BU’s Charles River Campus Institutional Review Board.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Data analysis: Microsoft Excel and R Studio were used to analyze collected data.
    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:
    Other limitations include the absence of vaccination status as a variable in this analysis. Only 5.5% of the population with a positive test from August 8, 2020, to March 18, 2021 reported vaccinations (n=90/1633) at time of data collection. Additionally, BU did not require reporting vaccination status in the spring of 2021, which further prevented this analysis from commenting on the interaction of vaccination status with cycle threshold values or symptom experience. Sequence data were not incorporated in this study, so the authors are unable to comment regarding variants of concern (VOC), including the later-to-appear Delta and Omicron variants, or the effect of vaccination on VOCs and viral load. Sequencing initiatives begun at BU in January 2021 established that most of the local spread was still wild type virus, with the Alpha variant emerging over the January – March 2021 timeframe in the local area. In conclusion, consistent with our hypothesis, PCR signal intensity was strongly associated with symptomatology. Those who presented with symptoms at the time of diagnosis had the lowest CT values, while those who remained asymptomatic throughout had the highest CT values. Because PCR signal intensity is a measure of viral load, and by extrapolation likely a measure of infectiousness, our data support the theory that asymptomatic patients are generally less infectious than symptomatic patients.

    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

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  3. Version published to 10.1101/2022.01.12.22269139v1 on medRxiv