Correlation of Population SARS-CoV-2 Cycle Threshold Values to Local Disease Dynamics: Exploratory Observational Study

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Abstract

Despite the limitations in the use of cycle threshold (CT) values for individual patient care, population distributions of CT values may be useful indicators of local outbreaks.

Objective

We aimed to conduct an exploratory analysis of potential correlations between the population distribution of cycle threshold (CT) values and COVID-19 dynamics, which were operationalized as percent positivity, transmission rate (Rt), and COVID-19 hospitalization count.

Methods

In total, 148,410 specimens collected between September 15, 2020, and January 11, 2021, from the greater El Paso area were processed in the Dascena COVID-19 Laboratory. The daily median CT value, daily Rt, daily count of COVID-19 hospitalizations, daily change in percent positivity, and rolling averages of these features were plotted over time. Two-way scatterplots and linear regression were used to evaluate possible associations between daily median CT values and outbreak measures. Cross-correlation plots were used to determine whether a time delay existed between changes in daily median CT values and measures of community disease dynamics.

Results

Daily median CT values negatively correlated with the daily Rt values (P<.001), the daily COVID-19 hospitalization counts (with a 33-day time delay; P<.001), and the daily changes in percent positivity among testing samples (P<.001). Despite visual trends suggesting time delays in the plots for median CT values and outbreak measures, a statistically significant delay was only detected between changes in median CT values and COVID-19 hospitalization counts (P<.001).

Conclusions

This study adds to the literature by analyzing samples collected from an entire geographical area and contextualizing the results with other research investigating population CT values.

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  1. SciScore for 10.1101/2021.02.16.21251844: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: The Pearl Independent Institutional Review Board (IRB) approved this study (IRB Protocol 21-DASC-127).
    RandomizationAs the purpose of the present analysis was to investigate how the trough of daily median CT correlated with the peak of the other signals, to aid visualization the following modifications were made: (1) for each signal, the z-score was used instead of the absolute value; (2) the negative value of the z-score of daily median CT value was used to ensure a positive peak in the cross correlation plots; (3) 20% of positive samples were randomly sampled five times each day to estimate the variation in the cross-correlation between daily median CT value and epidemiological signals.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    The algorithm is a Python script based on a Bayesian Estimation Model developed by Bettencourt & Ribeiro (28), with slight modification to introduce gaussian noise to the prediction.
    Python
    suggested: (IPython, RRID:SCR_001658)
    Statistical Analysis: All analyses were conducted in Python (31) using the following packages: pandas, matplotlib, plotly, scipy and statsmodels.
    matplotlib
    suggested: (MatPlotLib, RRID:SCR_008624)
    scipy
    suggested: (SciPy, RRID:SCR_008058)

    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:
    Limitations: While the study sample was large, other variables and forms of bias (e.g., sampling bias), may have influenced the results. Indeed, differences in the comprehensiveness of the El Paso dataset versus the supplementary site datasets-or in, other words, the relative proportion of tests conducted by the Dascena laboratory versus other testing providers-may have contributed to skew in the supplementary samples. Future directions for research on population CT values may therefore include analyzing whether significant differences in results can be detected in different sub-samples of tested populations, and evaluating methods to collate CT data across testing providers in a given geographic area. No data on symptomatology was associated with samples at the time of collection, such that these data do not enable a distinction between samples collected as part of clinical evaluation of symptoms consistent with COVID-19, or for other reasons (e.g., clearance for work or travel). Prior research assessing population distribution of CT values in relation to community outbreaks has explicitly used surveillance samples (23,24). The variability in the observed correlations between median CT and outbreak measures in El Paso versus other testing locations may reflect, in part, variability in the proportion of symptomatically indicated versus non-symptomatically indicated tests in a given location. However, other differences between the testing site populations may also have contrib...

    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.