A simple algorithm based on initial Ct values predicts the duration to SARS-CoV-2 negativity and allows more efficient test-to-release and return-to-work schedules

  1. Olympia E. Anastasiou
  2. Vu Thuy Khanh Le-Trilling
  3. Mirko Trilling

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Abstract

Especially during global pandemics but also in the context of epidemic waves, the capacity for diagnostic qRT-PCRs rapidly becomes a limiting factor. Furthermore, excessive testing incurs high costs and can result in an overstrained work force in diagnostics departments. Obviously, people aim to shorten their isolation periods, hospitals need to discharge convalescent people, and re-employ staff members after infection. The aim of the study was to optimize retesting regimens for test-to-release from isolation and return-to-work applications. For this purpose, we investigated the association between Ct values at the first diagnosis of SARS-CoV-2 infection and the period until test negativity was reached, or at least until the Ct value exceeded 30, which is considered to indicate the transition to a non-infectious state. We included results from the testing of respiratory material samples for the detection of SARS-CoV-2 RNA, tested from 01 March 2020 to 31 January 2022.

Lower initial Ct values were associated with longer periods of SARS-CoV-2 RNA positivity. Starting with Ct values of <20, 20-25, 25-30, 30-35, and >35, it took median intervals of 20 (interval: 14-25), 16 (interval: 10-21), 12 (interval: 7-16), 7 (interval: 5-14), and 5 (interval: 2-7) days, respectively, until the person tested negative. Accordingly, a Ct threshold of 30 was surpassed after 13 (interval: 8-19), 9 (interval: 6-14), 7 (interval: 6-11), 6 (interval: 4-10), and 3 (interval: 1-6) days, respectively, in individuals with aforementioned start Ct values. Furthermore, the time to negativity was longer for adults versus children, wild-type SARS-CoV-2 variant versus other variants of concern, and in patients who were treated in the intensive care units.

Based on these data, we propose an adjusted retesting strategy according to the initial Ct value in order to optimize available PCR resources.

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    SciScore for 10.1101/2022.04.04.22273384: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: The ethics committee of the medical faculty of the University of Duisburg-Essen approved the analysis of data for the improvement of diagnostic procedures (20-9512-BO).
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    SARS-CoV-2 Assay (Abbott, Wiesbaden, Germany), Abbott RealTime SARS-CoV-2 assay (Abbott, Wiesbaden, Germany)
    Abbott
    suggested: (Abbott, RRID:SCR_010477)
    3, SPSS Inc., Chicago, IL, USA) and GraphPad Prism 6.0 (GraphPad, CA, USA).
    SPSS
    suggested: (SPSS, RRID:SCR_002865)
    GraphPad
    suggested: (GraphPad Prism, RRID:SCR_002798)

    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 analysis has some limitations. We have no data on patient symptoms (including severity and time of onset) and some of the cases may have been diagnosed before as SARS-CoV-2 positive, prior to admittance. However, our data provide a valuable insight on the dynamic of viral shedding of SARS-CoV-2. To date, more than 5 billion COVID-19 tests have been performed worldwide since the beginning of the pandemic 1. The gold standard for SARS-CoV-2 diagnostics is the real-time PCR 11. It requires specialized equipment and personnel, is expensive and due to rapid increase in its use shortages in reagents have been observed. In an effort to reduce PCR testing and thus preserve resources, rapid SARS-CoV-2 tests have been recommended as an alternative in many but not all cases 2,5. Notwithstanding the concerted effort to reduce PCR testing, it has been our experience that testing in ours and other hospitals is more rigorous and less uniform in different departments than official national recommendations (see Introduction). A negative PCR result is more often than not necessary to release a patient from isolation, health care personnel can resume their duties with a negative or low positive (Ct>30) PCR result. Adapting the testing PCR strategy according to previous Ct values could be a way to save laboratory and personnel resources. It could be also used to manage hospital resources (personnel, bed capacity) more efficiently.

    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.

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  2. Version published to 10.1101/2022.04.04.22273384 on medRxiv