Discontinuation of isolation for persons with COVID-19: Is 10 days really safe?

  1. Alvina Clara Felix
  2. Anderson V de Paula
  3. Andreia Cristina Ribeiro
  4. Francini Camila da Silva
  5. Marta Inemami
  6. Angela A Costa
  7. Cibele Odete D Leal
  8. Walter M Figueiredo
  9. Claudio Sérgio Pannuti
  10. Camila Malta Romano

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Abstract

Background

The detection of SARS-CoV-2 RNA by real-time polymerase chain reaction (PCR) in respiratory samples from COVID-19 patients is not a direct indication of the presence of viable viruses. The isolation of SARS-CoV-2 in cell culture system however, can acts as surrogate marker of infectiousness. Cell culture based studies performed mostly with hospitalized and moderate/severe COVID-19 claims that no replication competent virus is found after 9 days of the symptoms onset in respiratory samples. Therefore, it is now recommended 10 days isolation before patient discharge.

Methods

We cell-cultured 29 SARS-COV-2 RT-PCR positive respiratory samples at the 10 th day after the illness in Vero E6 cells. After two passages, cytopathic effect and cycle threshold (CT) lower than the obtained in the original sample were used to determine positivity.

Findings

We found viable particles in (7/29) 24% of samples tested. The positivity in cell culture was strongly associated (p<0.0001) to the low cycle thresholds in clinical samples (Ct <21).

Conclusion

This data adds important knowledge to the current protocols for de-isolation of patients with non-hospitalized mild COVID-19.

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  1. ScreenIT

    SciScore for 10.1101/2021.01.29.21250753: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: The project was approved by the Ethical committee from the Medical School of the University of Sao Paulo (CAPPESQ # 4.235.245).
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Experimental Models: Cell Lines
    SentencesResources
    From a subset of the positive ones, 0.2ml of the raw samples were put in Vero E6 cells for isolation.
    Vero E6
    suggested: RRID:CVCL_XD71)
    Software and Algorithms
    SentencesResources
    Statistical analysis was performed with GraphPad Prism version 7.0.
    GraphPad Prism
    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:
    Limitations of this study include the limited volume of clinical sample that precluded the viral isolation of all positive samples in D10 and the absence of successive clinical samples that would allow us to determine how long the individuals were still infectious. In summary, available data on SARS-COV-2 culture along the disease are scarce, but indicated so far that persons with mild or moderate COVID-19 remain infectious no longer than 9 days after the symptom onset. Here we present for the first time evidences that individuals with CT values <21 in clinical samples at the 10th day present replication competent viruses at this time. It is crucial to have in mind that we are not fully aware about the sensitivity of the viral culture to recover SARS-COV-2 viable particles, which means that negative viral cultures do not necessarily implies that no infectious particle is present at all. Further studies are needed to determine if viable viruses can occur, as well as in what proportion, between the 10th and 14th days after disease onset. Transmission control strategies focused solely on the presence/absence of symptoms and qualitative PCR results to determine isolation time may be not sufficient to prevent SARS-COV-2 transmission. This work has important implications on the public health and epidemiological surveillance focused on mitigate the SARS-COV-2 transmission chain.

    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.

  2. Version published to 10.1101/2021.01.29.21250753v1 on medRxiv