Factors associated with prolonged viral shedding and impact of lopinavir/ritonavir treatment in hospitalised non-critically ill patients with SARS-CoV-2 infection

  1. Dan Yan
  2. Xiao-Yan Liu
  3. Ya-nan Zhu
  4. Li Huang
  5. Bi-tang Dan
  6. Guo-jun Zhang
  7. Yong-hua Gao

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Abstract

The duration of viral shedding is central to the guidance of decisions about isolation precautions and antiviral treatment. However, studies regarding the risk factors associated with prolonged shedding of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the impact of lopinavir/ritonavir (LPV/r) treatment on viral shedding remain scarce.

Methods

Data were collected from all SARS-CoV-2 infected patients who were admitted to isolation wards and had reverse transcription PCR conversion at the No. 3 People's Hospital of Hubei province, China, between 31 January and 9 March 2020. We compared clinical characteristics and SARS-CoV-2 RNA shedding between patients initiated with LPV/r treatment and those without. Logistic regression analysis was employed to evaluate the risk factors associated with prolonged viral shedding.

Results

Of 120 patients, the median age was 52 years, 54 (45%) were male and 78 (65%) received LPV/r treatment. The median duration of SARS-CoV-2 RNA detection from symptom onset was 23 days (interquartile range 18–32 days). Older age (OR 1.03, 95% CI 1.00–1.05; p=0.03) and the lack of LPV/r treatment (OR 2.42, 95% CI 1.10–5.36; p=0.029) were independent risk factors for prolonged SARS-CoV-2 RNA shedding. Patients who initiated LPV/r treatment within 10 days from symptom onset, but not initiated from day 11 onwards, had significantly shorter viral shedding duration compared with those without LPV/r treatment (median 19 days versus 28.5 days; log-rank p<0.001).

Conclusion

Older age and the lack of LPV/r treatment were independently associated with prolonged SARS-CoV-2 RNA shedding in patients with coronavirus disease 2019 (COVID-19). Earlier administration of LPV/r treatment could shorten viral shedding duration.

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  1. ScreenIT

    SciScore for 10.1101/2020.03.22.20040832: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: The institutional review board of the NO.3 People’s Hospital of Hubei province approved the study, and patient-level informed consent were waived.
    Consent: The institutional review board of the NO.3 People’s Hospital of Hubei province approved the study, and patient-level informed consent were waived.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    All statistical analysis was performed using the SPSS version 22.0 software (IBM).
    SPSS
    suggested: (SPSS, RRID:SCR_002865)

    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:
    Our investigation has some limitations. First, owing to triage strategies, almost all patients in our hospital were categorized as general and severe COVID-19, therefore extrapolating these findings to critically ill patients need caution. Second, the estimate duration of SARS-CoV-2 RNA shedding is limited by the type of respiratory specimen, frequency of respiratory specimen collection andlack of quantitative viral RNA detection. Third, the presence of SARS-CoV-2 RNA does not necessarily indicate the production of infectious virus. Forth, we excluded fatal cases from the final analysis because all of them had detectable SARS-CoV-2 RNA until death, and time to death could not accurately reflect the duration of viral shedding, therefore the association between viral shedding and mortality could be not assessed. Finally, interpretation of our findings was limited by sample size. Further large cohort studies are still needed to define the duration of viral shedding and risk factors for prolonged viral shedding in patients with COVID-19. In summary, older age and lack of LPV/r treatment contributed to prolonged SARS-CoV-2 RNA shedding. Earlier administration of LPV/r treatment can shorten the duration of SARS-CoV-2 RNA shedding. Randomized clinical trials to determine the effectiveness of LPV/r treatment in non-critically ill patients with COVID-19 are still needed.

    Results from TrialIdentifier: We found the following clinical trial numbers in your paper:

    IdentifierStatusTitle
    NCT04307693TerminatedComparison of Lopinavir/Ritonavir or Hydroxychloroquine in P…

    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 10.1183/13993003.00799-2020
  3. Version published to 10.1101/2020.03.22.20040832v2 on medRxiv
  4. Version published to 10.1101/2020.03.22.20040832v1 on medRxiv