SARS‐CoV‐2 RNAemia with a higher nasopharyngeal viral load is strongly associated with disease severity and mortality in patients with COVID‐19

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Abstract

This study aimed to determine the frequency of SARS‐CoV‐2 RNA in serum and its association with the clinical severity of COVID‐19. This retrospective cohort study performed at Toyama University Hospital included consecutive patients with confirmed COVID‐19. The prevalence of SARS‐CoV‐2 RNAemia and the strength of its association with clinical severity variables were examined. Fifty‐six patients were included in this study. RNAemia was detected in 19.6% (11/56) patients on admission, and subsequently in 1.0% (1/25), 50.0% (6/12), and 100.0% (4/4) moderate, severe, and critically ill patients, respectively. Patients with RNAemia required more frequent oxygen supplementation (90.0% vs. 13.3%), ICU admission (81.8% vs. 6.7%), and invasive mechanical ventilation (27.3% vs. 0.0%). Among patients with RNAemia, the median viral loads of nasopharyngeal (NP) swabs that were collected around the same time as the serum sample were significantly higher in critically ill (5.4 log 10 copies/μl; interquartile range [IQR]: 4.2–6.3) than in moderate‐severe cases (2.6 log 10 copies/μl; [IQR: 1.1–4.5]; p  = 0.030) and were significantly higher in nonsurvivors (6.2 log 10 copies/μl [IQR: 6.0–6.5]) than in survivors (3.9 log 10 copies/μl [IQR: 1.6–4.6]; p  = 0.045). This study demonstrated a relatively high proportion of SARS‐CoV‐2 RNAemia and an association between RNAemia and clinical severity. Moreover, among the patients with RNAemia, the viral loads of NP swabs were correlated with disease severity and mortality, suggesting the potential utility of combining serum testing with NP tests as a prognostic indicator for COVID‐19, with higher quality than each separate test.

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  1. SciScore for 10.1101/2020.12.17.20248388: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: Ethics approval: This study was performed in accordance with the Declaration of Helsinki and was approved by the Ethical Review Board of the University of Toyama (approval No.: R2019167).
    Consent: Written informed consent was obtained from all patients.
    Randomizationnot detected.
    Blindingnot detected.
    Power AnalysisThe sample size was based on a convenience set of all available clinical samples without formal power calculation
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Data were analyzed using JMP Pro version 14.2.0 software (SAS Institute Inc.
    SAS Institute
    suggested: (Statistical Analysis System, RRID:SCR_008567)

    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 study has several limitations inherent to its small sample size, retrospective design, and potential for confounding the detection of SARS-CoV-2 RNA from the serum, NP viral load, and clinical conditions that cannot be excluded. In addition, we did not conduct multivariate and age-adjusted analyses owing to the strong multicollinearity between variables and the small sample size. Longitudinal analyses were also not performed because viral load dynamics could be modified by the received treatment, including combinations of antivirals and antibiotics during hospitalization.

    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.