Coronavirus Disease 2019 as Cause of Viral Sepsis: A Systematic Review and Meta-Analysis*

  1. Eleni Karakike
  2. Evangelos J. Giamarellos-Bourboulis
  3. Miltiades Kyprianou
  4. Carolin Fleischmann-Struzek
  5. Mathias W. Pletz
  6. Mihai G. Netea
  7. Konrad Reinhart
  8. Evdoxia Kyriazopoulou

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Abstract

Coronavirus disease 2019 is a heterogeneous disease most frequently causing respiratory tract infection, which can induce respiratory failure and multiple organ dysfunction syndrome in its severe forms. The prevalence of coronavirus disease 2019–related sepsis is still unclear; we aimed to describe this in a systematic review.

Data Sources:

MEDLINE (PubMed), Cochrane, and Google Scholar databases were searched based on a prespecified protocol (International Prospective Register for Systematic Reviews: CRD42020202018).

Study Selection:

Studies reporting on patients with confirmed coronavirus disease 2019 diagnosed with sepsis according to sepsis-3 or according to the presence of infection-related organ dysfunctions necessitating organ support/replacement were included in the analysis. The primary end point was prevalence of coronavirus disease 2019–related sepsis among adults hospitalized in the ICU and the general ward. Among secondary end points were the need for ICU admission among patients initially hospitalized in the general ward and the prevalence of new onset of organ dysfunction in the ICU. Outcomes were expressed as proportions with respective 95% CI.

Data Extraction:

Two reviewers independently screened and reviewed existing literature and assessed study quality with the Newcastle-Ottawa Scale and the Methodological index for nonrandomized studies.

Data Synthesis:

Of 3,825 articles, 151 were analyzed, only five of which directly reported sepsis prevalence. Noting the high heterogeneity observed, coronavirus disease 2019–related sepsis prevalence was 77.9% (95% CI, 75.9–79.8; I 2 = 91%; 57 studies) in the ICU, and 33.3% (95% CI, 30.3–36.4; I 2 = 99%; 86 studies) in the general ward. ICU admission was required for 17.7% (95% CI, 12.9–23.6; I 2 = 100%) of ward patients. Acute respiratory distress syndrome was the most common organ dysfunction in the ICU (87.5%; 95% CI, 83.3–90.7; I 2 = 98%).

CONCLUSIONS:

The majority of coronavirus disease 2019 patients hospitalized in the ICU meet Sepsis-3 criteria and present infection-associated organ dysfunction. The medical and scientific community should be aware and systematically report viral sepsis for prognostic and treatment implications.

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  1. Version published to 10.1097/ccm.0000000000005195
  2. ScreenIT

    SciScore for 10.1101/2020.12.02.20242354: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    RandomizationInclusion criteria comprised randomized and non-randomized clinical trials and observational studies reporting on the proportion of patients diagnosed with confirmed COVID-19, who were diagnosed with sepsis, had infection-related organ dysfunctions, or received organ replacement therapy (dialysis, mechanical ventilation, extracorporeal membrane oxygenation [ECMO], liver replacement therapy).
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    The search of the peer-reviewed medical literature was conducted across MEDLINE (PubMed), Cochrane and Google Scholar databases using the following terms: “COVID-19” or “SARS-CoV-2” and “sepsis”, “organ failure”, “organ dysfunction”.
    MEDLINE
    suggested: (MEDLINE, RRID:SCR_002185)
    Cochrane
    suggested: (Cochrane Library, RRID:SCR_013000)
    Google Scholar
    suggested: (Google Scholar, RRID:SCR_008878)
    Some results were validated in the Review Manager (RevMan, The Cochrane Collaboration) Version 5.4.
    RevMan
    suggested: (RevMan, RRID:SCR_003581)
    Cochrane Collaboration
    suggested: None

    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: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    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.

  3. Version published to 10.1101/2020.12.02.20242354 on medRxiv