Ventilator-associated pneumonia in critically ill patients with COVID-19

  1. Mailis Maes
  2. Ellen Higginson
  3. Joana Pereira-Dias
  4. Martin D. Curran
  5. Surendra Parmar
  6. Fahad Khokhar
  7. Delphine Cuchet-Lourenço
  8. Janine Lux
  9. Sapna Sharma-Hajela
  10. Benjamin Ravenhill
  11. Islam Hamed
  12. Laura Heales
  13. Razeen Mahroof
  14. Amelia Soderholm
  15. Sally Forrest
  16. Sushmita Sridhar
  17. Nicholas M. Brown
  18. Stephen Baker
  19. Vilas Navapurkar
  20. Gordon Dougan
  21. Josefin Bartholdson Scott
  22. Andrew Conway Morris

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Abstract

Background

Pandemic COVID-19 caused by the coronavirus SARS-CoV-2 has a high incidence of patients with severe acute respiratory syndrome (SARS). Many of these patients require admission to an intensive care unit (ICU) for invasive ventilation and are at significant risk of developing a secondary, ventilator-associated pneumonia (VAP).

Objectives

To study the incidence of VAP and bacterial lung microbiome composition of ventilated COVID-19 and non-COVID-19 patients.

Methods

In this retrospective observational study, we compared the incidence of VAP and secondary infections using a combination of microbial culture and a TaqMan multi-pathogen array. In addition, we determined the lung microbiome composition using 16S RNA analysis in a subset of samples. The study involved 81 COVID-19 and 144 non-COVID-19 patients receiving invasive ventilation in a single University teaching hospital between March 15th 2020 and August 30th 2020.

Results

COVID-19 patients were significantly more likely to develop VAP than patients without COVID (Cox proportional hazard ratio 2.01 95% CI 1.14–3.54, p  = 0.0015) with an incidence density of 28/1000 ventilator days versus 13/1000 for patients without COVID ( p  = 0.009). Although the distribution of organisms causing VAP was similar between the two groups, and the pulmonary microbiome was similar, we identified 3 cases of invasive aspergillosis amongst the patients with COVID-19 but none in the non-COVID-19 cohort. Herpesvirade activation was also numerically more frequent amongst patients with COVID-19.

Conclusion

COVID-19 is associated with an increased risk of VAP, which is not fully explained by the prolonged duration of ventilation. The pulmonary dysbiosis caused by COVID-19, and the causative organisms of secondary pneumonia observed are similar to that seen in critically ill patients ventilated for other reasons.

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  1. Version published to 10.1186/s13054-021-03460-5
  2. ScreenIT

    SciScore for 10.1101/2020.06.26.20139873: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    The resulting fastq files were de-multiplexed with guppy_barcoder v3.6.0 using the -- require_barcodes_both_ends and --trim_barcodes flags.
    guppy_barcoder
    suggested: None
    Porechop v0.2.4 (https://github.com/rrwick/Porechop) was used to trim adapter and barcode sequences and Nanofilt v2.6.0 (De Coster, et. al., 2018) was used to filter the reads by length, 1,400 – 1,600 bps and a quality score of 10.
    Porechop
    suggested: (Porechop, RRID:SCR_016967)
    Nanofilt
    suggested: (NanoFilt, RRID:SCR_016966)
    % OTUs 16S database using Kraken2 [19].
    Kraken2
    suggested: None

    Results from OddPub: Thank you for sharing your data.

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    We acknowledge the sample size limitations with our observations and suggest larger studies from distinct geographic locations may help fully understand the risk of developing secondary bacterial infections in patients with severe COVID-19.

    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 10.1101/2020.06.26.20139873v1 on medRxiv
  4. Version published to 10.1101/2020.06.26.20139873v2 on medRxiv