Invasive pulmonary aspergillosis in critically ill patients with severe COVID-19 pneumonia: Results from the prospective AspCOVID-19 study

  1. Tobias Lahmer
  2. Silja Kriescher
  3. Alexander Herner
  4. Kathrin Rothe
  5. Christoph D. Spinner
  6. Jochen Schneider
  7. Ulrich Mayer
  8. Michael Neuenhahn
  9. Dieter Hoffmann
  10. Fabian Geisler
  11. Markus Heim
  12. Gerhard Schneider
  13. Roland M. Schmid
  14. Wolfgang Huber
  15. Sebastian Rasch

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Abstract

Superinfections, including invasive pulmonary aspergillosis (IPA), are well-known complications of critically ill patients with severe viral pneumonia. Aim of this study was to evaluate the incidence, risk factors and outcome of IPA in critically ill patients with severe COVID-19 pneumonia.

Methods

We prospectively screened 32 critically ill patients with severe COVID-19 pneumonia for a time period of 28 days using a standardized study protocol for oberservation of developement of COVID-19 associated invasive pulmonary aspergillosis (CAPA). We collected laboratory, microbiological, virological and clinical parameters at defined timepoints in combination with galactomannan-antigen-detection from nondirected bronchial lavage (NBL). We used logistic regression analyses to assess if COVID-19 was independently associated with IPA and compared it with matched controls.

Findings

CAPA was diagnosed at a median of 4 days after ICU admission in 11/32 (34%) of critically ill patients with severe COVID-19 pneumonia as compared to 8% in the control cohort. In the COVID-19 cohort, mean age, APACHE II score and ICU mortality were higher in patients with CAPA than in patients without CAPA (36% versus 9.5%; p<0.001). ICU stay (21 versus 17 days; p = 0.340) and days of mechanical ventilation (20 versus 15 days; p = 0.570) were not different between both groups. In regression analysis COVID-19 and APACHE II score were independently associated with IPA.

Interpretation

CAPA is highly prevalent and associated with a high mortality rate. COVID-19 is independently associated with invasive pulmonary aspergillosis. A standardized screening and diagnostic approach as presented in our study can help to identify affected patients at an early stage.

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  1. Version published to 10.1371/journal.pone.0238825
  2. ScreenIT

    SciScore for 10.1101/2020.07.21.20158972: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementConsent: Pregnancy, age younger than 18 years, insufficient available information or lacking written informed consent were general exclusion criterias.
    IRB: The study was approved by the institutional review board
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    could be established, it was then sub-cultured on sabouraud-dextrose-agar (Oxoid™ Thermo Fisher Scientific™, Waltham, MA, United States of America) for species identification via macroscopic, microscopic and MALDI-TOF (Bruker Daltronics GmbH, Leipzig, Germany) analysis.
    Thermo Fisher Scientific™
    suggested: (Thermo Fisher Scientific, RRID:SCR_008452)

    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 study had some limitations. First, it is a single center experience and, confounding cannot be ruled out. However, this is the first prospective study evaluating a standardized screening tool in patients with severe COVID-19 pneumonie in comparison to a retrospective control cohort. Secondly, the usage of BA instead of BAL is novel and has not been evaluated in larger studies. Given the observations in our study cohort, showing that diagnosis was confirmed in several follow up examinations and by cultures, as well as the special circumstances in COVID-19 patients, we believe, that BA in mechanical ventilated patients gained through deep bronchial suction, are a suitable alternative for GM-testing. Finaly, due to the novelty of COVID-19 there is still limited information about pathophysiology and clinical characteristics particularly in critically ill patients. Therfore, further studies are needed to analyse out risk profiles for development of CAPA. In conclucion, in critically ill COVID-19 patients, Covid-19 associated invasive pulmonary aspergillosis is highly prevalent and associated with a high mortality rate. COVID-19 and a high APACHE II score are independently associated with invasive pulmonary aspergillosis. A standardized screening and diagnostic approach as presented in our study can help to identify out affected patients at an early stage.

    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

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  3. Version published to 10.1101/2020.07.21.20158972v1 on medRxiv