COVID-19 in-hospital mortality and mode of death in a dynamic and non-restricted tertiary care model in Germany

  1. Siegbert Rieg
  2. Maja von Cube
  3. Johannes Kalbhenn
  4. Stefan Utzolino
  5. Katharina Pernice
  6. Lena Bechet
  7. Johanna Baur
  8. Corinna N. Lang
  9. Dirk Wagner
  10. Martin Wolkewitz
  11. Winfried V. Kern
  12. Paul Biever
  13. on behalf of the COVID UKF Study Group

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Abstract

Reported mortality of hospitalised Coronavirus Disease-2019 (COVID-19) patients varies substantially, particularly in critically ill patients. So far COVID-19 in-hospital mortality and modes of death under state of the art care have not been systematically studied.

Methods

This retrospective observational monocenter cohort study was performed after implementation of a non-restricted, dynamic tertiary care model at the University Medical Center Freiburg, an experienced acute respiratory distress syndrome (ARDS) and extracorporeal membrane-oxygenation (ECMO) referral center. All hospitalised patients with PCR-confirmed SARS-CoV-2 infection were included. The primary endpoint was in-hospital mortality, secondary endpoints included major complications and modes of death. A multistate analysis and a Cox regression analysis for competing risk models were performed. Modes of death were determined by two independent reviewers.

Results

Between February 25, and May 8, 213 patients were included in the analysis. The median age was 65 years, 129 patients (61%) were male. 70 patients (33%) were admitted to the intensive care unit (ICU), of which 57 patients (81%) received mechanical ventilation and 23 patients (33%) ECMO support. Using multistate methodology, the estimated probability to die within 90 days after COVID-19 onset was 24% in the whole cohort. If the levels of care at time of study entry were accounted for, the probabilities to die were 16% if the patient was initially on a regular ward, 47% if in the intensive care unit (ICU) and 57% if mechanical ventilation was required at study entry. Age ≥65 years and male sex were predictors for in-hospital death. Predominant complications–as judged by two independent reviewers–determining modes of death were multi-organ failure, septic shock and thromboembolic and hemorrhagic complications.

Conclusion

In a dynamic care model COVID-19-related in-hospital mortality remained very high. In the absence of potent antiviral agents, strategies to alleviate or prevent the identified complications should be investigated. In this context, multistate analyses enable comparison of models-of-care and treatment strategies and allow estimation and allocation of health care resources.

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  1. Version published to 10.1371/journal.pone.0242127
  2. ScreenIT

    SciScore for 10.1101/2020.07.22.20160127: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: Ethical consideration: The study and data collection were approved by the Institutional Review Board of the University Medical Center Freiburg (348/20) and was registered in the German Clinical Trials Register (identifier DRKS00021775).
    Consent: The Institutional Review Board of the University Medical Center Freiburg considered the collection of routine data as evaluation of service and waived the need for written informed consent.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    No key resources detected.

    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 has limitations, primarily those inherent to its retrospective observational design. It is a monocenter study, which may limit generalisability. Yet the monocentric design may be considered a prerequisite to study treatment results in a specific care model at an experienced ARDS center. The limited number of patients precluded an analysis of specific treatment strategies, both in terms of antiviral or anti-inflammatory agents and time-sensitive supportive strategies. While the primary endpoint of in-hospital death is reliably determined retrospectively, uncertainties remain in evaluating the mode of death. We tried to minimize this uncertainty by performing individual case review by two independent experienced physicians and explicitly avoiding causal assumptions.

    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 10.1101/2020.07.22.20160127v1 on medRxiv