Oxygen and Mortality in COVID-19 Pneumonia: A Comparative Analysis of Supplemental Oxygen Policies and Health Outcomes Across 26 Countries

  1. Fatma Mansab
  2. Harry Donnelly
  3. Albrecht Kussner
  4. James Neil
  5. Sohail Bhatti
  6. Daniel K. Goyal

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Abstract

Introduction: Hypoxia is the main cause of morbidity and mortality in COVID-19. During the COVID-19 pandemic, some countries have reduced access to supplemental oxygen, whereas other nations have maintained and even improved access to supplemental oxygen. We examined whether variation in the nationally determined oxygen guidelines had any association with national mortality rates in COVID-19.

Methods: Three independent investigators searched for, identified, and extracted the nationally recommended target oxygen levels for the commencement of oxygen in COVID-19 pneumonia from the 29 worst affected countries. Mortality estimates were calculated from three independent sources. We then applied both parametric (Pearson's R) and non-parametric (Kendall's Tau B) tests of bivariate association to determine the relationship between case fatality rate (CFR) and target SpO 2 , and also between potential confounders and CFR.

Results: Of the 26 nations included, 15 had employed conservative oxygen strategies to manage COVID-19 pneumonia. Of them, Belgium, France, USA, Canada, China, Germany, Mexico, Spain, Sweden, and the UK guidelines advised commencing oxygen when oxygen saturations (SpO 2 ) fell to 91% or less. A statistically significant correlation was found between SpO 2 and CFR both parametrically ( R = −0.53, P < 0.01) and non-parametrically (−0.474, P < 0.01).

Conclusion: Our study highlights the disparity in oxygen provision for COVID-19 patients between the nations analysed. In those nations that pursued a conservative oxygen strategy, there was an association with higher national mortality rates. We discuss the potential reasons for such an association.

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  1. Version published to 10.3389/fpubh.2021.580585
  2. ScreenIT

    SciScore for 10.1101/2020.07.03.20145763: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    Randomizationnot detected.
    BlindingTwo investigators were blinded as to the reason for the study.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    We followed the advice for global reporting on health estimates as per the GATHER statement[7].
    GATHER
    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: We detected the following sentences addressing limitations in the study:
    Resource limitations: For some nations there was a resource limitation issue, or at least a fear of resource limitation, with secondary implementation of conservative oxygen strategies. For example, the UK directive to ration oxygen supply in April 2020 reduced the normal national target for the commencement of oxygen from SpO2 of 94% to a new value of 91%. The reason for rationing was related to the surge of infections and subsequent concern over the supply of oxygen[18]. If such practises are common in other nations, the relationship between national guidelines’ SpO2 and national CFR identified here may be a representation of the demands on healthcare during a surge of COVID-19 cases. There are a number of reasons why mortality increases during a surge of infections. Patients are less likely to attend hospital or seek medical care, either for fear of contracting COVID-19 or over-burdening their health service[19]. Triage systems during a surge can be set with high thresholds for onward referrals[20]. Another mortality factor is a potential lack of resources both staff and consumables. The overall delay to treatment that ensues prevents early correction of hypoxia, implementation of VTE (venous thromboembolism) prophylaxis, readjustment of medications (e.g. nephrotoxics) and the detection of secondary bacterial infection, and thus a likely increased mortality[21] So then, the association between target SpO2 and CFR identified here may be more related to target SpO2 being an ...

    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 10.1101/2020.07.03.20145763v1 on medRxiv