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

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 SpO₂, 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 (SpO₂) fell to 91% or less. A statistically significant correlation was found between SpO₂ 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.

Keywords: COVID-19; SARS-CoV2; early intervention; mortality; oxygen; rationing; target oxygen saturation; treatment.

Figure 1

Study protocol flowchart. Using the WHO situation report countries with case numbers over 20,000 were selected. These countries were subjected to analysis via three different, independent investigators for the ascertainment of nationally recommended target oxygen saturations.

Figure 2

Scatter graph of national target oxygen saturations vs. national case fatality rate with best fit linear line (n = 26). SpO₂–oxygen saturations.

Figure 3

Scatter graphs with best-fit line for primary measure and confounders vs. CFR (N = 26). CFR is along the vertical axis in each and measured as percentage ratio. (A) Comparison of national CFR vs. nationally recommended target SpO2 (%) in COVID-19. (B) CFR vs. burden of cases measured by total number of cases per million inhabitants. (C) CFR vs. Testing Rate measured by total number of tests undertaken per thousand inhabitants (tests/thousand). (D) CFR vs. the overall positivity ratio (%), measured as the percentage ratio of positive tests to total tests. CFR, case fatality rate; SpO₂, oxygen saturations. CFR, case fatality rate; SpO₂, oxygen saturations.