Evaluation of pragmatic oxygenation measurement as a proxy for Covid-19 severity

Maaike C. Swets, Steven Kerr, James Scott-Brown, Adam B. Brown, Rishi Gupta, Jonathan E. Millar, Enti Spata, Fiona McCurrach, Andrew D. Bretherick, Annemarie Docherty, David Harrison, Kathy Rowan, Neil Young, Geert H. Groeneveld, Jake Dunning, Jonathan S. Nguyen- Van-Tam, Peter Openshaw, Peter W. Horby, Ewen Harrison, Natalie Staplin, Malcolm G. Semple, Nazir Lone and J. Kenneth Baillie ()
Additional contact information
Maaike C. Swets: University of Edinburgh
Steven Kerr: University of Edinburgh
James Scott-Brown: University of Edinburgh
Adam B. Brown: University of Edinburgh
Rishi Gupta: Institute for Global Health, University College London
Jonathan E. Millar: University of Edinburgh
Enti Spata: Medical Research Council Population Health Research Unit at the University of Oxford, Nuffield Department of Population Health (NDPH)
Fiona McCurrach: Royal Infirmary Edinburgh
Andrew D. Bretherick: University of Edinburgh, Western General Hospital
Annemarie Docherty: University of Edinburgh
David Harrison: Intensive Care National Audit & Research Centre
Kathy Rowan: Intensive Care National Audit & Research Centre
Neil Young: Royal Infirmary of Edinburgh
Geert H. Groeneveld: Leiden University Medical Center, Leiden University
Jake Dunning: University of Oxford
Jonathan S. Nguyen- Van-Tam: University of Nottingham School of Medicine
Peter Openshaw: Imperial College London
Peter W. Horby: University of Oxford
Ewen Harrison: University of Edinburgh
Natalie Staplin: Medical Research Council Population Health Research Unit at the University of Oxford, Nuffield Department of Population Health (NDPH)
Malcolm G. Semple: University of Liverpool
Nazir Lone: University of Edinburgh
J. Kenneth Baillie: University of Edinburgh

Nature Communications, 2023, vol. 14, issue 1, 1-10

Abstract: Abstract Choosing optimal outcome measures maximizes statistical power, accelerates discovery and improves reliability in early-phase trials. We devised and evaluated a modification to a pragmatic measure of oxygenation function, the $$S/F$$ S / F ratio. Because of the ceiling effect in oxyhaemoglobin saturation, $$S/F$$ S / F ratio ceases to reflect pulmonary oxygenation function at high $${S}_{p}{O}_{2}$$ S p O 2 values. We found that the correlation of $$S/F$$ S / F with the reference standard ( $${P}_{a}{O}_{2}$$ P a O 2 / $${F}_{I}{O}_{2}$$ F I O 2 ratio) improves substantially when excluding $${S}_{p}{O}_{2} > 0.94$$ S p O 2 > 0.94 and refer to this measure as $$S/{F}_{94}$$ S / F 94 . Using observational data from 39,765 hospitalised COVID-19 patients, we demonstrate that $$S/{F}_{94}$$ S / F 94 is predictive of mortality, and compare the sample sizes required for trials using four different outcome measures. We show that a significant difference in outcome could be detected with the smallest sample size using $$S/{F}_{94}$$ S / F 94 . We demonstrate that $$S/{F}_{94}$$ S / F 94 is an effective intermediate outcome measure in COVID-19. It is a non-invasive measurement, representative of disease severity and provides greater statistical power.

Date: 2023
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DOI: 10.1038/s41467-023-42205-6

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