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

Maaike C.  Swets; Steven Kerr; James Scott-Brown; Adam Brown; Rishi K Gupta; Jonathan Millar; Enti  Spata; Fiona  McCurrach; Andrew D Bretherick; Annemarie B Docherty; David Harrison; Kathy Rowan; Neil Young; Geert H  Groeneveld; Jake Dunning; Jonathan S. Nguyen-Van-Tam; Peter Openshaw; Peter Horby; Ewen M Harrison; Natalie Staplin; Malcolm G Semple; Nazir I Lone; J Kenneth Baillie

doi:10.1038/s41467-023-42205-6

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

Maaike C. Swets, Steven Kerr, James Scott-Brown, Adam Brown, Rishi K Gupta, Jonathan Millar, Enti Spata, Fiona McCurrach, Andrew D Bretherick, Annemarie B Docherty, David Harrison, Kathy Rowan, Neil Young, Geert H Groeneveld, Jake Dunning, Jonathan S. Nguyen-Van-Tam, Peter Openshaw, Peter Horby, Ewen M Harrison, Natalie StaplinMalcolm G Semple, Nazir I Lone, J Kenneth Baillie

Research output: Contribution to journal › Article › peer-review

Abstract / Description of output

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 ratio.
Because of the ceiling effect in oxyhaemoglobin saturation, 𝑆/𝐹 ratio ceases to reflect pulmonary oxygenation function at high 𝑆𝑝𝑂2 values. We found that the correlation of 𝑆/𝐹 with the reference standard (𝑃𝑎𝑂2/𝐹𝐼𝑂2 ratio) improves substantially when excluding 𝑆𝑝𝑂2 > 0.94 and refer to this measure as 𝑆/𝐹94.
Using observational data from 39,765 hospitalised COVID-19 patients, we demonstrate that 𝑆/𝐹94 isn 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/𝐹94.
We demonstrate that 𝑆/𝐹94 is an effective intermediate outcome measure in COVID-19. It is a noninvasive measurement, representative of disease severity and provides greater statistical power.

Original language	English
Article number	7374
Pages (from-to)	1-10
Number of pages	10
Journal	Nature Communications
Volume	14
Issue number	1
Early online date	15 Nov 2023
DOIs	https://doi.org/10.1038/s41467-023-42205-6
Publication status	Published - 15 Nov 2023

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10.1038/s41467-023-42205-6

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s41467-023-42205-6Final published version, 1.85 MBLicence: Creative Commons: Attribution (CC-BY)

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2 Finished

Translational genomics in critical care medicine
Baillie, K.
UK-based charities
1/12/21 → 30/11/26
Project: Research
ISP 1 2017/22 Blueprints for Healthy Animals
Watson, M.
BBSRC
1/04/17 → 31/03/22
Project: Research
ISP 3 2017/22 Improving Animal Health and Welfare
Meddle, S.
BBSRC
1/04/17 → 31/03/22
Project: Research

Cite this

Swets, M. C., Kerr, S., Scott-Brown, J., Brown, A., Gupta, R. K., Millar, J., Spata, E., McCurrach, F., Bretherick, A. D., Docherty, A. B., Harrison, D., Rowan, K., Young, N., Groeneveld, G. H., Dunning, J., Nguyen-Van-Tam, J. S., Openshaw, P., Horby, P., Harrison, E. M., ... Baillie, J. K. (2023). Evaluation of pragmatic oxygenation measurement as a proxy for Covid-19 severity. Nature Communications, 14(1), 1-10. Article 7374. https://doi.org/10.1038/s41467-023-42205-6

@article{50b2980ff4b048c9a39ed3b3f9d12cab,

title = "Evaluation of pragmatic oxygenation measurement as a proxy for Covid-19 severity",

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 푆/퐹 ratio.Because of the ceiling effect in oxyhaemoglobin saturation, 푆/퐹 ratio ceases to reflect pulmonary oxygenation function at high 푆푝푂2 values. We found that the correlation of 푆/퐹 with the reference standard (푃푎푂2/퐹퐼푂2 ratio) improves substantially when excluding 푆푝푂2 > 0.94 and refer to this measure as 푆/퐹94.Using observational data from 39,765 hospitalised COVID-19 patients, we demonstrate that 푆/퐹94 isn 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 samplesize using 푆/퐹94.We demonstrate that 푆/퐹94 is an effective intermediate outcome measure in COVID-19. It is a noninvasive measurement, representative of disease severity and provides greater statistical power.",

author = "Swets, {Maaike C.} and Steven Kerr and James Scott-Brown and Adam Brown and Gupta, {Rishi K} and Jonathan Millar and Enti Spata and Fiona McCurrach and Bretherick, {Andrew D} and Docherty, {Annemarie B} and David Harrison and Kathy Rowan and Neil Young and Groeneveld, {Geert H} and Jake Dunning and Nguyen-Van-Tam, {Jonathan S.} and Peter Openshaw and Peter Horby and Harrison, {Ewen M} and Natalie Staplin and Semple, {Malcolm G} and Lone, {Nazir I} and Baillie, {J Kenneth}",

note = "Funding Information: This work uses data provided by patients and collected by the NHS as part of their care and support. We are extremely grateful for the front-line NHS clinical and research staff and volunteer medical students who collected this data in challenging circumstances, and the generosity of the participants and their families for their individual contributions in these difficult times. We also acknowledge the support of Jeremy J Farrar (Wellcome Trust) and Nahoko Shindo (WHO). For the purpose of open access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. JKB gratefully acknowledges funding support from a Wellcome Trust Senior Research Fellowship (223164/Z/21/Z), UKRI grants MC_PC_20004, MC_PC_19025, MC_PC_1905, MRNO2995X/1, and MC_PC_20029, Sepsis Research (Fiona Elizabeth Agnew Trust), a BBSRC Institute Strategic Programme Grant to the Roslin Institute (BB/P013732/1, BB/P013759/1), and the UK Intensive Care Society. ISARIC4C work was supported by the National Institute for Health Research (NIHR), the Medical Research Council [MC_PC_19059] and by the NIHR Health Protection Research Unit (HPRU) in Emerging and Zoonotic Infections at University of Liverpool in partnership with Public Health England (PHE), in collaboration with Liverpool School of Tropical Medicine and the University of Oxford [200907], NIHR HPRU in Respiratory Infections at Imperial College London with PHE [200927], Wellcome Trust and Department for International Development [215091/Z/18/Z], and the Bill and Melinda Gates Foundation [OPP1209135], and Liverpool Experimental Cancer Medicine Centre (C18616/A25153), NIHR Biomedical Research Centre at Imperial College London [IS-BRC-1215-20013], EU Platform for European Preparedness Against (Re-) emerging Epidemics (PREPARE) [FP7 project 602525] and NIHR Clinical Research Network for providing infrastructure support for this research. Publisher Copyright: {\textcopyright} 2023, The Author(s).",

year = "2023",

month = nov,

day = "15",

doi = "10.1038/s41467-023-42205-6",

language = "English",

volume = "14",

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journal = "Nature Communications",

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Swets, MC, Kerr, S, Scott-Brown, J, Brown, A, Gupta, RK, Millar, J, Spata, E, McCurrach, F, Bretherick, AD , Docherty, AB, Harrison, D, Rowan, K, Young, N, Groeneveld, GH, Dunning, J, Nguyen-Van-Tam, JS, Openshaw, P, Horby, P, Harrison, EM, Staplin, N, Semple, MG, Lone, NI & Baillie, JK 2023, 'Evaluation of pragmatic oxygenation measurement as a proxy for Covid-19 severity', Nature Communications, vol. 14, no. 1, 7374, pp. 1-10. https://doi.org/10.1038/s41467-023-42205-6

TY - JOUR

T1 - Evaluation of pragmatic oxygenation measurement as a proxy for Covid-19 severity

AU - Swets, Maaike C.

AU - Kerr, Steven

AU - Scott-Brown, James

AU - Brown, Adam

AU - Gupta, Rishi K

AU - Millar, Jonathan

AU - Spata, Enti

AU - McCurrach, Fiona

AU - Bretherick, Andrew D

AU - Docherty, Annemarie B

AU - Harrison, David

AU - Rowan, Kathy

AU - Young, Neil

AU - Groeneveld, Geert H

AU - Dunning, Jake

AU - Nguyen-Van-Tam, Jonathan S.

AU - Openshaw, Peter

AU - Horby, Peter

AU - Harrison, Ewen M

AU - Staplin, Natalie

AU - Semple, Malcolm G

AU - Lone, Nazir I

AU - Baillie, J Kenneth

N1 - Funding Information: This work uses data provided by patients and collected by the NHS as part of their care and support. We are extremely grateful for the front-line NHS clinical and research staff and volunteer medical students who collected this data in challenging circumstances, and the generosity of the participants and their families for their individual contributions in these difficult times. We also acknowledge the support of Jeremy J Farrar (Wellcome Trust) and Nahoko Shindo (WHO). For the purpose of open access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. JKB gratefully acknowledges funding support from a Wellcome Trust Senior Research Fellowship (223164/Z/21/Z), UKRI grants MC_PC_20004, MC_PC_19025, MC_PC_1905, MRNO2995X/1, and MC_PC_20029, Sepsis Research (Fiona Elizabeth Agnew Trust), a BBSRC Institute Strategic Programme Grant to the Roslin Institute (BB/P013732/1, BB/P013759/1), and the UK Intensive Care Society. ISARIC4C work was supported by the National Institute for Health Research (NIHR), the Medical Research Council [MC_PC_19059] and by the NIHR Health Protection Research Unit (HPRU) in Emerging and Zoonotic Infections at University of Liverpool in partnership with Public Health England (PHE), in collaboration with Liverpool School of Tropical Medicine and the University of Oxford [200907], NIHR HPRU in Respiratory Infections at Imperial College London with PHE [200927], Wellcome Trust and Department for International Development [215091/Z/18/Z], and the Bill and Melinda Gates Foundation [OPP1209135], and Liverpool Experimental Cancer Medicine Centre (C18616/A25153), NIHR Biomedical Research Centre at Imperial College London [IS-BRC-1215-20013], EU Platform for European Preparedness Against (Re-) emerging Epidemics (PREPARE) [FP7 project 602525] and NIHR Clinical Research Network for providing infrastructure support for this research. Publisher Copyright: © 2023, The Author(s).

PY - 2023/11/15

Y1 - 2023/11/15

N2 - 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 푆/퐹 ratio.Because of the ceiling effect in oxyhaemoglobin saturation, 푆/퐹 ratio ceases to reflect pulmonary oxygenation function at high 푆푝푂2 values. We found that the correlation of 푆/퐹 with the reference standard (푃푎푂2/퐹퐼푂2 ratio) improves substantially when excluding 푆푝푂2 > 0.94 and refer to this measure as 푆/퐹94.Using observational data from 39,765 hospitalised COVID-19 patients, we demonstrate that 푆/퐹94 isn 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 samplesize using 푆/퐹94.We demonstrate that 푆/퐹94 is an effective intermediate outcome measure in COVID-19. It is a noninvasive measurement, representative of disease severity and provides greater statistical power.

AB - 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 푆/퐹 ratio.Because of the ceiling effect in oxyhaemoglobin saturation, 푆/퐹 ratio ceases to reflect pulmonary oxygenation function at high 푆푝푂2 values. We found that the correlation of 푆/퐹 with the reference standard (푃푎푂2/퐹퐼푂2 ratio) improves substantially when excluding 푆푝푂2 > 0.94 and refer to this measure as 푆/퐹94.Using observational data from 39,765 hospitalised COVID-19 patients, we demonstrate that 푆/퐹94 isn 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 samplesize using 푆/퐹94.We demonstrate that 푆/퐹94 is an effective intermediate outcome measure in COVID-19. It is a noninvasive measurement, representative of disease severity and provides greater statistical power.

U2 - 10.1038/s41467-023-42205-6

DO - 10.1038/s41467-023-42205-6

M3 - Article

C2 - 37968269

SN - 2041-1723

VL - 14

SP - 1

EP - 10

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 7374

ER -

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

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Projects

Translational genomics in critical care medicine

ISP 1 2017/22 Blueprints for Healthy Animals

ISP 3 2017/22 Improving Animal Health and Welfare

Cite this