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 S/F ratio. Because of the ceiling effect in oxyhaemoglobin saturation, S/F ratio ceases to reflect pulmonary oxygenation function at high {S}_{p}{O}_{2} values. We found that the correlation of S/F with the reference standard ({P}_{a}{O}_{2}/{F}_{I}{O}_{2} ratio) improves substantially when excluding {S}_{p}{O}_{2} > 0.94 and refer to this measure as S/{F}_{94}. Using observational data from 39,765 hospitalised COVID-19 patients, we demonstrate that 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}. We demonstrate that 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.