Nature Communications November 2023

The ISARIC4C team have demonstrated that S/F94 is an effective intermediate outcome measure in COVID-19. It is said to be a non-invasive measurement, representative of disease severity and provides greater statistical power. The investigators 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. ISARIC4C 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, they demonstrate that S/F94 is predictive of mortality, and compare the sample sizes required for trials using four different outcome measures. In this paper, they show that a significant difference in outcome could be detected with the smallest sample size using S/F94.