ISARIC-4C Mortality Score overestimates risk of death due to COVID-19 in Australian ICU patients: a validation cohort study

Objective: To assess the performance of the UK International Severe Acute Respiratory and Emerging Infections Consortium (ISARIC) Coronavirus Clinical Characterisation Consortium (4C) Mortality Score for predicting mortality in Australian patients with coronavirus disease 2019 (COVID-19) requiring intensive care unit (ICU) admission. Design: Multicentre, prospective, observational cohort study. Setting: 78 Australian ICUs participating in the SPRINT-SARI (Short Period Incidence Study of Severe Acute Respiratory Infection) Australia study of COVID-19. Participants: Patients aged 16 years or older admitted to participating Australian ICUs with polymerase chain reaction (PCR)-confirmed COVID-19 between 27 February and 10 October 2020. Main outcome measures: ISARIC-4C Mortality Score, calculated at the time of ICU admission. The primary outcome was observed versus predicted in-hospital mortality (by 4C Mortality and APACHE II). Results: 461 patients admitted to a participating ICU were included. 149 (32%) had complete data to calculate a 4C Mortality Score without imputation. Overall, 61/461 patients (13.2%) died, 16.9% lower than the comparable ISARIC-4C cohort in the United Kingdom. In patients with complete data, the median (interquartile range [IQR]) 4C Mortality Score was 10.0 (IQR, 8.0–13.0) and the observed mortality was 16.1% (24/149) versus 22.9% median predicted risk of death. The 4C Mortality Score discriminatory performance measured by the area under the receiver operating characteristic curve (AUROC) was 0.79 (95% CI, 0.68–0.90), similar to its performance in the original ISARIC-4C UK cohort (0.77) and not superior to APACHE II (AUROC, 0.81; 95% CI, 0.75–0.87). Conclusions: When calculated at the time of ICU admission, the 4C Mortality Score consistently overestimated the risk of death for Australian ICU patients with COVID-19. The 4C Mortality Score may need to be individually recalibrated for use outside the UK and in different hospital settings.