External validation of the ISARIC 4C Mortality Score for hospitalized patients with COVID-19 in Tunisia

Abstract Estimating mortality risk in hospitalized patients with COVID-19 infection may help clinicians to early triage patients with poor prognostic outcome. The Coronavirus Clinical Characterization Consortium Mortality Score (4C Score) is one of the predictive models that was externally validated in large cohorts. However, its use may be limited in population with quite different demographic and epidemiologic features. Objective To externally validate the 4 C score in a large Tunisian population Methods Multicenter retrospective cohort study of patients aged ≥ 14 years, hospitalized with the diagnosis of COVID-19. The primary outcome was in-hospital mortality, need for ICU admission and combined outcome (in-hospital mortality and/or ICU admission). We calculated the area under the receiver operating characteristic (ROC) curve (C statistics) for the 4C Mortality Score to assess the discriminatory power of the 4C Mortality Score for predicting outcomes. To assess calibration of the model, we used the Hosmer-Lemeshow goodness-of-fit test. Results 2327 patients with diagnosis of COVID-19 based on positive RT-PCR assay or rapid antigen test of a nasopharyngeal swab were included for final analysis. Median time between symptoms start and hospital admission was 4 days [2-7], and 69.2% needed oxygen therapy at hospital admission. In-hospital mortality was 15.4% (n=358); most deaths (11%, n=257) occurred in the ICU. Mortality rates within the 4C Mortality Score risk groups were 0.6% (Low), 8.7% (Intermediate), 53.1% (High), and 37.7% (Very High). The score achieved a good estimated discrimination when predicting death (C-statistic:0.86; 95%, CI [0.84-0.88]), ICU admission (C-statistic: 0.69; 95%, CI [0.65-0.72]) and the combined outcome (C-statistic:0.79; 95%, CI [0.77-0.81]). The calibration plot indicated good calibration for both in-hospial mortality and combined outcome (HosmerLemeshow goodness-of-fit test p value of 0.86 and 0.28 respectively). Our study represents a new external validation of the 4C score in COVID-19 patients with high reliability in predicting disease severity. These findings imply that the 4C Mortality Score may be generalized to patients with COVID-19 regardless of ethnicity and healthcare system.