ABSTRACT: STUDY OBJECTIVE:The goal of this study is to create a predictive, interpretable model of early hospital respiratory failure among emergency department (ED) patients admitted with coronavirus disease 2019 (COVID-19). METHODS:This was an observational, retrospective, cohort study from a 9-ED health system of admitted adult patients with severe acute respiratory syndrome coronavirus 2 (COVID-19) and an oxygen requirement less than or equal to 6 L/min. We sought to predict respiratory failure within 24 hours of admission as defined by oxygen requirement of greater than 10 L/min by low-flow device, high-flow device, noninvasive or invasive ventilation, or death. Predictive models were compared with the Elixhauser Comorbidity Index, quick Sequential [Sepsis-related] Organ Failure Assessment, and the CURB-65 pneumonia severity score. RESULTS:During the study period, from March 1 to April 27, 2020, 1,792 patients were admitted with COVID-19, 620 (35%) of whom had respiratory failure in the ED. Of the remaining 1,172 admitted patients, 144 (12.3%) met the composite endpoint within the first 24 hours of hospitalization. On the independent test cohort, both a novel bedside scoring system, the quick COVID-19 Severity Index (area under receiver operating characteristic curve mean 0.81 [95% confidence interval {CI} 0.73 to 0.89]), and a machine-learning model, the COVID-19 Severity Index (mean 0.76 [95% CI 0.65 to 0.86]), outperformed the Elixhauser mortality index (mean 0.61 [95% CI 0.51 to 0.70]), CURB-65 (0.50 [95% CI 0.40 to 0.60]), and quick Sequential [Sepsis-related] Organ Failure Assessment (0.59 [95% CI 0.50 to 0.68]). A low quick COVID-19 Severity Index score was associated with a less than 5% risk of respiratory decompensation in the validation cohort. CONCLUSION:A significant proportion of admitted COVID-19 patients progress to respiratory failure within 24 hours of admission. These events are accurately predicted with bedside respiratory examination findings within a simple scoring system.