Development and validation of a clinical risk score to predict SARS-CoV-2 infection in emergency department patients: The CCEDRRN COVID-19 Infection Score (CCIS)

Abstract Background Clinicians face decisions around the need for severe acute respiratory coronavirus 2 (SARS-CoV-2) testing, patient isolation, and empiric therapy when patients arrive in acute care hospitals. Our objective was to develop a risk score that can accurately quantify a patient’s probability of SARS-CoV-2 infection. Methods This observational study enrolled consecutive adults who presented to the emergency departments of 32 hospitals participating in Canadian COVID-19 Emergency Department Rapid Response Network (CCEDRRN) and were tested for SARS-CoV-2. We divided our study population by randomly assigning study sites into derivation (75%) and validation (25%) cohorts We pre-specified predictors and used multiple imputation for variables with incomplete data. In the derivation cohort, we fit models using logistic regression, with spline functions for continuous variables, to predict the primary outcome of a positive SARS-CoV-2 nucleic acid test. We used a fast step-down procedure to select a concise model. The final reduced model had points allocated to each variable based on their predictive strength. We then validated the model in the geographically distinct validation cohort. Findings We derived a ten-item CCEDRRN COVID-19 Infection Score using data from 21,743 patients. This score included variables from history and physical examination, and an indicator of local disease incidence. The score had a C-statistic of 0.838 with excellent calibration. We externally validated the rule in 5,295 patients. The score maintained excellent discrimination and calibration, and had superior performance compared to another previously published risk score. Interpretation The CCEDRRN COVID-19 Infection Score uses clinical characteristics and publicly available indicators of disease incidence to quantify a patient’s probability of SARS-CoV-2 infection. The score can identify patients at sufficiently high risk of SARS-CoV-2 infection to warrant isolation and empiric therapy prior to test confirmation, while also identifying patients at sufficiently low risk of infection that they may not need testing. Funding The network is funded by the Canadian Institutes of Health Research (447679), BC Academic Health Science Network Society, BioTalent Canada, Genome BC (COV024; VAC007), Ontario Ministry of Colleges and Universities (C-655-2129), the Saskatchewan Health Research Foundation (5357) and the Fondation CHU de Quebec (Octroi #4007). These organizations are not-for-profit, and had no role in study conduct, analysis, or manuscript preparation.