Derivation and Validation of Clinical Prediction Rule for COVID-19 Mortality in Ontario, Canada

Fisman, D.; Greer, A. L.; Tuite, A.

Background: SARS-CoV-2 is currently causing a high mortality global pandemic. However, the clinical spectrum of disease caused by this virus is broad, ranging from asymptomatic infection to cytokine storm with organ failure and death. Risk stratification of individuals with COVID-19 would be desirable for management, prioritization for trial enrollment, and risk stratification. We sought to develop a prediction rule for mortality due to COVID-19 in individuals with diagnosed infection in Ontario, Canada. Methods: Data from the Ontario provincial iPHIS system were extracted for the period from January 23 to May 15, 2020. Both logistic regression-based prediction rules, and a rule derived using a Cox proportional hazards model, were developed in half the study and validated in remaining patients. Sensitivity analyses were performed with varying approaches to missing data. Results: 21,922 COVID-19 cases were reported. Individuals assigned to the derivation and validation sets were broadly similar. Age and comorbidities (notably diabetes, renal disease and immune compromise) were strong predictors of mortality. Four point-based prediction rules were derived (base case, smoking excluded as a predictor, long-term care excluded as a predictor, and Cox model based). All rules displayed excellent discrimination (AUC for all rules > 0.92 ) and calibration (both by graphical inspection and P > 0.50 by Hosmer-Lemeshow test) in the derivation set. All rules performed well in the validation set and were robust to random replacement of missing variables, and to the assumption that missing variables indicated absence of the comorbidity or characteristic in question. Conclusions: We were able to use a public health case-management data system to derive and internally validate four accurate, well-calibrated and robust clinical prediction rules for COVID-19 mortality in Ontario, Canada. While these rules need external validation, they may be a useful tool for clinical management, risk stratification, and clinical trials.