Development of a Multivariable Model for COVID-19 Risk Stratification Based on Gradient Boosting Decision Trees

Abstract Importance Population stratification of the adult population in Ontario, Canada by their risk of COVID-19 complications can support rapid pandemic response, resource allocation, and decision making. Objective To develop and validate a multivariable model to predict risk of hospitalization due to COVID-19 severity from routinely collected health records of the entire adult population of Ontario, Canada. Design, Setting, and Participants This cohort study included 36,323 adult patients (age ≥ 18 years) from the province of Ontario, Canada, who tested positive for SARS-CoV-2 nucleic acid by polymerase chain reaction between February 2 and October 5, 2020, and followed up through November 5, 2020. Patients living in long-term care facilities were excluded from the analysis. Main Outcomes and Measures Risk of hospitalization within 30 days of COVID-19 diagnosis was estimated via Gradient Boosting Decision Trees, and risk factor importance was examined via Shapley values. Results The study cohort included 36,323 patients with majority female sex (18,895 [52.02%]) and median (IQR) age of 45 (31-58) years. The cohort had a hospitalization rate of 7.11% (2,583 hospitalizations) with median (IQR) time to hospitalization of 1 (0-5) days, and a mortality rate of 2.49% (906 deaths) with median (IQR) time to death of 12 (6-27) days. In contrast to patients who were not hospitalized, those who were hospitalized had a higher median age (64 years vs 43 years, p-value < 0.001), majority male (56.25% vs 47.35%, p-value<0.001), and had a higher median [IQR] number of comorbidities (3 [2-6] vs 1 [0-3], p-value<0.001). Patients were randomly split into development (n=29,058, 80%) and held-out validation (n=7,265, 20%) cohorts. The final Gradient Boosting model was built using the XGBoost algorithm and achieved high discrimination (development cohort: mean area under the receiver operating characteristic curve across the five folds of 0.852; held-out validation cohort: 0.8475) as well as excellent calibration (R 2 =0.998, slope=1.01, intercept=-0.01). The patients who scored at the top 10% in the validation cohort captured 47.41% of the actual hospitalizations, whereas those scored at the top 30% captured 80.56%. Patients in the held-out validation cohort (n=7,265) with a score of at least 0.5 (n=2,149, 29.58%) had a 20.29% hospitalization rate (positive predictive value 20.29%) compared with 2.2% hospitalization rate for those with a score less than 0.5 (n=5,116, 70.42%; negative predictive value 97.8%). Aside from age, gender and number of comorbidities, the features that most contribute to model predictions were: history of abnormal blood levels of creatinine, neutrophils and leukocytes, geography and chronic kidney disease. Conclusions A risk stratification model has been developed and validated using unique, de-identified, and linked routinely collected health administrative data available in Ontario, Canada. The final XGBoost model showed a high discrimination rate, with the potential utility to stratify patients at risk of serious COVID-19 outcomes. This model demonstrates that routinely collected health system data can be successfully leveraged as a proxy for the potential risk of severe COVID-19 complications. Specifically, past laboratory results and demographic factors provide a strong signal for identifying patients who are susceptible to complications. The model can support population risk stratification that informs patients’ protection most at risk for severe COVID-19 complications.

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