Development and evaluation of a machine learning-based in-hospital COvid-19 Disease Outcome Predictor (CODOP): a multicontinental retrospective study

Background: More contagious SARS-CoV-2 virus variants, breakthrough infections, waning immunity, and differential access to COVID-19 vaccines account for the worst yet numbers of hospitalization and deaths during the COVID-19 pandemic, particularly in resource-limited countries. There is an urgent need for clinically valuable, generalizable, and parsimonious triage tools assisting appropriate allocation of hospital resources during the pandemic. We aimed to develop and extensively validate a machine learning-based tool for accurately predicting the clinical outcome of hospitalized COVID-19 patients. Methods: CODOP was built using modified stable iterative variable selection and linear regression with lasso regularisation. To avoid generalization problems, CODOP was trained and tested with three time-sliced and geographically distinct cohorts encompassing 40 511 blood-based analyses of COVID-19 patients from more than 110 hospitals in Spain and the USA during 2020-21. We assessed the discriminative ability of the model using the Area Under the Receiving Operative Curve (AUROC) as well as horizon and Kaplan-Meier risk stratification analyses. To reckon the fluctuating pressure levels in hospitals through the pandemic, we offer two online CODOP calculators suited for undertriage or overtriage scenarios. We challenged their generalizability and clinical utility throughout an evaluation with datasets gathered in five hospitals from three Latin American countries.  Findings: CODOP uses 12 clinical parameters commonly measured at hospital admission and associated with the pathophysiology of COVID-19. CODOP reaches high discriminative ability up to nine days before clinical resolution (AUROC: 0·90-0·96, 95% CI 0·879-0·970), it is well calibrated, and it enables an effective dynamic risk stratification during hospitalization. The two CODOP online calculators predicted the clinical outcome of the majority of patients (73-100% sensitivity and 84-100% specificity) from the distinctive Latin American evaluation cohort. Interpretation: The high predictive performance of CODOP in geographically disperse patient cohorts and the easiness-of-use, strongly suggest its clinical utility as a global triage tool, particularly in resource-limited countries. Funding: The Max Planck Society. Declaration of Interest: The authors declare no conflict of interest. Ethical Approval: This study was approved by the Provincial Research Ethics Committee of Malaga (Spain) and the Institutional Research Ethics Committees of each participating hospital.