Who is most at risk of dying if infected with SARS-CoV-2? A mortality risk factor analysis using machine learning of COVID-19 patients over time in a large Mexican population
Authors: Liao Lauren D. , Hubbard Alan E. , Gutiérrez Juan Pablo , Juárez-Flores Arturo , Kikkawa Kendall , Gupta Ronit , Yarmolich Yana , de Jesús Ascencio-Montiel Iván , Bertozzi Stefano M. 
Published: January 2023

AbstractBackgroundCOVID-19 would kill fewer people if health programs can predict who is at higher risk of mortality because resources can be targeted to protect those people from infection. We predict mortality in a very large population in Mexico with machine learning using demographic variables and pre-existing conditions.MethodsWe conducted a population-based cohort study with over 1.4 million laboratory-confirmed COVID-19 patients using the Mexican social security database. Analysis is performed on data from March 2020 to November 2021 and over three phases: (1) from March to October in 2020, (2) from November 2020 to March 2021, and (3) from April to November 2021. We predict mortality using an ensemble machine learning method,super learner, and independently estimate the adjusted mortality relative risk of each pre-existing condition using targeted maximum likelihood estimation.ResultsSuper learner fit has a high predictive performance (C-statistic: 0.907), where age is the most predictive factor for mortality. After adjusting for demographic factors, renal disease, hypertension, diabetes, and obesity are the most impactful pre-existing conditions. Phase analysis shows that the adjusted mortality risk decreased over time while relative risk increased for each pre-existing condition.ConclusionsWhile age is the most important predictor of mortality, younger individuals with hypertension, diabetes and obesity are at comparable mortality risk as individuals who are 20 years older without any of the three conditions. Our model can be continuously updated to identify individuals who should most be protected against infection as the pandemic evolves.Key messagesWhat is already known on this topicStudies for Mexico and other countries have suggested that pre-existing conditions such as renal disease, diabetes, hypertension, and obesity are strongly associated with COVID-19 mortality. While age and the presence of pre-existing conditions have been shown to predict mortality, other studies have typically used less powerful statistical approaches, have had smaller sample sizes, and have not been able to describe changes over time.What this study addsThis study examines mortality risk in a very large population (> 60 M); it uses powerful ensemble machine learning methods that outperform regression analyses; and it demonstrates marked changes over time in the degree to which different risk factors predict mortality.How this study might affect research, practice or policyBecause we show an important improvement in predictive performance over traditional regression analyses, and the ability to update estimates as the pandemic evolves, we argue that these methods should be much more widely used to inform national programming in Mexico and elsewhere. Programs that assume that predictive models don’t change over time as variants emerge and as pre-existing immunity evolves due to vaccination and prior infection will not accurately predict mortality risk.