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Register a new userSeverity and Mortality Prediction Models to Triage Indian COVID-19 Patients
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Samarth Bhatia
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As the second wave in India mitigates, COVID-19 has now infected about 29 million patients countrywide, leading to more than 350 thousand people dead. As the infections surged, the strain on the medical infrastructure in the country became apparent. While the country vaccinates its population, opening up the economy may lead to an increase in infection rates. In this scenario, it is essential to effectively utilize the limited hospital resources by an informed patient triaging system based on clinical parameters. Here, we present two interpretable machine learning models predicting the clinical outcomes, severity, and mortality, of the patients based on routine non-invasive surveillance of blood parameters from one of the largest cohorts of Indian patients at the day of admission. Patient severity and mortality prediction models achieved 86.3% and 88.06% accuracy, respectively, with an AUC-ROC of 0.91 and 0.92. We have integrated both the models in a user-friendly web app calculator, https://triage-COVID-19.herokuapp.com/, to showcase the potential deployment of such efforts at scale.
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Many countries are now experiencing the third wave of the COVID-19 pandemic straining the healthcare resources with an acute shortage of hospital beds and ventilators for the critically ill patients. This situation is especially worse in India with the second largest load of COVID-19 cases and a relatively resource-scarce medical infrastructure. Therefore, it becomes essential to triage the patients based on the severity of their disease and devote resources towards critically ill patients. Yan et al. 1 have published a very pertinent research that uses Machine learning (ML) methods to predict the outcome of COVID-19 patients based on their clinical parameters at the day of admission. They used the XGBoost algorithm, a type of ensemble model, to build the mortality prediction model. The final classifier is built through the sequential addition of multiple weak classifiers. The clinically operable decision rule was obtained from a single-tree XGBoost and used lactic dehydrogenase (LDH), lymphocyte and high-sensitivity C-reactive protein (hs-CRP) values. This decision tree achieved a 100% survival prediction and 81% mortality prediction. However, these models have several technical challenges and do not provide an out of the box solution that can be deployed for other populations as has been reported in the Matters Arising section of Yan et al. Here, we show the limitations of this model by deploying it on one of the largest datasets of COVID-19 patients containing detailed clinical parameters collected from India.
The unprecedented global crisis brought about by the COVID-19 pandemic has sparked numerous efforts to create predictive models for the detection and prognostication of SARS-CoV-2 infections with the goal of helping health systems allocate resources. Machine learning models, in particular, hold promise for their ability to leverage patient clinical information and medical images for prediction. However, most of the published COVID-19 prediction models thus far have little clinical utility due to methodological flaws and lack of appropriate validation. In this paper, we describe our methodology to develop and validate multi-modal models for COVID-19 mortality prediction using multi-center patient data. The models for COVID-19 mortality prediction were developed using retrospective data from Madrid, Spain (N=2547) and were externally validated in patient cohorts from a community hospital in New Jersey, USA (N=242) and an academic center in Seoul, Republic of Korea (N=336). The models we developed performed differently across various clinical settings, underscoring the need for a guided strategy when employing machine learning for clinical decision-making. We demonstrated that using features from both the structured electronic health records and chest X-ray imaging data resulted in better 30-day-mortality prediction performance across all three datasets (areas under the receiver operating characteristic curves: 0.85 (95% confidence interval: 0.83-0.87), 0.76 (0.70-0.82), and 0.95 (0.92-0.98)). We discuss the rationale for the decisions made at every step in developing the models and have made our code available to the research community. We employed the best machine learning practices for clinical model development. Our goal is to create a toolkit that would assist investigators and organizations in building multi-modal models for prediction, classification and/or optimization.
Objective: To conduct a meta-analysis of current studies that examined sex differences in severity and mortality in patients with COVID-19, and identify potential mechanisms underpinning these differences. Methods: We performed a systematic review to collate data from observational studies examining associations of sex differences with clinical outcomes of COVID-19. PubMed, Web of Science and four preprint servers were searched for relevant studies. Data were extracted and analyzed using meta-analysis where possible, with summary data presented otherwise. Publicly available bulk RNA sequencing (RNA-seq), single-cell RNA sequencing (scRNA-seq), and chromatin immunoprecipitation sequencing (ChIP-seq) data were analyzed to explore the potential mechanisms underlying the observed association. Results: 39 studies met inclusion criteria, representing 77932 patients, of which 41510 (53.3%) were males. Men were at a markedly increased risk of developing severe cases compared with women. Furthermore, the pooled odds ratio (OR) of mortality for male group compared with the female group indicated significant higher mortality rate for male. Data from scRNA-seq suggest that men have a higher amount of ACE2-expressing pulmonary alveolar type II cells than women. Sex-based immunological differences exist. The expression of androgen receptor (AR) is positively correlated with ACE2, and there is evidence that AR may directly regulate the expression of ACE2. Conclusions: This meta-analysis detected an increased severity and mortality rate in the male populations with COVID-19, which might be attributable to the sex-based differences in cellular compositions and immunological microenvironments of the lung. The host cell receptor ACE2 is likely regulated by AR signaling pathway, which is identified as a potential target for prevention and treatment of SARS-Cov-2 infections in men.
Machine Learning (ML) models typically require large-scale, balanced training data to be robust, generalizable, and effective in the context of healthcare. This has been a major issue for developing ML models for the coronavirus-disease 2019 (COVID-19) pandemic where data is highly imbalanced, particularly within electronic health records (EHR) research. Conventional approaches in ML use cross-entropy loss (CEL) that often suffers from poor margin classification. For the first time, we show that contrastive loss (CL) improves the performance of CEL especially for imbalanced EHR data and the related COVID-19 analyses. This study has been approved by the Institutional Review Board at the Icahn School of Medicine at Mount Sinai. We use EHR data from five hospitals within the Mount Sinai Health System (MSHS) to predict mortality, intubation, and intensive care unit (ICU) transfer in hospitalized COVID-19 patients over 24 and 48 hour time windows. We train two sequential architectures (RNN and RETAIN) using two loss functions (CEL and CL). Models are tested on full sample data set which contain all available data and restricted data set to emulate higher class imbalance.CL models consistently outperform CEL models with the restricted data set on these tasks with differences ranging from 0.04 to 0.15 for AUPRC and 0.05 to 0.1 for AUROC. For the restricted sample, only the CL model maintains proper clustering and is able to identify important features, such as pulse oximetry. CL outperforms CEL in instances of severe class imbalance, on three EHR outcomes with respect to three performance metrics: predictive power, clustering, and feature importance. We believe that the developed CL framework can be expanded and used for EHR ML work in general.
The black-box nature of machine learning models hinders the deployment of some high-accuracy models in medical diagnosis. It is risky to put ones life in the hands of models that medical researchers do not fully understand. However, through model interpretation, black-box models can promptly reveal significant biomarkers that medical practitioners may have overlooked due to the surge of infected patients in the COVID-19 pandemic. This research leverages a database of 92 patients with confirmed SARS-CoV-2 laboratory tests between 18th Jan. 2020 and 5th Mar. 2020, in Zhuhai, China, to identify biomarkers indicative of severity prediction. Through the interpretation of four machine learning models, decision tree, random forests, gradient boosted trees, and neural networks using permutation feature importance, Partial Dependence Plot (PDP), Individual Conditional Expectation (ICE), Accumulated Local Effects (ALE), Local Interpretable Model-agnostic Explanations (LIME), and Shapley Additive Explanation (SHAP), we identify an increase in N-Terminal pro-Brain Natriuretic Peptide (NTproBNP), C-Reaction Protein (CRP), and lactic dehydrogenase (LDH), a decrease in lymphocyte (LYM) is associated with severe infection and an increased risk of death, which is consistent with recent medical research on COVID-19 and other research using dedicated models. We further validate our methods on a large open dataset with 5644 confirmed patients from the Hospital Israelita Albert Einstein, at S~ao Paulo, Brazil from Kaggle, and unveil leukocytes, eosinophils, and platelets as three indicative biomarkers for COVID-19.
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