An Interpretable Machine Learning Framework for Accurate Severe vs Non-Severe COVID-19 Clinical Type Classification

Abstract

Effectively and efficiently diagnosing COVID-19 patients with accurate clinical type is essential to achieve optimal outcomes for the patients as well as reducing the risk of overloading the healthcare system. Currently, severe and non-severe COVID-19 types are differentiated by only a few features, which do not comprehensively characterize the complicated pathological, physiological, and immunological responses to SARS-CoV-2 invasion in different types. In this study, we recruited 214 confirmed COVID-19 patients in non-severe and 148 in severe type, from Wuhan, China. The patients’ comorbidity and symptoms (including 26 features), and laboratory testing results (26 features) upon admission were acquired as two input modalities. Exploratory analyses demonstrated that these features differed substantially between two clinical types. Machine learning random forest (RF) models based on features in each modality were developed and validated to classify COVID-19 clinical types. Using comorbidity/symptom and laboratory results as input independently, RF models achieved >90% and >95% predictive accuracy, respectively. Input features’ importance based on Gini impurity were further evaluated and top five features from each modality were identified (age, hypertension, cardiovascular disease, gender, diabetes; D-Dimer, hsTNI, absolute neutrophil count, IL-6, and LDH, in descending order). Combining top 10 multimodal features, RF model achieved >99% predictive accuracy. These findings shed light on how the human body reacts to SARS-CoV-2 invasion as a unity and provide insights on effectively evaluating COVID-19 patient’s severity and developing personalized treatment plans accordingly. We suggest that symptoms and comorbidities can be used as an initial screening tool for triaging, while laboratory results are applied when accuracy is the priority.Funding Statement: This study was jointly supported by the National Science Foundation for Young Scientists of China (81703201), the Natural Science Foundation for Young Scientists of Jiangsu Province (BK20171076), the Jiangsu Provincial Medical Innovation Team (CXTDA2017029), the Jiangsu Provincial Medical Youth Talent program (QNRC2016548), the Jiangsu Preventive Medicine Association program (Y2018086), the Lifting Program of Jiangsu Provincial Scientific and Technological Association, and the Jiangsu Government Scholarship for Overseas Studies.Declaration of Interests: The authors declare no competing interests in this study.Ethics Approval Statement: Patient-specific identifying information (e.g., name, address of residence) was removed from data collected for this study. This study was evaluated and approved by the IRB committee of Union Hospital, Wuhan, China (approval number: 2020-IEC-J-345).