Starting from December 2019, the COVID-19 pandemic has globally strained medical resources and caused significant mortality. It is commonly recognized that the severity of SARS-CoV-2 disease depends on both the comorbidity and the state of the patient's immune system, which is reflected in several biomarkers. The development of early diagnosis and disease severity prediction methods can reduce the burden on the health care system and increase the effectiveness of treatment and rehabilitation of patients with severe cases. This study aims to develop and validate an ensemble machine-learning model based on clinical and immunological features for severity risk assessment and post-COVID rehabilitation duration for SARS-CoV-2 patients. The dataset consisting of 35 features and 122 instances was collected from Lviv regional rehabilitation center. The dataset contains age, gender, weight, height, BMI, CAT, 6-minute walking test, pulse, external respiration function, oxygen saturation, and 15 immunological markers used to predict the relationship between disease duration and biomarkers using the machine learning approach. The predictions are assessed through an area under the receiver-operating curve, classification accuracy, precision, recall, and F1 score performance metrics. A new hybrid ensemble feature selection model for a post-COVID prediction system is proposed as an automatic feature cut-off rank identifier. A three-layer high accuracy stacking ensemble classification model for intelligent analysis of short medical datasets is presented. Together with weak predictors, the associative rules allowed improving the classification quality. The proposed ensemble allows using a random forest model as an aggregator for weak repressors' results generalization. The performance of the three-layer stacking ensemble classification model (AUC 0.978; CA 0.920; F1 score 0.921; precision 0.924; recall 0.920) was higher than five machine learning models, viz. tree algorithm with forward pruning; Naïve Bayes classifier; support vector machine with RBF kernel; logistic regression, and a calibrated learner with sigmoid function and decision threshold optimization. Aging-related biomarkers, viz. CD3+, CD4+, CD8+, CD22+ were examined to predict post-COVID rehabilitation duration. The best accuracy was reached in the case of the support vector machine with the linear kernel (MAPE = 0.0787) and random forest classifier (RMSE = 1.822). The proposed three-layer stacking ensemble classification model predicted SARS-CoV-2 disease severity based on the cytokines and physiological biomarkers. The results point out that changes in studied biomarkers associated with the severity of the disease can be used to monitor the severity and forecast the rehabilitation duration.
Keywords: COVID-19; biomarkers; ensemble classification; machine learning; severity prediction.