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In BMC medical research methodology

BACKGROUND : The high number of COVID-19 deaths is a serious threat to the world. Demographic and clinical biomarkers are significantly associated with the mortality risk of this disease. This study aimed to implement Generalized Neural Additive Model (GNAM) as an interpretable machine learning method to predict the COVID-19 mortality of patients.

METHODS : This cohort study included 2181 COVID-19 patients admitted from February 2020 to July 2021 in Sina and Besat hospitals in Hamadan, west of Iran. A total of 22 baseline features including patients' demographic information and clinical biomarkers were collected. Four strategies including removing missing values, mean, K-Nearest Neighbor (KNN), and Multivariate Imputation by Chained Equations (MICE) imputation methods were used to deal with missing data. Firstly, the important features for predicting binary outcome (1: death, 0: recovery) were selected using the Random Forest (RF) method. Also, synthetic minority over-sampling technique (SMOTE) method was used for handling imbalanced data. Next, considering the selected features, the predictive performance of GNAM for predicting mortality outcome was compared with logistic regression, RF, generalized additive model (GAMs), gradient boosting decision tree (GBDT), and deep neural networks (DNNs) classification models. Each model trained on fifty different subsets of a train-test dataset to ensure a model performance. The average accuracy, F1-score and area under the curve (AUC) evaluation indices were used for comparison of the predictive performance of the models.

RESULTS : Out of the 2181 COVID-19 patients, 624 died during hospitalization and 1557 recovered. The missing rate was 3 percent for each patient. The mean age of dead patients (71.17 ± 14.44 years) was statistically significant higher than recovered patients (58.25 ± 16.52 years). Based on RF, 10 features with the highest relative importance were selected as the best influential features; including blood urea nitrogen (BUN), lymphocytes (Lym), age, blood sugar (BS), serum glutamic-oxaloacetic transaminase (SGOT), monocytes (Mono), blood creatinine (CR), neutrophils (NUT), alkaline phosphatase (ALP) and hematocrit (HCT). The results of predictive performance comparisons showed GNAM with the mean accuracy, F1-score, and mean AUC in the test dataset of 0.847, 0.691, and 0.774, respectively, had the best performance. The smooth function graphs learned from the GNAM were descending for the Lym and ascending for the other important features.

CONCLUSIONS : Interpretable GNAM can perform well in predicting the mortality of COVID-19 patients. Therefore, the use of such a reliable model can help physicians to prioritize some important demographic and clinical biomarkers by identifying the effective features and the type of predictive trend in disease progression.

Moslehi Samad, Mahjub Hossein, Farhadian Maryam, Soltanian Ali Reza, Mamani Mojgan


COVID-19, Feature selection, Generalized neural additive, Laboratory markers, Machine learning, Prediction