The recent Coronavirus Disease 2019 (COVID-19) pandemic has put a tremendous burden on global health systems. Medical practitioners are under great pressure for reliable screening of suspected cases employing adjunct diagnostic tools to standard point-of-care testing methodology. Chest X-rays (CXRs) are appearing as a prospective diagnostic tool with easy-to-acquire, low-cost and less cross-contamination risk features. Artificial intelligence (AI)-attributed CXR evaluation has shown great potential for distinguishing COVID-19-induced pneumonia from other associated clinical instances. However, one of the associated challenges with diagnostic imaging-based modeling is incorrect feature attribution, which leads the model to learn misguiding disease patterns, causing wrong predictions. Here, we demonstrate an effective deep learning-based methodology to mitigate the problem, thereby allowing the classification algorithm to learn from relevant features. The proposed deep-learning framework consists of an ensemble of convolutional neural network (CNN) models focusing on both global and local pathological features from CXR lung images, while the latter is extracted using a multi-instance learning scheme and a local attention mechanism. An inspection of a series of backbone CNN models using global and local features, and an ensemble of both features, trained from high-quality CXR images of 1311 patients, further augmented for achieving the symmetry in class distribution, to localize lung pathological features followed by the classification of COVID-19 and other related pneumonia, shows that a DenseNet161 architecture outperforms all other models, as evaluated on an independent test set of 159 patients with confirmed cases. Specifically, an ensemble of DenseNet161 models with global and local attention-based features achieve an average balanced accuracy of 91.2%, average precision of 92.4%, and F1-score of 91.9% in a multi-label classification framework comprising COVID-19, pneumonia, and control classes. The DenseNet161 ensembles were also found to be statistically significant from all other models in a comprehensive statistical analysis. The current study demonstrated that the proposed deep learning-based algorithm can accurately identify the COVID-19-related pneumonia in CXR images, along with differentiating non-COVID-19-associated pneumonia with high specificity, by effectively alleviating the incorrect feature attribution problem, and exploiting an enhanced feature descriptor.
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