Machine Learning for Real-World Evidence Analysis of COVID-19 Pharmacotherapy (preprint)

Introduction: Real-world data generated from clinical practice can be used to analyze the real-world evidence (RWE) of COVID-19 pharmacotherapy and validate the results of randomized clinical trials (RCTs). Machine learning (ML) methods are being used in RWE and are promising tools for precision-medicine. In this study, ML methods are applied to study the efficacy of therapies on COVID-19 hospital admissions in the Valencian Region in Spain. Methods: 5244 and 1312 COVID-19 hospital admissions - dated between January 2020 and January 2021 from 10 health departments, were used respectively for training and validation of separate treatment-effect models (TE-ML) for remdesivir, corticosteroids, tocilizumab, lopinavir-ritonavir, azithromycin and chloroquine/hydroxychloroquine. 2390 admissions from 2 additional health departments were reserved as an independent test to analyze retrospectively the survival benefits of therapies in the population selected by the TE-ML models using cox-proportional hazard models. TE-ML models were adjusted using treatment propensity scores to control for pre-treatment confounding variables associated to outcome and further evaluated for futility. ML architecture was based on boosted decision-trees. Results: In the populations identified by the TE-ML models, only Remdesivir and Tocilizumab were significantly associated with an increase in survival time, with hazard ratios of 0.41 (P = 0.04) and 0.21 (P = 0.001), respectively. No survival benefits from chloroquine derivatives, lopinavir-ritonavir and azithromycin were demonstrated. Tools to explain the predictions of TE-ML models are explored at patient-level as potential tools for personalized decision making and precision medicine. Conclusion: ML methods are suitable tools toward RWE analysis of COVID-19 pharmacotherapies. Results obtained reproduce published results on RWE and validate the results from RCTs.

UMLS-ChestNet: A deep convolutional neural network for radiological findings, differential diagnoses and localizations of COVID-19 in chest x-rays (preprint)

In this work we present a method for the detection of radiological findings, their location and differential diagnoses from chest x-rays. Unlike prior works that focus on the detection of few pathologies, we use a hierarchical taxonomy mapped to the Unified Medical Language System (UMLS) terminology to identify 189 radiological findings, 22 differential diagnosis and 122 anatomic locations, including ground glass opacities, infiltrates, consolidations and other radiological findings compatible with COVID-19. We train the system on one large database of 92,594 frontal chest x-rays (AP or PA, standing, supine or decubitus) and a second database of 2,065 frontal images of COVID-19 patients identified by at least one positive Polymerase Chain Reaction (PCR) test. The reference labels are obtained through natural language processing of the radiological reports. On 23,159 test images, the proposed neural network obtains an AUC of 0.94 for the diagnosis of COVID-19. To our knowledge, this work uses the largest chest x-ray dataset of COVID-19 positive cases to date and is the first one to use a hierarchical labeling schema and to provide interpretability of the results, not only by using network attention methods, but also by indicating the radiological findings that have led to the diagnosis.

BIMCV COVID-19+: a large annotated dataset of RX and CT images from COVID-19 patients (preprint)

This paper describes BIMCV COVID-19+, a large dataset from the Valencian Region Medical ImageBank (BIMCV) containing chest X-ray images CXR (CR, DX) and computed tomography (CT) imaging of COVID-19+ patients along with their radiological findings and locations, pathologies, radiological reports (in Spanish), DICOM metadata, Polymerase chain reaction (PCR), Immunoglobulin G (IgG) and Immunoglobulin M (IgM) diagnostic antibody tests. The findings have been mapped onto standard Unified Medical Language System (UMLS) terminology and cover a wide spectrum of thoracic entities, unlike the considerably more reduced number of entities annotated in previous datasets. Images are stored in high resolution and entities are localized with anatomical labels and stored in a Medical Imaging Data Structure (MIDS) format. In addition, 10 images were annotated by a team of radiologists to include semantic segmentation of radiological findings. This first iteration of the database includes 1,380 CX, 885 DX and 163 CT studies from 1,311 COVID-19+ patients. This is, to the best of our knowledge, the largest COVID-19+ dataset of images available in an open format. The dataset can be downloaded from http://bimcv.cipf.es/bimcv-projects/bimcv-covid19.