A multiple instance learning approach for detecting COVID-19 in peripheral blood smears

A wide variety of diseases are commonly diagnosed via the visual examination of cell morphology within a peripheral blood smear. For certain diseases, such as COVID-19, morphological impact across the multitude of blood cell types is still poorly understood. In this paper, we present a multiple instance learning-based approach to aggregate high-resolution morphological information across many blood cells and cell types to automatically diagnose disease at a per-patient level. We integrated image and diagnostic information from across 236 patients to demonstrate not only that there is a significant link between blood and a patient’s COVID-19 infection status, but also that novel machine learning approaches offer a powerful and scalable means to analyze peripheral blood smears. Our results both backup and enhance hematological findings relating blood cell morphology to COVID-19, and offer a high diagnostic efficacy; with a 79% accuracy and a ROC-AUC of 0.90. Author summary In this paper, we present a multiple instance learning-based approach to aggregate high-resolution morphological information across many blood cells and cell types to automatically diagnose COVID-19 at a per-patient level. We integrated image and diagnostic information from 236 patients to demonstrate not only that there is a significant link between blood and a patient’s COVID-19 infection status, but also that novel machine learning approaches offer a powerful and scalable means to analyze peripheral blood smears. Our results both backup and enhance hematological findings relating blood cell morphology to COVID-19, and offer high diagnostic accuracy. Besides the final aggregated decision, the proposed attention mechanism also provides cell-type importance, which can help pathologists to build valuable insights on which cell types are more diagnostically relevant, opening a window into improving the explainability of deep optical blood analysis approaches.