COVID-19 screening with digital holographic microscopy using intra-patient probability functions of spatio-temporal bio-optical attributes.

We present an automated method for COVID-19 screening using the intra-patient population distributions of bio-optical attributes extracted from digital holographic microscopy reconstructed red blood cells. Whereas previous approaches have aimed to identify infection by classifying individual cells, here, we propose an approach to incorporate the attribute distribution information from the population of a given human subjects' cells into our classification scheme and directly classify subjects at the patient level. To capture the intra-patient distribution information in a generalized way, we propose an approach based on the Bag-of-Features (BoF) methodology to transform histograms of bio-optical attribute distributions into feature vectors for classification via a linear support vector machine. We compare our approach with simpler classifiers directly using summary statistics such as mean, standard deviation, skewness, and kurtosis of the distributions. We also compare to a k-nearest neighbor classifier using the Kolmogorov-Smirnov distance as a distance metric between the attribute distributions of each subject. We lastly compare our approach to previously published methods for classification of individual red blood cells. In each case, the methodology proposed in this paper provides the highest patient classification performance, correctly classifying 22 out of 24 individuals and achieving 91.67% classification accuracy with 90.00% sensitivity and 92.86% specificity. The incorporation of distribution information for classification additionally led to the identification of a singular temporal-based bio-optical attribute capable of highly accurate patient classification. To the best of our knowledge, this is the first report of a machine learning approach using the intra-patient probability distribution information of bio-optical attributes obtained from digital holographic microscopy for disease screening.