Computational pathology reveals unique spatial patterns of immune response in H&E images from COVID-19 autopsies:...

Purpose: We used computerized image analysis and machine learning approaches to characterize spatial arrangement features of the immune response from digitized autopsied H&E tissue images of the lung in coronavirus disease 2019 (COVID-19) patients. Additionally, we applied our approach to tease out potential morphometric differences from autopsies of patients who succumbed to COVID-19 versus H1N1. Approach: H&E lung whole slide images from autopsy specimens of nine COVID-19 and two H1N1 patients were computationally interrogated. 606 image patches ( $$ per patient) of $$ were extracted from the 11 autopsied patient studies. A watershed-based segmentation approach in conjunction with a machine learning classifier was employed to identify two types of nuclei families: lymphocytes and non-lymphocytes (i.e., other nucleated cells such as pneumocytes, macrophages, and neutrophils). Based off the proximity of the individual nuclei, clusters for each nuclei family were constructed. For each of the resulting clusters, a series of quantitative measurements relating to architecture and density of nuclei clusters were calculated. A receiver operating characteristics-based feature selection method, violin plots, and the t-distributed stochastic neighbor embedding algorithm were employed to study differences in immune patterns. Results: In COVID-19, the immune response consistently showed multiple small-size lymphocyte clusters, suggesting that lymphocyte response is rather modest, possibly due to lymphocytopenia. In H1N1, we found larger lymphocyte clusters that were proximal to large clusters of non-lymphocytes, a possible reflection of increased prevalence of macrophages and other immune cells. Conclusion: Our study shows the potential of computational pathology to uncover immune response features that may not be obvious by routine histopathology visual inspection.