Multiscale 3-dimensional pathology findings of COVID-19 diseased lung using high-resolution cleared tissue microscopy

Li, Guang; Fox, Sharon E.; Summa, Brian; Hu, Bihe; Wenk, Carola; Akmatbekov, Aibek; Harbert, Jack L.; Vander Heide, Richard S.; Brown, J. Quincy

The study of pulmonary samples from individuals who have died as a direct result of COVID-19 infection is vital to our understanding of the pathogenesis of this disease. Histopathologic studies of lung tissue from autopsy of patients with COVID-19 specific mortality are only just emerging. All existing reports have relied on traditional 2-dimensional slide-based histological methods for specimen preparation. However, emerging methods for high-resolution, massively multiscale imaging of tissue microstructure using fluorescence labeling and tissue clearing methods enable the acquisition of tissue histology in 3-dimensions, that could open new insights into the nature of SARS-Cov-2 infection and COVID-19 disease processes. In this article, we present the first 3-dimensional images of lung autopsy tissues taken from a COVID-19 patient, including 3D “virtual histology” of cubic-millimeter volumes of the diseased lung, providing unique insights into disease processes contributing to mortality that could inform frontline treatment decisions.