Fig. 2.

Histopathological evidence of alveolar damage, inflammation and SARS-CoV-2 infection in COVID-19 lungs. A. Severe and diffuse alveolar damage. Low magnification images (a, b, x2.5) show diffuse end-stage alveolar damage, with patchy inflammatory infiltrates. Higher magnification images better demonstrate massive disruption of alveolar structures and hyaline membranes (c, x20) and detachment of epithelial cells from the alveolar wall (d, x40). B. Moderate inflammatory infiltration. In most patients, lungs were sparsely infiltrated by clusters of inflammatory cells (a, 2.5x), largely composed of CD4⁺ helper and CD8⁺ suppressor lymphocytes (b, and c respectively, 2.5x), as well as of CD163⁺ histiocytes (d, 2.5x). C. Detection of SARS-CoV-2 RNA and Spike protein. In situ hybridization for SARS-CoV-2 RNA revealed extensive positivity in the cytoplasm of several alveolar cells (shown for one representative patient in a-d, x10; e, x20, f, x 40). Cuboidal pneumocytes (g, 20x) and several atypical cells (h, 40x, showing a bi-nucleated cell with a large inclusion body) were also positive for the expression of the Spike protein. Nuclei are stained with nuclear fast red.