Figure 4.

Pathology aspects of lung and trachea. (A) Representative haematoxylin and eosin stained sections of normal, moderately and severely affected respiratory tissues at overview, 25x and 200x magnification. Lungs of SARS-CoV-2 infected animals with a clear hyperplasia of the Bronchus-Associated Lymphoid Tissue (BALT), consisting of activated lymphocytes that penetrate through the muscle layer of the bronch(iol)us into the lamina propria and submucosa (indicated in figure with ‘1’). Hyperplasia of bronchial epithelium visible as repeated bumps (2), cellular infiltrate into the submucosa (3) and exudate in the lumen (4) were also observed. The presence of hyper-plastic follicles led to obstruction of bronchiole (5). Some animals displayed desquamative interstitial pneumonia, with pulmonary macrophages in the alveoli and to a minor extent, lymphocytes and plasma cells (6). The alveolar epithelium (pneumocytes) exhibited squamous-like characteristics. Images are taken from placebo ferrets (‘normal’) or SARS-CoV-2 infected ferrets 14 or 21 dpi (‘moderate’, ‘severe’). (B-D) Pathology was summarized in an overall score ranging from 0-5 based on the parameters described in the materials and methods. Pathology score (B) and % of tissue affected (C) for lung tissue and pathology score for trachea (D). With exception of ‘Adult i.t.’ on 14 dpi (n = 2), all groups are n = 3. (E) Representative haematoxylin and eosin stained sections of normal, moderately and severely affected trachea tissue slides at 200x magnification. Pathological aberrations in the trachea consisted of hyperplasia (7), damage and pseudo-squamous characteristics of the epithelium (8) and infiltration of inflammatory cells into the submucosa and epithelium of the trachea (9). Images are taken from SARS-CoV-2 infected ferrets 5 (‘normal) or 21 dpi (‘moderate’, ‘severe’).Bars represent 200µm, 100µm and 50µm at respectively 25x, 100x and 200x magnification.