Fig. 4. Histopathological changes in cynomolgus and rhesus macaques during SARS-CoV-2 infection.

Areas of alveolar necrosis observed in cynomolgus macaques at 4/5 dpc with shrunken, eosinophilic cells within the alveolar walls (a, b), together with alveolar oedema (a, arrows; bar = 100 µm), type II pneumocyte hyperplasia and expanded alveolar spaces with inflammatory cell infiltration (b, arrows; bar = 100 µm). Occasional multinucleated cells are observed (b, insert; bar = 20 µm). Similar histopathological changes observed in rhesus macaques, including alveolar necrosis and areas with patchy alveolar oedema (c, arrow; bar = 100 µm), and accumulatios of alveolar macrophages (d, arrow; bar = 100 µm) and bronchial exudates (d, insert; bar = 50 µm). Histopathological changes with less severity observed at 14/15 dpc in cynomolgus macaques, with infiltration of mononuclear cells within alveolar spaces and bronchiolar lumen (e, arrows; bar = 100 µm) and perivascular cuffing (f, arrow; bar = 100 µm). Bronchiole regeneration (g, arrow; bar = 100 µm) and perivascular/peribronchiolar cuffing observed in rhesus macaques at 14/15 dpc (h, arrows; bar = 100 µm), together with BALT proliferation (h, *; bar = 100 µm). Representative images from 6 slides per animal at each time point.