Fig. 2: Acute SARS-CoV-2 infection is highly cytopathic and causes extensive damage to human lung structures.

a, Haematoxylin and eosin (H&E) staining of human lung tissue from a SARS-CoV-2-infected LoM two days after exposure. n = 6. Scale bar, 100 μm. Arrows indicate protein globules. b–d, Immunohistochemical staining for virus nucleoprotein in human lung tissue of LoM two days after exposure to SARS-CoV-2. Nucleoprotein-positive cells, brown. Scale bars, 100 μm (b), 50 μm (c, d). n = 6. e–g, Martius Scarlet Blue staining of human lung tissue from naive LoM (n = 6) (e) and SARS-CoV-2 infected LoM two days after exposure (n = 6) (f, g). Fibrin, red; collagen, blue. Scale bars, 50 μm. Arrows indicate the presence of fibrin (red) in alveoli (f) or thrombi (g) of occluded vessels. h–l, Electron microscopy analysis of SARS-CoV-2-infected human lung tissue of LoM at two days after exposure (n = 3). h, Uninfected alveolar type-2 pneumocytes in an alveolus-like structure. Scale bar, 2 μm. i, SARS-CoV-2-infected alveolar type-2 pneumocyte. Higher-magnification images of boxed areas show virus particles with dense nucleocapsids in the rough endoplasmic reticulum. Scale bars, 2 μm (left), 1 μm (centre), 200 nm (right). j, Degenerative SARS-CoV-2-infected cell in the alveolar space. Arrows indicate virus-filled vesicles. Scale bars, 1 μm (left), 200 nm (centre), 100 nm (right). k, l, Blood vessels containing virions, fibrillar protein and cell debris. Scale bars, 5 μm (k left), 500 nm (k right), 2 μm (l right), 200 nm (l left). AS, alveolar space; AT1, alveolar type-1 pneumocytes; AT2, alveolar type-2 pneumocytes; BV, blood vessel; C, collagen; G, glycogen; LB, lamellar body; M, mitochondria; MO, monocyte; MV, microvilli; RER, rough endoplasmic reticulum. In c, i–l, black boxes indicate areas of higher magnification. n, number of biologically independent lung tissues analysed.