Lung Findings Macroscopic Findings. Lungs from all patients were increased in volume, firm, edematous, and congested with diffuse pleural thickening and pleural effusion. Cut surface showed consolidation of lobes and red congested areas, with thickening of the interstitial septa and pulmonary edema (Figure 1A1). Subsegmental pulmonary embolism was seen in 5 cases. Figure 1. Pathological findings in lung. A1, Lungs showed an increase in volume and were firmer and heavier than normal. A2 and A3, Light microscopic analysis shows parenchymal multifocal damage with intraalveolar inflammation, fibrin, and hyaline membranes consistent with a diagnosis of diffuse alveolar damage. Both acute exudative inflammatory process and fibrous proliferative phase were found. A3 and A4, Hyperplasia of type II pneumocyte, characterized by amphophilic cytoplasm, large nuclei, and prominent nucleoli, are shown (arrows). B1, Alveolar duct fibrosis. B2, Fibrin thrombi in capillaries. B3, Vascular injury including vessel vasculitis and vascular edema. B4, Pleural fibrosis. Abbreviation: H&E, haematoxylin and eosin. Scale bars: A2, 14 µm; A3–B3, 7 µm; B4, 21 µm. Microscopic Findings. A range of common lung findings were seen on light microscopy. Parenchymal multifocal damage with intraalveolar exudative and proliferative inflammation (Figure 1A2), with fibrin, hyaline membranes (Figure 1A3) consistent with a diagnosis of diffuse alveolar damage (Table 3). Organizing pneumonia with fibrosis and type II pneumocyte hyperplasia, amphophilic cytoplasm, large nuclei, and prominent nucleoli, were indicative of cytopathic virus-induced changes (Figure 1A3 and 1A4). Fibroblastic foci consisting of loose organizing connective tissue reflective of alveolar duct fibrosis were seen (fibrotic phase) (Figure 1B1). Other findings included: pleural fibrosis (Figure 1B4), vascular injury with thrombi (Figure 1B2), and vasculitis (Figure 1B3). A main feature was the presence of numerous inflammatory cells consisting of granulocytes (CD15+) (Supplementary Figure 1A1 and 1A2), macrophages (CD68+) (Supplementary Figure 1A3 and 1A4), and T lymphocytes (CD3+) infiltrating into alveolar septa and clustering around capillary vessels (Supplementary 1B1). Immunohistochemistry showed the presence of both CD4+ and CD8+ T lymphocytes (Supplementary Figure 1B2 and 1B3). Of note, lymphocytes were CD20− indicating an absence of infiltrating B lymphocytes. Thrombi were present and immunohistochemistry showed the presence of platelet aggregates and megakaryocytes within thrombi (Supplementary Figure 1B4). Table 3. Histopathology Findings Findings Group 1, No. (%) (n = 18) Group 2, No. (%) (n = 4) Lung  Hyaline membranes 8 (44.4) 2 (50.0)  Hyperplasia of type II pneumocyte 11 (61.2) 4 (100)  Alveolar plug 8 (44.4) 4 (100)  Alveolar fibrin deposit 9 (50.0) 3 (75.0)  Hemorrhage 10 (55.6) 2 (50.0)  Inflammatory cells 13 (72.3) 4 (100)  Diffuse alveolar damage, fibrotic phase 12 (66.7) 1 (25.0)  Microthrombi 14 (77.8) 2 (50.0)  Vasculitis 8 (44.4) 4 (100)  Multinucleated giant cells 4 (22.3) 2 (50.0) Cardiac  Myocarditis 9 (50.0) 3 (75.0)  Vasculitis 5 (27.8) 3 (75.0)  Inflammatory infiltrate 13 (72.3) 3 (75.0)  Focal necrosis 6 (33.4) 2 (50.0)  Pericarditis 9 (50.0) 4 (100)  Vascular fibrosis 4 (22.3) 2 (50.0) Hepatic  Inflammatory infiltrate 8 (44.4) 3 (75.0)  Congestion 8 (44.4) 2 (50.0)  Steatosis 9 (50.0) 3 (75.0) Renal  Inflammatory infiltrate 9 (50.0) 3 (75.0)  Glomerulosclerosis 9 (50.0) 3 (75.0)  Interstitial fibrosis 9 (50.0) 4 (100) Splenic  Congested red pulp 15 (83.4) 4 (100)  Lymphoid hypoplasia 11 (61.2) 4 (100) Bone marrow  Megakaryocytes hyperplasia 0 2 (50.0)  Adipocytes 7 (38.9) 1 (25.0) Immunohistochemistry Findings. T-cell activation is modulated by dipeptidyl peptidase-4 (DPP4) [16] and thus the expression of CD26/DPP4 and CXCR3/CD183 was analyzed on lung tissues from group 2 patients (Figure 2). Numerous CD26+ cells were found in the alveolar septa (Figure 2A1–2A3) with intense staining seen in the type II pneumocytes (Figure 2A3). Positive cells entrapped with fibrin clots in the vascular lumen were also observed (Figure 2A4). CXCR3 immunostaining showed lymphocytes localized in inflammatory perivascular aggregates (Figure 2B1, 2B2, and 2B4) which spread into alveolar septa and alveolar spaces (Figure 2B2 and 2B3). Figure 2. Immunohistological characterization of lung tissue. A1–A4, CD26/dipeptidyl peptidase-4 expression in lung tissue. Numerous strongly positive CD26+ cells are seen in the alveolar septa. A3, Intense staining is seen in the type II pneumocytes (arrows). A4, Positive cells are also seen entrapped with fibrin in the vascular lumen. B1–B4, CXCR3/CD183 immunostaining shows intense staining of lymphocytes localized in the inflammatory perivascular aggregates and spread into alveolar septa and alveolar spaces. Scale bars: A1 and B1, 100 µm; A2, A3, and B4, 7 µm; A4, B2, and B3, 14 µm. Electron Microscopic Findings. SARS-CoV-2 particles were detected within type II pneumocytes, which showed degenerating features characterized by fine and uniformly dispersed chromatin. These pneumocytes displayed swollen mitochondrial profiles and dilated rough endoplasmic reticulum (Figure 3). Numerous virus-containing compartments (VCC) of different sizes and shapes were detected (Figure 3A, 3B, and 3D). Interestingly, spherules, very small vesicles containing single viral particles (Figure 3B and 3C), were also observed. Figure 3. SARS-CoV-2 detection in lung tissue by transmission electron microscopy. A, SARS-CoV-2 particles are visible in virus-containing compartments in type II pneumocytes (arrows). B–D, Numerous viral particles are enclosed in single-membrane vacuoles (arrow). Other, very small vesicles contain single viral particles (arrowheads). Scale bars: A, 1 µm; B–D, 200nm.