Clinicopathologic and Immunohistochemical Findings from Autopsy of Patient with COVID-19, Japan

Abstract

An autopsy of a patient in Japan with coronavirus disease indicated pneumonia lung pathology, manifested as diffuse alveolar damage. We detected severe acute respiratory syndrome coronavirus 2 antigen in alveolar epithelial cells and macrophages. Coronavirus disease is essentially a lower respiratory tract disease characterized by direct viral injury of alveolar epithelial cells.

Keywords: COVID-19; Japan; SARS-CoV-2; autopsy; coronavirus disease; cruise; diffuse alveolar damage; electron microscopy; immunohistochemistry; next-generation sequencing; respiratory infections; severe acute respiratory syndrome coronavirus 2; viruses; zoonoses.

Figure 1

Chest radiograph and computed tomography results from an 84-year-old woman who died from coronavirus disease, Toshima Hospital, Tokyo, Japan, February 2020. A) Chest radiographs taken on admission (illness day 8), showing reticular shadows, mainly in bilateral lower lung fields. B, C) Chest computed tomography scan taken on illness day 8, indicating ground-glass opacities mainly located in posterior segments of the bilateral lower lobes, where the highest numbers of viral RNA copies were found on autopsy. D) Chest radiographs taken on illness day 14, with shadows spreading to almost entire lungs and exhibiting air bronchograms.

Figure 2

Pathologic findings for the lungs, lymph nodes, and kidneys in an autopsy of an 84-year-old woman who died from coronavirus disease, Toshima Hospital, Tokyo, Japan, February 2020. A) Marked diffuse alveolar damage in exudative phase with prominent hyaline membrane formation in lung tissues. Hematoxylin & eosin (H&E) staining. Scale bar indicates 200 µm. B, C) Desquamation and squamous metaplasia of the epithelium (B) and organized hyaline membranes (C), with septal fibrosis in the organizing phase lesions in lung sections. H&E staining. Scale bar indicates 200 µm. D) Inflammatory infiltrate comprised predominately of plasma cells in the alveolar septa. H&E staining. Scale bar indicates 50 µm. E) Obvious erythrophagocytic macrophages in the lymph nodes. H&E staining. Scale bar indicates 20 µm. F) Numerous microthrombi in the glomerulus in the kidneys. H&E staining. Scale bar indicates 100 µm. G) Immunostaining (brown) of severe acute respiratory syndrome coronavirus 2 antigen in alveolar epithelial cells. Scale bar indicates 50 µm. Inset: multinucleated syncytial cells; scale bar indicates 20 µm. H, I) Double immunofluorescence staining for severe acute respiratory syndrome coronavirus 2 (red) with epithelial cell marker (H; epithelial membrane antigen staining, green); macrophage marker (I; anti-CD68 antibody staining, green) in the same cell. TO-PRO-3 nucleic acid staining (blue) and differential contrast images are also shown. Scale bar indicates 20 µm.