• Chaofu Wang, Jing Xie, Lei Zhao, Xiaochun Fei, Heng Zhang, Yun Tan, Xiu Nie, Luting Zhou, Zhenhua Liu, Yong Ren, Ling Yuan, Yu Zhang, Jinsheng Zhang, Liwei Liang, Xinwei Chen, Xin Liu, Peng Wang, Xiao Han, Xiangqin Weng, Ying Chen, Ting Yu, Xinxin Zhang, Jun Cai, Rong Chen, Zheng-Li Shi, and Xiu-Wu Bian.
• Department of Pathology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China. Electronic address: wangchaofu@126.com.
• EBioMedicine. 2020 Jul 1; 57: 102833.

BackgroundThe novel coronavirus pneumonia COVID-19 caused by SARS-CoV-2 infection could lead to a series of clinical symptoms and severe illnesses, including acute respiratory distress syndrome (ARDS) and fatal organ failure. We report the fundamental pathological investigation in the lungs and other organs of fatal cases for the mechanistic understanding of severe COVID-19 and the development of specific therapy in these cases.MethodsThe autopsy and pathological investigations of specimens were performed on bodies of two deceased cases with COVID-19. Gross anatomy and histological investigation by Hematoxylin and eosin (HE) stained were reviewed on each patient. Alcian blue/periodic acid-Schiff (AB-PAS) staining and Masson staining were performed for the examinations of mucus, fibrin and collagen fiber in lung tissues. Immunohistochemical staining was performed on the slides of lung tissues from two patients. Real-time PCR was performed to detect the infection of SARS-CoV-2. Flow cytometry analyses were performed to detect the direct binding of S protein and the expression of ACE2 on the cell surface of macrophages.FindingsThe main pathological features in lungs included extensive impairment of type I alveolar epithelial cells and atypical hyperplasia of type II alveolar cells, with formation of hyaline membrane, focal hemorrhage, exudation and pulmonary edema, and pulmonary consolidation. The mucous plug with fibrinous exudate in the alveoli and the dysfunction of alveolar macrophages were characteristic abnormalities. The type II alveolar epithelial cells and macrophages in alveoli and pulmonary hilum lymphoid tissue were infected by SARS-CoV-2. S protein of SARS-CoV-2 directly bound to the macrophage via the S-protein-ACE2 interaction.InterpretationInfection of alveolar macrophage by SARS-CoV-2 might be drivers of the "cytokine storm", which might result in damages in pulmonary tissues, heart and lung, and lead to the failure of multiple organs .FundingShanghai Guangci Translational Medical Research Development Foundation, Shanghai, China.Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.

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