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1.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-323544

ABSTRACT

The coronavirus disease-19 (COVID-19) caused by SARS-CoV-2 infection can lead to a series of clinical settings from non-symptomatic viral carriers/spreaders to severe illness characterized by acute respiratory distress syndrome (ARDS)1,2. A sizable part of patients with COVID-19 have mild clinical symptoms at the early stage of infection, but the disease progression may become quite rapid in the later stage with ARDS as the common manifestation and followed by critical multiple organ failure, causing a high mortality rate of 7-10% in the elderly population with underlying chronic disease1-3. The pathological investigation in the lungs and other organs of fatal cases is fundamental for the mechanistic understanding of severe COVID-19 and the development of specific therapy in these cases. Gross anatomy and molecular markers allowed us to identify, in two fatal patients subject to necropsy, the main pathological features such as exudation and hemorrhage, epithelium injuries, infiltration of macrophages and fibrosis in the lungs. The mucous plug with fibrinous exudate in the alveoli and the activation of alveolar macrophages were characteristic abnormalities. These findings shed new insights into the pathogenesis of COVID-19 and justify the use of interleukin 6 (IL6) receptor antagonists and convalescent plasma with neutralizing antibodies against SARS-CoV-2 for severe patients.Authors Chaofu Wang, Jing Xie, Lei Zhao, Xiaochun Fei, Heng Zhang, and Yun Tan contributed equally to this work. Authors Chaofu Wang, Jun Cai, Rong Chen, Zhengli Shi, and Xiuwu Bian jointly supervised this work.

2.
EBioMedicine ; 57: 102833, 2020 Jul.
Article in English | MEDLINE | ID: covidwho-613483

ABSTRACT

BACKGROUND: The 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. METHODS: The 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. FINDINGS: The 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. INTERPRETATION: Infection 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 . FUNDING: Shanghai Guangci Translational Medical Research Development Foundation, Shanghai, China.


Subject(s)
Alveolar Epithelial Cells/pathology , Coronavirus Infections/pathology , Cytokine Release Syndrome/pathology , Lung/pathology , Macrophages, Alveolar/pathology , Pneumonia, Viral/pathology , Angiotensin-Converting Enzyme 2 , Autopsy , Betacoronavirus , COVID-19 , China , Coronavirus Infections/mortality , Cytokine Release Syndrome/mortality , Cytokines/blood , Cytokines/metabolism , Female , Humans , Hyperplasia/pathology , Male , Middle Aged , Pandemics , Peptidyl-Dipeptidase A/metabolism , Pneumonia, Viral/mortality , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/metabolism
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