Alveolar macrophage activation and cytokine storm in the pathogenesis of severe COVID-19
Authors: Chaofu Wang, Jing Xie, Lei Zhao, Xiaochun Fei, Heng Zhang, Yun Tan, 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, Zhengli Shi, Xiuwu Bian
Date published Online: 25th March 2020
Source: Research Square
This article presents a pathological investigation of the lung, heart, kidney and lymph nodes of two fatal cases of COVID-19. In lung, exudation and haemorrhage, epithelium injuries, alveolar macrophage infiltration and fibrosis and cytokine expression were observed. A distinctive feature of COVID-19 was the presence of mucus plugs with fibrinous exudate in respiratory tracts including distal regions, which may play a role in sputum suction failure. Infected alveolar macrophages expressed ACE2 and experiments in blood of healthy patients suggested a possibility of a direct infection of macrophages and monocytes by SARS-CoV-2. Thus the authors suggest macrophages are central to the cytokine storm.
- Significant increase in alveolar macrophages, in part filling alveolar cavities. Lung macrophages showed moderate expression of IL-6 and TNF and strong expression of IL-10 and PD-L1. In comparison, lower degree of infiltration of lymphocytes was reported.
- Microscopical abnormalities observed in heart and kidney, but no viral presence in these organs.
- Type II alveolar epithelial cells, alveolar macrophages, macrophages in the pulmonary hilum lymph nodes and spleen show positive staining with SARS-CoV–2 Rp3-NP
- Other cells infected by SARS-CoV-2 include gastrointestinal mucosa cells, submucosa ganglion cells in the small intestine, and spermatogenic testicular cells.
- COVID19 lung pathology has some distinct features compared to SARS including lower presence of hyaline membrane abnormality. Instead, COVID-19 shows excessive mucus plugs and fibrinous exudation.
- SARS-CoV-2 infected alveolar macrophages expressed ACE2
Gives a nice description of the gross anatomy of the lungs of COVID19 victims and highlights similarities/differences with previous SARS virus infection. Thus, it increases understanding of the pathogenesis of COVID-19 and adds to the growing body of literature.
Strengths and weaknesses of the paper
Strengths: Good pathological description of COVID-19 pathogenesis in several organs at gross and molecular level
Weaknesses: sample size – lungs of only 2 patients examined. Also, connection between direct infection of macrophages and cytokine storm is important, but remains correlative.