Protein Cell: Chen Jiekai/Deng Xilong/Chen Xinwen collaboration reveals the cellular mechanism of acute respiratory distress caused by the new crown virus infection.

!---- new coronavirus poses a serious threat to human life and health, causing more than 13 million people worldwide to become infected and more than 570,000 deadThe lungs are the main organ of the new crown virus infection, and the direct cause of death in most new coronal patients (COVID-19) is acute respiratory distress (ARDS) due to respiratory failureARDS is the main disease of patients with new coronary critical conditions, and the course of the disease is extremely long, resulting in a sharp depletion of the resources of the intensive care unit (ICU), so the study of the pathological mechanism of the new crown critical condition is of great significance for the effective response to the outbreakChen Jiekai Researcher, Guangzhou Institute of Biomedicine and Health Research- Biological Island Laboratory of the Chinese Academy of Sciences, Director of The Department of Critical Medicine of Guangzhou Eighth People's Hospital, Deng Xilong, And Chen Xinwen, Researcher of Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, in Cooperation with Protein The article "Single-cell analysis sphinsbronchoveolar epithelial dysfunction in COVID-19 patients" published in Cell published in the journal "Single-cell analysis of bronchoalveolar epithelial dysfunction in COVID-19 patients" reveals the pathological changes in the oral epithelial cells of the new crown patients through single-cell transcriptomy irrigation lotion (scRNA-seq), revealing pathological changes in the secretion of excessive mucus and mucus removal abnormalities under the new crown pathology conditions, and providing important treatment mechanisms for understanding the long-term critical conditions of the new crownThe lungs are mainly composed of millions of alveoli, alveoli is the basic breathing unit, its surface attached to a large number of capillaries, the body through capillaries and alveoli membrane to complete gas exchange, different alveoli between the bronchial tubes connected to each other, and finally connect the trachea to the mouth / nose, this is the complete breathing pipeClinical testing and autopsy results show that the lungs of patients with severe new crowns produce a large amount of very poor lysy fluid, these mucus will block the bronchial tubes and even alveoli, so that normal respiratory gas exchange is blocked, is one of the important causes of the new coronary disease ARDSUnder normal physiological conditions, bronchial mucus secretion is beneficial to the human body, they can absorb the dust, pathogens and other harmful substances in the air we breathe in, and at the same time with the help of cilia cells (through cilia swing) to clean the mucus out of the body (i.esputum)However, in pathological cases, excessive mucus secretion can cause blocking of the trachea, affect normal breathing, and promote inflammation, aggravate viral infection and lung damageAt present, the mechanism of the production and blocking of the small airways of the mucus in the patients with the new crown is not clear, so it will be important for clinical treatment to understand the sources and causes of mucus produced by the patients with the new crownBased on these key issues, the team compared pathological changes in patients with new coronary critical diseases compared to lung cells in healthy humans through scRNA-seqThe analysis found that the Gel-forming mucoprotein-related genes MUC5AC and MUC5B in the mucoprotein family were significantly highly expressed in patients, and were mainly derived from an epithelial cell called Club, indicating that the mucus in the new corona patient siber mainly came from lung club cellsIn addition to mucoproteins, the Trefoil factor TFF3 and the transglutamine enzyme TG2 also increased significantly, all of which promote the cross-linking and covalent bond formation of mucoproteins to each other, and improve mucus viscosityThe researchers also found that after infection, expression of genes that regulate cilia production and structures such as FOXJ1, RFX3, IFT27, DNAI2 decreased significantly, while the expression of ATP hezyns earlier increased significantly, with previous studies showing that ATP stimulation can lead to mucus secretion increases thousands of timesThe above results show that the virus infection causes the club cell mucus over-secretion, and the ciliostobrium activity decreases, this series of epithelial cell regulation disorder seisizer causes the secretion of excessive mucus in the lungs over-accumulation, until finally blocked the small airways inside the lungs, leading to respiratory failureOn the mechanism, the researchers found that after a viral infection, alveolar macrophages secrete cytokine CCL2, which may recruit mononucleic/central granulocytes into infected areas to be activated; It is worth noting that a retrospective study published in the international medical journal Lancet Rheumatol during the review period found that 72% of patients with THE treatment of IL-1 beta antagonists with COVID-19 patients had significantly improved their conditionIt is reported that the Chinese Academy of Sciences Guangzhou Institute of Biomedicine and Health - Biological Island Laboratory Chen Jiekai researcher, Guangzhou Eighth People's Hospital Department of Critical Medicine Deng Xilong Director, Chinese Academy of Sciences Guangzhou Institute of Biomedicine and Health Chen Xinwen researcher as co-authors Biological Island Laboratory Dr He Jiangping, Cai Baomei, Guangzhou Eighth People's Hospital Cai Shuijiang, Chinese Academy of Sciences Guangzhou Institute of Biomedicine and Health Feng Huijian, Lin Lihui as co-first authors, the research by Guangzhou Medical University Respiratory Disease National Key Laboratory Zhao Jinxuan researcher's strong assistance, and in the course of the research by The guidance of Zhong Nanshan academician