On January 9, Beijing time, the top academic journal “cell” published online a research jointly completed by researchers from school of life sciences of Xihu University and Union Hospital Affiliated to Tongji Medical College of Huazhong University of science and technology, entitled “multi organ proteomic landscape of cowid-19 autopsies”. The report reported a novel coronavirus pneumonia in the early 2020, which was used for the detection of protein molecular pathology in patients with new crown pneumonia. It helps to understand the mechanism of new crown death and to provide precise intervention for patients.
This is the first time in the world to analyze in detail and systematically the response of several key organs to the infection of new coronavirus at the protein molecular level, which provides clues and basis for clinical workers and researchers to formulate treatment plans and develop new drugs and treatment methods.
Guo Tiannan, a distinguished researcher of Xihu University, Hu Yu, Xia Jiahong, a professor of Wuhan Union Medical College Hospital, and Zhu Yi, an associate researcher of Xihu University, are the co corresponding authors of this paper. Professor Nie Xiu of Wuhan Union Medical College Hospital, doctoral students Qian Liujia and sun Rui of Guo Tiannan research group, Huang Bo and Dong Xiaochuan of Union Medical College Hospital, Xiao Qi, research assistant of Guo Tiannan research group, and Zhang Qiushi of Xihu OMI (Hangzhou) Biotechnology Co., Ltd. are co first authors.
Guo Tiannan laboratory said that this study is equivalent to the research team magnifying the changes of cells and tissues of human body infected with the new crown under the microscope by tens of thousands of times, reaching the protein molecular level, and “seeing” clearly which molecular changes lead to the pathological changes and exhaustion of human organs.
According to the paper, the research team collected 144 tissue samples from 7 organs including lung, spleen, liver, heart, kidney, thyroid and testis of 19 patients who died of covid-19. Novel coronavirus pneumonia or respiratory failure were found in all 19 COVID-19 patients, of whom 7 were complicated by advanced multiple organ dysfunction syndrome (MODS). They also collected 74 control tissue samples from 56 non-covid-19 patients.
Through microscopic pathological examination, the research team found diffuse alveolar injury, pulmonary fibrosis, neutrophil infiltration, thrombosis and other pathological changes in the lung, atrophy of the white pulp of the spleen, fatty metaplasia of the liver and infarction in some cases, cardiac muscle edema and interstitial lymphocyte infiltration in the heart, and acute renal tubular injury in the kidney.
Based on high-pressure circulation technology (PCT) and TMT labeling combined with mass spectrometry data sampling and proteomics data analysis, the research team identified a total of 11394 individual protein molecules, and drew a panoramic picture of multiple organ protein molecules of critically ill patients in Xinguan. Compared with the control tissue samples of non new crown patients, 5336 proteins in the sample group of dead patients were changed.
Among the seven organs and tissues mentioned above, the research team did not identify significantly changed proteins in the red pulp of the spleen, while the number of changed proteins in the liver was the largest (n = 1970). The team believes that novel coronavirus pneumonia patients may suffer from liver damage.
It is worth mentioning that in the process of new coronavirus invading human body, ACE2 (ACE2 protein, a protein regulating blood pressure in human body) is the receptor that binds to the invading “key” spike protein. In this molecular study, the team found that there was no significant difference in the number of ACE2 protein between new crown patients and non new crown patients. However, another protein, cathepsin L (CTSL), which helps the virus enter the cells, is significantly increased in the lungs of new crown patients.
It is suggested that the expression level of ACE2 is not changed in patients with new coronavirus death. It is only a channel for new coronavirus to enter human body, but CTSL may be a potential therapeutic target to block virus invasion.
The research team further conducted a systematic comparative study on the physiological function, pathological morphology and proteomics of various organs, and found that a number of lung proteins changed, including proteins related to virus proliferation, involved in the pathological process of pulmonary fibrosis and degradation of virus limiting factors. At the same time, proteomics showed that the lung and spleen showed adaptive immune response inhibition characterized by up regulation of immune checkpoint protein and down regulation of T cell rich protein, which was also confirmed by the decrease of T, B and other lymphocytes in spleen.
In addition, although from the clinical pathology point of view, only the lung had substantial fibrosis, but the proteomic results showed that liver, kidney and other organs also had the precursor of tissue fibrosis. This suggests that for the critically ill patients who have recovered, it is necessary to prevent and take early intervention for the possible sequela of “multiple organ fibrosis”.
It is worth mentioning that in this pandemic, the male infection and mortality are higher, and the new coronavirus damages the male reproductive function. Guo Tiannan et al. Also found 10 proteins that had significant changes in the testicular tissue of patients with new crowns. Their functions were closely related to the inhibition of cholesterol synthesis, the decrease of sperm activity and the decrease of Leydig cell specific markers. Leydig cells are closely related to the synthesis and secretion of male androgen, suggesting that the fertility of male patients with new crown may be affected.
The research team also reminded the limitations of these studies. These studies are based on tissue samples of patients with new crown death. However, whether the same changes will occur in mild and severe patients and whether such changes are reversible still need further study.