The scRNA-seq expression profiling of the receptor ACE2 and the cellular protease TMPRSS2 reveals human organs susceptible to COVID-19 infection

Jing Qi; Yang Zhou; Jiao Hua; Liying Zhang; Jialin Bian; Beibei Liu; Zicen Zhao; Shuilin Jin

The advantage of scRNA-seq over bulk RNA sequence is the identification of cell types by clustering the gene expression of cells. To explore the potentially susceptible organs, previous studies analyzed the ACE2 expression of some human organs using scRNA-seq data. The gross anatomical observation indicates that the lesions caused by the novel coronavirus are mainly in the lung. 13 ACE2 is mainly expressed in type II alveolar cells (AT2) in the lung, 14 which implies AT2 cell is the cell type vulnerable to COVID-19 infection. Many researchers have obtained the susceptibility of other organs from different system using ACE2 expression in AT2 cells as a reference. Following this way, many respiratory organs were considered, and ACE2 was reported to be highly expressed in the nasal tissue, mouth, airway, and lung. [15] [16] [17] The esophagus, large intestine (ileum and colon), and pancreas were identified as high-risk organs in the digestive system by the following papers. [16] [17] [18] [19] The kidney and bladder as major organs of urinary system were also indicated to be high ACE2-expressed. 17, 20, 21 Besides, the testes and uterus were manifested to be susceptible organs, implying that the reproductive system was a potential route of viral infection. 22, 23 In this paper, the expression level of ACE2 and TMPRSS2 in different cell clusters of organs from nine major systems (including the respiratory system, digestive system, nervous system, endocrine system, reproductive system, circulatory system, urinary system, and motor systems) were obtained using the scRNA-seq data. For the first time, we found the brain (substantia nigra and cortex), fallopian tube, and gall bladder are vulnerable to COVID-19 infection; Besides, the lung, nose (nasal brushing epithelial cells, nasal turbinate epithelial cells, and nasal airway epithelial cells), heart, small intestine (jejunum, ileum, and duodenum), large intestine (rectum and colon), esophagus, testes, and kidney are predicted as high-risk organs under a more rigorous standard; Moreover, as the spike (S) protein initiated by TMPRSS2 is essential for the entry of the virus into the target cells and the transmission of the virus in the infected host, we used the expression level of TMPRSS2 to predict the risk level of each susceptible organ, and found that the respiratory system, digestive system, and reproductive system are the top level vulnerable to COVID-19 infection.