Systemic analysis of tissue cells potentially vulnerable to SARS-CoV-2 infection by the protein-proofed single-cell RNA profiling of ACE2, TMPRSS2 and Furin proteases

Lulin Zhou; Zubiao Niu; Xiaoyi Jiang; Zhengrong Zhang; You Zheng; Zhongyi Wang; Yichao Zhu; Lihua Gao; Xiaoning Wang; Qiang Sun

Third, the feasible routes whereby viruses get access to their target cells are also accountable for clinical manifestations. In theory, there are two major routes for virus transmission: 1) directly entering the luminal tracks via open entries of the body. The potentially affected tissues/organs include those from the respiratory system, digestive system and urinary tract, among which the respiratory system is much easier than the rest two to be infected as it's almost a completely open system while the rest two are gated by multiple ways. This may explain the prominent symptoms in respiratory system but not in the digestive and urinary systems despite high level of co-expression of ACE2, TMPRSS2 and Furin in epithelial cells lining along the tracts of the later two systems; 2) transmitting via blood stream to the entire body. This may theoretically affect all the internal organs with stromal cells expressing ACE2, with exception for those polarized cells in which the ACE2 protein is only expressed in the apical surface unreachable by the viruses from viremia. The target tissue cells affected by this route may include cardiomyocytes, stromal cells in adrenal gland, Leydig cells in testis, and stromal cells in ovary and thyroid gland. Among them, only the former two, but not the later three, are more likely the true or susceptible targets of SARS-CoV-2 when considering the co-expression of helping proteases with ACE2. It should be noted that the precondition for this route is viremia, which, however to our best knowledge, was not clearly documented in COVID-19 patients up to date. Nevertheless, frequent heart injuries in COVID-19 patients [1, 48] are consistent with the presence of occasional viremia. Under such circumstances, adrenal gland may be another vulnerable target of SARS-CoV-2, which, to our best knowledge, is identified for the first time in this study.