The scRNA-seq Expression Profiling of the Receptor ACE2 and the Cellular Protease TMPRSS2 Reveals Human Organs Susceptible to SARS-CoV-2 Infection

Abstract

COVID-19 patients always develop multiple organ dysfunction syndromes other than lungs, suggesting the novel virus SARS-CoV-2 also invades other organs. Therefore, studying the viral susceptibility of other organs is important for a deeper understanding of viral pathogenesis. Angiotensin-converting enzyme II (ACE2) is the receptor protein of SARS-CoV-2, and TMPRSS2 promotes virus proliferation and transmission. We investigated the ACE2 and TMPRSS2 expression levels of cell types from 31 organs to evaluate the risk of viral infection using single-cell RNA sequencing (scRNA-seq) data. For the first time, we found that the gall bladder and fallopian tube are vulnerable to SARS-CoV-2 infection. Besides, the nose, heart, small intestine, large intestine, esophagus, brain, testis, and kidney are also identified to be high-risk organs with high expression levels of ACE2 and TMPRSS2. Moreover, the susceptible organs are grouped into three risk levels based on the ACE2 and TMPRSS2 expression. As a result, the respiratory system, digestive system, and urinary system are at the top-risk level for SARS-CoV-2 infection. This study provides evidence for SARS-CoV-2 infection in the human nervous system, digestive system, reproductive system, respiratory system, circulatory system, and urinary system using scRNA-seq data, which helps in the clinical diagnosis and treatment of patients.

The Effects of COVID-19 on the Placenta During Pregnancy

“…Several studies have employed single cell RNA sequencing (scRNA-seq) to gain an understanding of the molecular features of SARS-CoV-2 infection (90)(91)(92)(93)(94). In a study by expression.…”

SARS-CoV-2 Infects Hamster Testes

“…SARS-CoV-2 has been shown to enter cells through one of two pathways, which require, in addition to its receptor angiotensin-converting enzyme 2 (ACE2), either cathepsins or transmembrane protease serine 2 (TMPRSS2) to efficiently complete its entry step [ 30 , 31 , 32 , 33 ]. Qi and colleagues analyzed expression of ACE2 and TMPRSS2 and found that cell types in the testes that express both proteins include spermatogonia, spermatogonia stem cells, peritubular myoid cells, and testes somatic cells [ 34 ]. Another study by Wang and colleagues found that ACE2 and TMPRSS2 are co-expressed in many cell types in the testes, including spermatogonia, spermatocytes, spermatids, somatic, Leydig, and Sertoli cells.…”

“…Studies analyzing the levels of ACE2, TMPRSS2, and cathepsins suggest that the testes are potentially vulnerable to SARS-CoV-2 [ 25 , 34 , 37 , 38 ]. However, it is unknown whether SARS-CoV-2 can replicate and complete its life cycle in testicular cells.…”

Ovarian Granulosa Cells From Women With Pcos Express Low Levels of Sars-Cov-2 Receptors and Co-Factors

“…ACE2 and TMPRSS2 [10]. There are reports confirming the presence of ACE2 expression at ovary, uterus, vagina and placenta [9, 11–14]. In addition to this, expression of other receptors and proteases (BSG, CTSL, FURIN) has been demonstrated in male and female reproductive tissue by several studies by using single cell RNA sequencing approach and by analyzing publically available microarray datasets [4, 15].…”

“…Apart from lungs, COVID-19 has been reported to affect human heart, liver, kidney and nervous system as well [8]. Multi-organ map for expression of SCARFs has been dissected [9]. Theoretically, SARS-CoV-2 may infect any cell or tissue type that co-expresses receptor and proteases, i.e.…”