ACE2, TMPRSS2 distribution and extrapulmonary organ injury in patients with COVID-19

Abstract

At the end of 2019, the coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in China. Currently, it is breaking out globally and posing a serious threat to public health. The typically clinical characteristics of COVID-19 patients were fever and respiratory symptoms, and a proportion of patients were accompanied by extrapulmonary symptoms including cardiac injury, kidney injury, liver injury, digestive tract injury, and neurological symptoms. Angiotensin converting enzyme 2 (ACE2) has been proven to be a major receptor for SARS-CoV-2 and could mediate virus entry into cells. And transmembrane protease serine 2 (TMPRSS2) could cleave the spike (S) protein of SARS-CoV-2, which facilitates the fusion of SARS-CoV-2 and cellular membranes. The mRNA expressions of both ACE2 and TMPRSS2 were observed in the heart, digestive tract, liver, kidney, brain and other organs. SARS-CoV-2 may have a capacity to infect extrapulmonary organs due to the expressions of ACE2 and TMPRSS2 in the cells and tissues of these organs. It seems that there is a potential involvement of ACE2 and TMPRSS2 expressions in the virus infection of extrapulmonary organs and the manifestation of symptoms related to these organs in patients with COVID-19. Here, we revealed the expressions of ACE2 and TMPRSS2 in extrapulmonary organs, and we also summarized the clinical manifestation and the management of extrapulmonary complications in patients with COVID-19.

Keywords: ACE2; COVID-19; Clinical management; Extrapulmonary organs; SARS-CoV-2; TMPRSS2.

Graphical abstract

Fig. 1

Entry of SARS-CoV-2 into host cells. SARS-CoV-2 infected the host cells by the spike protein of the virus and the functions of ACE2 and TMPRSS2 in host cells.

Fig. 2

Tissue distributions of ACE2 and TMPRSS2 in human. (A–B) the schematic diagram of the expressions of ACE2 (A) and TMPRSS2 (B) in multiple human tissues. The colour strength is corresponding to the gene expression level. ACE2 and TMPRSS2 were expressed in the brain and heart; ACE2 expression is expressed at a relative low level in hepatocytes and mainly located in cholangiocytes, while TMPRSS2 is expressed in the hepatocytes and cholangiocytes; ACE2 and TMPRSS2 were highly expressed in kidney and intestinal epithelial cells. Both ACE2 and TMPRSS2 were also expressed in the esophagus, stomach, nose, testis, pancreas, breast, prostate and thyroid.