Single‐cell RNA analysis on ACE2 expression provides insights into SARS‐CoV‐2 potential entry into the bloodstream and heart injury

Guo, Jieyu; Wei, Xiangxiang; Li, Qinhan; Li, Liliang; Yang, Zhaohua; Shi, Yu; Qin, Yue; Zhang, Xinyue; Wang, Xinhong; Zhi, Xiuling; Meng, Dan

Coronavirus disease‐2019 (COVID‐19) is a global pandemic with high infectivity and pathogenicity, accounting for tens of thousands of deaths worldwide. Recent studies have found that the pathogen of COVID‐19, severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), shares the same cell receptor angiotensin converting enzyme II (ACE2) as SARS‐CoV. The pathological investigation of COVID‐19 deaths showed that the lungs had characteristics of pulmonary fibrosis. However, how SARS‐CoV‐2 spreads from the lungs to other organs has not yet been determined. Here, we performed an unbiased evaluation of cell‐type‐specific expression of ACE2 in healthy and fibrotic lungs, as well as in normal and failed adult human hearts, using published single‐cell RNA‐seq data. We found that ACE2 expression in fibrotic lungs mainly locates in arterial vascular cells, which might provide a route for bloodstream spreading of SARS‐CoV‐2. Failed human hearts have a higher percentage of ACE2‐expressing cardiomyocytes, and SARS‐CoV‐2 might attack cardiomyocytes through the bloodstream in patients with heart failure. Moreover, ACE2 was highly expressed in cells infected by respiratory syncytial virus or Middle East respiratory syndrome coronavirus and in mice treated by lipopolysaccharide. Our findings indicate that patients with pulmonary fibrosis, heart failure, and virus infection have a higher risk and are more susceptible to SARS‐CoV‐2 infection. The SARS‐CoV‐2 might attack other organs by getting into the bloodstream. This study provides new insights into SARS‐CoV‐2 blood entry and heart injury and might propose a therapeutic strategy to prevent patients from developing severe complications.