Is the "Asian" Male an Endangered Species?

biorxiv |  We also noticed that the only Asian donor (male) has a much higher ACE2-expressing cell ratio than white and African American donors (2.50% vs. 0.47% of all cells). This might explain the observation that the new Coronavirus pandemic and previous SARS-Cov pandemic are concentrated in the Asian area.  (damn homie, are you PHUKKED?!?!?!?!)

A novel coronavirus (2019-nCov) was identified in Wuhan, Hubei Province, China in December of 2019. This new coronavirus has resulted in thousands of cases of lethal disease in China, with additional patients being identified in a rapidly growing number internationally. 2019-nCov was reported to share the same receptor, Angiotensin-converting enzyme 2 (ACE2), with SARS-Cov. Here based on the public database and the state-of-the-art single-cell RNA-Seq technique, we analyzed the ACE2 RNA expression profile in the normal human lungs. The result indicates that the ACE2 virus receptor expression is concentrated in a small population of type II alveolar cells (AT2). Surprisingly, we found that this population of ACE2-expressing AT2 also highly expressed many other genes that positively regulating viral reproduction and transmission. A comparison between eight individual samples demonstrated that the Asian male one has an extremely large number of ACE2-expressing cells in the lung. This study provides a biological background for the epidemic investigation of the 2019-nCov infection disease, and could be informative for future anti-ACE2 therapeutic strategy development.

Severe infection by 2019-nCov could result in acute respiratory distress syndrome (ARDS) and sepsis, causing death in approximately 15% of infected individuals^1,2. Once contacted with the human airway, the spike proteins of this virus can associate with the surface receptors of sensitive cells, which mediated the entrance of the virus into target cells for further replication. Recently, Xu et.al., modeled the spike protein to identify the receptor for 2019-nCov, and indicated that Angiotensin-converting enzyme 2 (ACE2) could be the receptor for this virus³. ACE2 is previously known as the receptor for SARS-Cov and NL63^4–6. According to their modeling, although the binding strength between 2019-nCov and ACE2 is weaker than that between SARS-Cov and ACE2, it is still much higher than the threshold required for virus infection. Zhou et. al. conducted virus infectivity studies and showed that ACE2 is essential for 2019-nCov to enter HeLa cells⁷. These data indicated that ACE2 is likely to be the receptor for 2019-nCov.

The expression and distribution of the receptor decide the route of virus infection and the route of infection has a major implication for understanding the pathogenesis and designing therapeutic strategies. Previous studies have investigated the RNA expression of ACE2 in 72 human tissues⁸. However, the lung is a complex organ with multiple types of cells, and such real-time PCR RNA profiling is based on bulk tissue analysis with no way to elucidate the ACE2 expression in each type of cell in the human lung. The ACE2 protein level is also investigated by immunostaining in lung and other organs^8,9. These studies showed that in normal human lung, ACE2 is mainly expressed by type II and type I alveolar epithelial cells. Endothelial cells were also reported to be ACE2 positive. However, immunostaining analysis is known for its lack of signal specificity, and accurate quantification is also another challenge for such analysis.

The recently developed single-cell RNA sequencing (scRNA-Seq) technology enables us to study the ACE2 expression in each cell type and give quantitative information at single-cell resolution. Previous work has built up the online database for scRNA-Seq analysis of 8 normal human lung transplant donors¹⁰. In current work, we used the updated bioinformatics tools to analyze the data. In total, we analyzed 43,134 cells derived from normal lung tissue of 8 adult donors. We performed unsupervised graph-based clustering (Seurat version 2.3.4) and for each individual, we identified 8~11 transcriptionally distinct cell clusters based on their marker gene expression profile. Typically the clusters include type II alveolar cells (AT2), type I alveolar cells (AT1), airway epithelial cells (ciliated cells and Club cells), fibroblasts, endothelial cells and various types of immune cells. The cell cluster map of a representative donor (Asian male, 55-year-old) was visualized using t-distributed stochastic neighbor embedding (tSNE) as shown in Fig. 1b and his major cell type marker expressions were demonstrated in Fig.2.  Fist tap Dale.