COVID-19 is the current pandemic caused by severe acute respiratory syndrome virus 2 (SARS-CoV-2) that uses ACE2 protein on the cell surface. By analyzing publicly available datasets, I uncovered that alveolar early progenitors (AEP), a subset of the type-2 pneumocytes, showed increased ACE2 expression in the older lungs. AEPs co-express TMPRSS2, CTSL. Aged AEP-gene expression signature suggested an active response to beta-amyloid-induced ACE2 shedding, to limit the intercellular beta-amyloid accumulation in otherwise healthy human lungs. Susceptibility of AEP to SARS-CoV2 and ACE2 secretory capacity of these cells makes aged human lung sensitive for rapid-infection, by a possible in-solution ACE2 binding and entry into ACE2-negative cells, thereby increasing the target cell diversity and numbers. Single-cell analysis of COVID19 patients with moderate and severe infections, clearly showed that severe infections showed SARS-CoV-2 transcript in ACE2-negative TMPRSS-negative but CTSL-positive cell types in their bronchoalveolar lavage fluid, validating in-solution ACE2-binding enabling infection.

中文翻译：

---

老年人肺中的肺泡早期祖细胞增加了ACE2的表达，并伴有与β-淀粉样蛋白清除有关的基因：SARS-CoV-2的指示也使用老年肺中的可溶性ACE2进入ACE2阴性细胞

COVID-19是由严重急性呼吸道综合症病毒2（SARS-CoV-2）引起的当前大流行病，这种病毒在细胞表面使用ACE2蛋白。通过分析公开的数据集，我发现肺泡早期祖细胞（AEP）是2型肺细胞的一个子集，在较老的肺中显示ACE2表达增加。AEP共表达TMPRSS2，CTSL。老化的AEP基因表达特征提示对β淀粉样蛋白诱导的ACE2脱落具有积极反应，从而限制了健康人肺中细胞间β淀粉样蛋白的积累。AEP对这些细胞的SARS-CoV2和ACE2分泌能力的敏感性使老年人的肺部对快速感染敏感，这可能是由于溶液中ACE2结合并进入ACE2阴性细胞，从而增加了靶细胞的多样性和数量。