ABSTRACT
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.
Competing Interest Statement
The authors have declared no competing interest.