Age-determined expression of priming protease TMPRSS2 and localization of SARS-CoV-2 in lung epithelium.

Schuler, Bryce A; Habermann, A Christian; Plosa, Erin J; Taylor, Chase J; Jetter, Christopher; Negretti, Nicholas M; Kapp, Meghan E; Benjamin, John T; Gulleman, Peter; Nichols, David S; Braunstein, Lior Z; Hackett, Alice; Koval, Michael; Guttentag, Susan H; Blackwell, Timothy S; Webber, Steven A; Banovich, Nicholas E; Kropski, Jonathan A; Sucre, Jennifer M S

The SARS-CoV-2 novel coronavirus global pandemic (COVID-19) has led to millions of cases and hundreds of thousands of deaths globally. While older adults appear at high risk for severe disease, hospitalizations and deaths due to SARS-CoV-2 among children have been relatively rare. Integrating single-cell RNA sequencing (scRNA-seq) of developing mouse lung with temporally-resolved immunofluorescence in mouse and human lung tissue, we found expression of SARS-CoV-2 Spike protein primer TMPRSS2 was highest in ciliated cells and type I alveolar epithelial cells (AT1), and TMPRSS2 expression increased with aging in mice and humans. Analysis of autopsy tissue from fatal COVID-19 cases detected SARS-CoV-2 RNA most frequently in ciliated and secretory cells in airway epithelium and AT1 cells in peripheral lung. SARS-CoV-2 RNA was highly colocalized in cells expressing TMPRSS2. Together, these data demonstrate the cellular spectrum infected by SARS-CoV-2 in lung epithelium and suggest that developmental regulation of TMPRSS2 may underlie the relative protection of infants and children from severe respiratory illness.