TY - JOUR AU - Schuler, Bryce A. AU - Habermann, A. Christian AU - Plosa, Erin J. AU - Taylor, Chase J. AU - Jetter, Christopher AU - Negretti, Nicholas M. AU - Kapp, Meghan E. AU - Benjamin, John T. AU - Gulleman, Peter AU - Nichols, David S. AU - Braunstein, Lior Z. AU - Hackett, Alice AU - Koval, Michael AU - Guttentag, Susan H. AU - Blackwell, Timothy S. AU - Webber, Steven A. AU - Banovich, Nicholas E. AU - , AU - , AU - Kropski, Jonathan A. AU - Sucre, Jennifer M.S. T1 - Age-determined expression of priming protease TMPRSS2 and localization of SARS-CoV-2 in lung epithelium PY - 2021/01/04/ AB - The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) novel coronavirus 2019 (COVID-19) global pandemic has led to millions of cases and hundreds of thousands of deaths. 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 that 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. JF - The Journal of Clinical Investigation JA - J Clin Invest SN - 0021-9738 DO - 10.1172/JCI140766 VL - 131 IS - 1 UR - https://doi.org/10.1172/JCI140766 PB - The American Society for Clinical Investigation ER -