Age-determined expression of priming protease TMPRSS2 and localization of SARS-CoV-2 in lung epithelium.
Bryce A Schuler, A Christian Habermann, Erin J Plosa, Chase J Taylor, Christopher Jetter, Nicholas M Negretti, Meghan E Kapp, John T Benjamin, Peter Gulleman, David S Nichols, Lior Z Braunstein, Alice Hackett, Michael Koval, Susan H Guttentag, Timothy S Blackwell, Steven A Webber, Nicholas E Banovich, Vanderbilt COVID-19 Consortium Cohort, Human Cell Atlas Biological Network, Jonathan A Kropski, Jennifer Ms Sucre
Author Information
Bryce A Schuler: Department of Pediatrics.
A Christian Habermann: Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, and.
Erin J Plosa: Department of Pediatrics.
Chase J Taylor: Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, and.
Christopher Jetter: Department of Pediatrics.
Nicholas M Negretti: Department of Pediatrics.
Meghan E Kapp: Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
John T Benjamin: Department of Pediatrics.
Peter Gulleman: Department of Pediatrics.
David S Nichols: Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, and.
Lior Z Braunstein: Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
Alice Hackett: Department of Pediatrics.
Michael Koval: Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Emory University, Atlanta, Georgia, USA.
Susan H Guttentag: Department of Pediatrics.
Timothy S Blackwell: Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, and.
Steven A Webber: Department of Pediatrics.
Nicholas E Banovich: Translational Genomics Research Institute, Phoenix, Arizona, USA.
Jonathan A Kropski: Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, and.
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.
