Age-related expression of SARS-CoV-2 priming protease TMPRSS2 in the developing lung

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

The emergence of the SARS-CoV-2 novel coronavirus has led to a global pandemic (COVID-19), with more than 5 million cases as of May 2020(1). Available data suggest that severe illness and death from COVID-19 are rare in the pediatric population(2). Integrating single-cell RNA sequencing of the developing mouse lung with temporally-resolved RNA-in-situ hybridization (ISH) 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 increased with aging in mice and humans. SARS-CoV-2 RNA colocalized with TMPRSS2 mRNA in lung cells from a patient who died of SARS-CoV-2. Together, these data suggest developmental regulation of TMPRSS2 may underlie the relative protection of infants and children from severe respiratory illness.