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

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.

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View Supplemental Table 1: Single-cell gene expression matrix of select genes in the lung the lung epithelium. Lungs were collected from mice at multiple developmental timepoints (E18, P0, P7, P14, and P64) and separated into single-cell suspensions followed by enrichment for viable cells that were CD45 and Ter119 negative. Cells were given individual barcodes and sequenced as described in the supplemental methods. The expression pattern of marker genes was used to select epithelial cells and determine cell type. Sequencing results of select genes are represented as normalized counts that have been corrected for the presence of ambient RNA using SoupX. Each row represents the results from an individual cell.