Age-determined expression of priming protease TMPRSS2 and localization of SARS-CoV-2 in lung epithelium
Bryce A. Schuler, … , Jonathan A. Kropski, Jennifer M.S. Sucre
Bryce A. Schuler, … , Jonathan A. Kropski, Jennifer M.S. Sucre
Published November 12, 2020
Citation Information: J Clin Invest. 2021;131(1):e140766. https://doi.org/10.1172/JCI140766.
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Concise Communication Pulmonology

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

Abstract

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.

Authors

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 M.S. Sucre

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Figure 4

Spatial localization of SARS-CoV-2 RNA in lung autopsy tissue from fatal COVID-19.

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Spatial localization of SARS-CoV-2 RNA in lung autopsy tissue from fatal...
(A) RNA-ISH of SARS-CoV-2 RNA (red) with epithelial markers SCGB1A1 (secretory cells, cyan), FOXJ1 (ciliated cells, white), SFTPC (AT2 cells, green), AGER (AT1 cells, white). Scale bars: 100 μm. (B) Quantification of cells containing SARS-CoV-2 RNA by epithelial subtype as determined by percentage of cellular area covered by SARS-CoV-2 probe in all cells positive for the epithelial marker; more than 150 cells were counted for each subtype. All data points are shown with mean ± SD. (C) RNA-ISH of large airway from the same patient demonstrating RNA transcripts for TMPRSS2 (white) in the same cells containing SARS-CoV-2 RNA (red), with secretory cells labeled in green (SCGB1A1) for context. Scale bars: 100 μm. (D) Quantification of TMPRSS2 expression in SARS-CoV-2+ cells; more than 1000 cells were counted from the 3 subjects, P < 0.05. All percentages are shown in graphs with mean ± SD. (E) RNA-ISH of SARS-CoV-2 (red) with protein immunofluorescence for TMPRSS2 protein (white). Scale bars: 100 μm.