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

• Type of Material: Article
• Authors: Bryce A. Schuler, Vanderbilt University; A. Christian Habermann, Vanderbilt University; Erin J. Plosa, Vanderbilt University; Chase J. Taylor, Vanderbilt University; Christopher Jetter, Vanderbilt University; Meghan E. Kapp, Vanderbilt University; John T. Benjamin, Vanderbilt University; Peter Gulleman, Vanderbilt University; David S. Nichols, Vanderbilt University; Lior Z. Braunstein, Memorial Sloan Kettering Cancer Center; Alice Hackett, Vanderbilt University; Michael Koval, Emory University; Susan H. Guttentag, Vanderbilt University; Timothy S. Blackwell, Vanderbilt University; Steven A. Webber, Vanderbilt University; Nicholas E. Banovich, Translational Genomics Research Institute; Jonathan A. Kropski, Vanderbilt University; Jennifer M. S. Sucre, Vanderbilt University
• Language: English
• Date: 2020-05-23
• Publisher: National Institutes of Health
• Publication Version: Preprint (Prior to Peer Review)
• Copyright Statement: The copyright holder for this prepint is the author/funder
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1101/2020.05.22.111187
• Title of Journal or Parent Work: biorxiv
• Grant/Funding Information: This work was supported by NIH K08143051 (JMS), K08HL130595 (JAK), R01HL145372(JAK/NEB), P01HL092470(TSB), K08HL127102(EJP), K08HL133484(JTB), R01AI077505 (DWH), P30AI110527 (SAM), R01AI142095(SAK/SAM), TR002243. Flow Cytometry experiments were performed in the VMC Flow Cytometry Shared Resource. The VMC Flow Cytometry Shared Resource is supported by the Vanderbilt Ingram Cancer Center (P30 CA68485) and the Vanderbilt Digestive Disease Research Center(DK058404).
• Keywords: cellular infectivity; pediatric population; respiratory epithelium; symptoms; morbidity and mortality; asymptomatic carriage; healthcare systems; global pandemic; elderly; diversity of clinical phenotypes; multi-organ failure; viral attachment; SARS-CoV-2; global burden of disease; neonatal infections; biologic rationale; novel coronavirus
• Research Categories: Health Sciences, Pathology; Health Sciences, Health Care Management; Biology, Virology; Health Sciences, Medicine and Surgery; Health Sciences, Immunology

Abstract

The SARS-CoV-2 novel coronavirus global pandemic (COVID-19) has led to millions of cases and hundreds of thousands of deaths around the globe. While the elderly 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 the developing mouse lung with temporally-resolved RNA-in-situ hybridization (ISH) 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 was increased with aging in mice and humans. Analysis of autopsy tissue from fatal COVID-19 cases revealed SARS-CoV-2 RNA was detected most frequently in ciliated and secretory cells in the airway epithelium and AT1 cells in the 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 the lung epithelium, and suggest that developmental regulation of TMPRSS2 may underlie the relative protection of infants and children from severe respiratory illness.