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Age-determined expression of priming protease TMPRSS2 and localization of SARS-CoV-2 in lung epithelium.
Schuler, Bryce A; Habermann, A Christian; Plosa, Erin J; Taylor, Chase J; Jetter, Christopher; Negretti, Nicholas M; Kapp, Meghan E; Benjamin, John T; Gulleman, Peter; Nichols, David S; Braunstein, Lior Z; Hackett, Alice; Koval, Michael; Guttentag, Susan H; Blackwell, Timothy S; Webber, Steven A; Banovich, Nicholas E; Kropski, Jonathan A; Sucre, Jennifer Ms.
  • Schuler BA; Department of Pediatrics.
  • Habermann AC; Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, and.
  • Plosa EJ; Department of Pediatrics.
  • Taylor CJ; Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, and.
  • Jetter C; Department of Pediatrics.
  • Negretti NM; Department of Pediatrics.
  • Kapp ME; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
  • Benjamin JT; Department of Pediatrics.
  • Gulleman P; Department of Pediatrics.
  • Nichols DS; Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, and.
  • Braunstein LZ; Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
  • Hackett A; Department of Pediatrics.
  • Koval M; Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Emory University, Atlanta, Georgia, USA.
  • Guttentag SH; Department of Pediatrics.
  • Blackwell TS; Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, and.
  • Webber SA; Department of Cell and Developmental Biology, Vanderbilt University, Nashville, Tennessee, USA.
  • Banovich NE; Department of Veterans Affairs Medical Center, Nashville, Tennessee, USA.
J Clin Invest ; 131(1)2021 01 04.
Article in English | MEDLINE | ID: covidwho-1011053
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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Serine Endopeptidases / Gene Expression Regulation, Enzymologic / Alveolar Epithelial Cells / SARS-CoV-2 / COVID-19 Type of study: Prognostic study Limits: Adult / Animals / Child, preschool / Female / Humans / Infant / Male Language: English Year: 2021 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Serine Endopeptidases / Gene Expression Regulation, Enzymologic / Alveolar Epithelial Cells / SARS-CoV-2 / COVID-19 Type of study: Prognostic study Limits: Adult / Animals / Child, preschool / Female / Humans / Infant / Male Language: English Year: 2021 Document Type: Article