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Neonatal hyperoxia enhances age-dependent expression of SARS-CoV-2 receptors in mice.
Yee, Min; David Cohen, E; Haak, Jeannie; Dylag, Andrew M; O'Reilly, Michael A.
  • Yee M; The Department of Pediatrics, School of Medicine and Dentistry, The University of Rochester, 601 Elmwood Avenue, Box 850, Rochester, NY, 14642, USA.
  • David Cohen E; The Department of Pediatrics, School of Medicine and Dentistry, The University of Rochester, 601 Elmwood Avenue, Box 850, Rochester, NY, 14642, USA.
  • Haak J; The Department of Pediatrics, School of Medicine and Dentistry, The University of Rochester, 601 Elmwood Avenue, Box 850, Rochester, NY, 14642, USA.
  • Dylag AM; The Department of Pediatrics, School of Medicine and Dentistry, The University of Rochester, 601 Elmwood Avenue, Box 850, Rochester, NY, 14642, USA.
  • O'Reilly MA; The Department of Pediatrics, School of Medicine and Dentistry, The University of Rochester, 601 Elmwood Avenue, Box 850, Rochester, NY, 14642, USA. michael_oreilly@urmc.rochester.edu.
Sci Rep ; 10(1): 22401, 2020 12 28.
Article in English | MEDLINE | ID: covidwho-997946
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ABSTRACT
The severity of COVID-19 lung disease is higher in the elderly and people with pre-existing co-morbidities. People who were born preterm may be at greater risk for COVID-19 because their early exposure to oxygen (hyperoxia) at birth increases the severity of respiratory viral infections. Hyperoxia at birth increases the severity of influenza A virus infections in adult mice by reducing the number of alveolar epithelial type 2 (AT2) cells. Since AT2 cells express the SARS-CoV-2 receptors angiotensin converting enzyme (ACE2) and transmembrane protease/serine subfamily member 2 (TMPRSS2), their expression should decline as AT2 cells are depleted by hyperoxia. Instead, ACE2 was detected in airway Club cells and endothelial cells at birth, and then AT2 cells at one year of age. Neonatal hyperoxia stimulated expression of ACE2 in Club cells and in AT2 cells by 2 months of age. It also stimulated expression of TMPRSS2 in the lung. Increased expression of SARS-CoV-2 receptors was blocked by mitoTEMPO, a mitochondrial superoxide scavenger that reduced oxidative stress and DNA damage seen in oxygen-exposed mice. Our finding that hyperoxia enhances the age-dependent expression of SARS-CoV-2 receptors in mice helps explain why COVID-19 lung disease is greater in the elderly and people with pre-existing co-morbidities.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Receptors, Virus / Serine Endopeptidases / Hyperoxia / Alveolar Epithelial Cells / Angiotensin-Converting Enzyme 2 / COVID-19 Type of study: Prognostic study Limits: Animals / Humans / Infant, Newborn Language: English Journal: Sci Rep Year: 2020 Document Type: Article Affiliation country: S41598-020-79595-2

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Receptors, Virus / Serine Endopeptidases / Hyperoxia / Alveolar Epithelial Cells / Angiotensin-Converting Enzyme 2 / COVID-19 Type of study: Prognostic study Limits: Animals / Humans / Infant, Newborn Language: English Journal: Sci Rep Year: 2020 Document Type: Article Affiliation country: S41598-020-79595-2