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    Neonatal hyperoxia enhances age-dependent expression of SARS-CoV-2 receptors in mice

    Authors: Min Yee; Ethan David Cohen; Jeannie Haak; Andrew M Dylag

    doi:10.1101/2020.07.22.215962 Date: 2020-07-22 Source: bioRxiv

    The severity of COVID-19 MESHD lung disease MESHD 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 MESHD because their early exposure to oxygen at birth increases their risk of being hospitalized when infected with RSV and other respiratory viruses. Our prior studies in mice showed how high levels of oxygen ( hyperoxia MESHD) between postnatal days 0-4 increases the severity of influenza A virus infections by reducing the number of alveolar epithelial type 2 MESHD ( AT2 MESHD) cells. Because AT2 MESHD cells express the SARS-CoV-2 receptors angiotensin converting enzyme (ACE2) and transmembrane protease/serine subfamily member 2 (TMPRSS2), we expected their expression would decline as AT2 MESHD cells were depleted by hyperoxia MESHD. Instead, we made the surprising discovery that expression of Ace2 and Tmprss2 mRNA increases as mice age and is accelerated by exposing mice to neonatal hyperoxia MESHD. ACE2 is primarily expressed at birth by airway Club cells and becomes detectable in AT2 MESHD cells by one year of life. Neonatal hyperoxia increases MESHD ACE2 expression in Club cells and makes it detectable in 2-month-old AT2 MESHD cells. This early and increased expression of SARS-CoV-2 receptors was not seen in adult mice who had been administered the mitochondrial superoxide scavenger mitoTEMPO during hyperoxia MESHD. Our finding that early life insults such as hyperoxia MESHD enhances the age-dependent expression of SARS-CoV-2 receptors in the respiratory epithelium helps explain why COVID-19 MESHD lung disease MESHD is greater in the elderly and people with pre-existing co-morbidities.

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MeSH Disease
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