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《bioRxiv，6月13日，Inhaled corticosteroids downregulate the SARS-CoV-2 receptor ACE2 in COPD through suppression of type I interferon》

  • 来源专题：COVID-19科研动态监测
  • 编译者： xuwenwhlib
  • 发布时间：2020-06-14

  • Inhaled corticosteroids downregulate the SARS-CoV-2 receptor ACE2 in COPD through suppression of type I interferon

    Lydia J Finney, Nicholas Glanville, Hugo Farne, Julia Aniscenko, Peter Fenwick, Samuel Kemp, Maria-Belen Trujillo-Torralbo, Maria Calderazzo, Jadwiga A Wedzicha, Patrick Mallia, Nathan W Bartlett, Sebastian L Johnston, Aran Singanayagam

    doi: https://doi.org/10.1101/2020.06.13.149039

    Abstract

    Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 is a new rapidly spreading infectious disease. Early reports of hospitalised COVID-19 cases have shown relatively low frequency of chronic lung diseases such as chronic obstructive pulmonary disease (COPD) but increased risk of adverse outcome. The mechanisms of altered susceptibility to viral acquisition and/or severe disease in at-risk groups are poorly understood. Inhaled corticosteroids (ICS) are widely used in the treatment of COPD but the extent to which these therapies protect or expose patients with a COPD to risk of increased COVID-19 severity is unknown. Here, using a combination of human and animal in vitro and in vivo disease models, we show that ICS administration attenuates pulmonary expression of the SARS-CoV-2 viral entry receptor angiotensin-converting enzyme (ACE)-2. This effect was mechanistically driven by suppression of type I interferon as exogenous interferon-β reversed ACE2 downregulation by ICS. Mice deficient in the type I interferon-α/β receptor (Ifnar1−/−) also had reduced expression of ACE2. Collectively, these data suggest that use of ICS therapies in COPD reduces expression of the SARS-CoV-2 entry receptor ACE2 and this effect may thus contribute to altered susceptibility to COVID-19 in patients with COPD.

  • 原文来源：https://www.biorxiv.org/content/10.1101/2020.06.13.149039v1
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    • 编译者：zhangmin
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