Imperial College London
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DrAranSinganayagam

Faculty of Medicine, Department of Infectious Disease

MRC Clinician Scientist Fellow.
 
 
 
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Contact

 

a.singanayagam

 
 
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Location

 

Flowers buildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@unpublished{Finney:2020:10.1101/2020.06.13.149039,
author = {Finney, LJ and Glanville, N and Farne, H and Aniscenko, J and Fenwick, P and Kemp, SV and Trujillo-Torralbo, M-B and Calderazzo, MA and Wedzicha, JA and Mallia, P and Bartlett, NW and Johnston, SL and Singanayagam, A},
doi = {10.1101/2020.06.13.149039},
title = {Inhaled corticosteroids downregulate the SARS-CoV-2 receptor ACE2 in COPD through suppression of type I interferon},
url = {http://dx.doi.org/10.1101/2020.06.13.149039},
year = {2020}
}
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RIS format (EndNote, RefMan)

TY  - UNPB
AB  - <jats:title>Abstract</jats:title><jats:p>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<jats:italic>in vitro</jats:italic>and<jats:italic>in vivo</jats:italic>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 (<jats:italic>Ifnar1</jats:italic><jats:sup>−/−</jats:sup>) 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.</jats:p>
AU  - Finney,LJ
AU  - Glanville,N
AU  - Farne,H
AU  - Aniscenko,J
AU  - Fenwick,P
AU  - Kemp,SV
AU  - Trujillo-Torralbo,M-B
AU  - Calderazzo,MA
AU  - Wedzicha,JA
AU  - Mallia,P
AU  - Bartlett,NW
AU  - Johnston,SL
AU  - Singanayagam,A
DO  - 10.1101/2020.06.13.149039
PY  - 2020///
TI  - Inhaled corticosteroids downregulate the SARS-CoV-2 receptor ACE2 in COPD through suppression of type I interferon
UR  - http://dx.doi.org/10.1101/2020.06.13.149039
ER  -
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