Sputum ACE2, TMPRSS2 and FURIN gene expression in severe neutrophilic asthma
Authors: Veit Erpenbeek
Scott Wagers
Navin Rao
Thomas Sandström
Kian Fan Chung
Uruj Hoda
Peter J Sterk
Pim deBoer
Marleen Van Geest
Ildikó Horváth
Damijn Erzen
Richard Knowles
Nobert Krug
Chris Compton
Jacek Musial
Graham Roberts
Pascal Chanez
Nazanin Zounemat Kermani
Aruna T Bansal
Kai Sun
Massimo Caruso
John Matthews
Peter Howarth
Woo-Jung Song
Christos Rossios
Tim Higenbottam
Amanda Roberts
Sven-Erik Dahlen
Ali Versi
Ratko Djukanovic
Bertrand De Meulder
David Myles
Yike Guo
Ian M Adcock
Yusef Badi
Elisabeth Bel
Norbert Krug
Pank Bhavsar
David Supple
U-BIOPRED Consortium
Leon Carayannopoulos
Diane Lefaudeux
Journal: Respiratory Research (2021)
Discipline: CLINICAL MEDICINE
Keywords: ACE2; FURIN; Neutrophil; Severe asthma; TMPRSS2.
Affiliations: Data Science Institute, Imperial College London, London, UK., National Heart and Lung Institute, Imperial College London, Dovehouse St, London, SW3 6LY, UK., Department of Allergy and Clinical Immunology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea., Faculty of Medicine, Southampton University, Southampton, UK., NIHR Southampton Respiratory Biomedical Research Unit, University Hospital Southampton, Southampton, UK., Centre for Allergy Research, Karolinska Institute, Stockholm, Sweden., Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, Netherlands., Data Science Institute, Imperial College London, London, UK. ., National Heart and Lung Institute, Imperial College London, Dovehouse St, London, SW3 6LY, UK. .

Abstract:  Background: Patients with severe asthma may have a greater risk of dying from COVID-19 disease. Angiotensin converting enzyme-2 (ACE2) and the enzyme proteases, transmembrane protease serine 2 (TMPRSS2) and FURIN, are needed for viral attachment and invasion into host cells. Methods: We examined microarray mRNA expression of ACE2, TMPRSS2 and FURIN in sputum, bronchial brushing and bronchial biopsies of the European U-BIOPRED cohort. Clinical parameters and molecular phenotypes, including asthma severity, sputum inflammatory cells, lung functions, oral corticosteroid (OCS) use, and transcriptomic-associated clusters, were examined in relation to gene expression levels. Results: ACE2 levels were significantly increased in sputum of severe asthma compared to mild-moderate asthma. In multivariate analyses, sputum ACE2 levels were positively associated with OCS use and male gender. Sputum FURIN levels were significantly related to neutrophils (%) and the presence of severe asthma. In bronchial brushing samples, TMPRSS2 levels were positively associated with male gender and body mass index, whereas FURIN levels with male gender and blood neutrophils. In bronchial biopsies, TMPRSS2 levels were positively related to blood neutrophils. The neutrophilic molecular phenotype characterised by high inflammasome activation expressed significantly higher FURIN levels in sputum than the eosinophilic Type 2-high or the pauci-granulocytic oxidative phosphorylation phenotypes. Conclusion: Levels of ACE2 and FURIN may differ by clinical or molecular phenotypes of asthma. Sputum FURIN expression levels were strongly associated with neutrophilic inflammation and with inflammasome activation. This might indicate the potential for a greater morbidity and mortality outcome from SARS-CoV-2 infection in neutrophilic severe asthma. 

Retracted: No

PubPeer comments:
 2021 correction. https: respiratory-research.biomedcentral.com articles 10.1186 s12931-021-01642-x Following publication of the original article [1], we were notified that Fig 2b and 2c were duplicated. Figure 2c should be the data from bronchial biopsy. Also, in Additional Table S1, the values for Female Asthma and Control under Bronchial Brushing were swapped and the last table column should read u201cBronchial biopsyu201d instead of u201cBronchial Brushingu201d. ,