Sputum ACE2, TMPRSS2 and FURIN gene expression in severe neutrophilic asthma

Nazanin Zounemat Kermani, Woo Jung Song, Yusef Badi, Ali Versi, Yi-Ke GUO, Kai Sun, Pank Bhavsar, Peter Howarth, Sven Erik Dahlen, Peter J. Sterk, Ratko Djukanovic, Ian M. Adcock, Kian Fan Chung*, Uruj Hoda, Christos Rossios, Elisabeth Bel, Navin Rao, David Myles, Chris Compton, Marleen Van GeestGraham Roberts, Diane Lefaudeux, Bertrand De Meulder, Aruna T. Bansal, Richard Knowles, Damijn Erzen, Scott Wagers, Norbert Krug, Tim Higenbottam, John Matthews, Veit Erpenbeek, Leon Carayannopoulos, Amanda Roberts, David Supple, Pim deBoer, Massimo Caruso, Pascal Chanez, Ildikó Horváth, Nobert Krug, Jacek Musial, Thomas Sandström, U-BIOPRED Consortium

*Corresponding author for this work

    Research output: Contribution to journalJournal articlepeer-review

    29 Citations (Scopus)


    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.

    Original languageEnglish
    Article number10
    Number of pages11
    JournalRespiratory Research
    Issue number1
    Publication statusPublished - 7 Jan 2021

    Scopus Subject Areas

    • Pulmonary and Respiratory Medicine

    User-Defined Keywords

    • ACE2
    • FURIN
    • Neutrophil
    • Severe asthma
    • TMPRSS2


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