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.