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.