Introduction
Coronavirus disease 2019 (COVID-19) is posing an unprecedented impact on
global health. COVID-19 infection caused by the SARS-CoV-2 virus has
been reported to be more common or severe in those male subjects aged
above 70 years old or those with pre-existing conditions such as
obesity, hypertension and diabetes or those who are cigarette smokers
(1-5). A few studies have not reported a significant association between
asthma and critical outcomes in COVID-19 patients (1-5). However, a
large population-based study of ~11,000 COVID-related
deaths in the UK reported a higher risk of death in patients with severe
asthma who developed COVID-19 disease but not in those with non-severe
asthma (6), while another study of COVID-19 hospitalisations in the UK
showed that adults with asthma, particularly those with non-allergic
asthma, were at a higher risk of severe COVID-19 infection (7).
One of the potential determinants of the severity of SARS-CoV2 infection
is the degree of activation and multiplication of this new emergent
virus in human cells (8, 9). The spike protein of SARS-CoV-2 is used by
the virus to engage and bind its target cell receptor, the angiotensin
converting enzyme 2 (ACE2) (10). In addition, the spike protein needs to
be activated and degraded by host cell enzyme proteases, such as
transmembrane protease, serine 2
(TMPRSS2) and FURIN also known as PACE (Paired basic Amino acid Cleaving
Enzyme) (11, 12), which are essential for the proteolytic activation of
SARS-CoV-2 in human airway epithelial cells (13). Because this is the
mechanism by which SARS-CoV-2 infects and actively replicates in
respiratory tract cells, we tested the hypothesis that the expression of
these receptors and proteases needed by the virus may vary according to
asthma severity or to molecular phenotypes.
Our approach was to study the participants in the U-BIOPRED
(U nbiasedBIO markers P redictive of RE spiratoryD isease outcomes) study (14), which was a cohort study for
analysis of clinical and molecular features of severe asthma. Therefore,
these patients had undergone detailed clinical and physiologic
characterisation, with gene profiling studies of various lung and blood
samples. We examined the transcriptomic data obtained from 3 different
compartments of airway cells, namely, bronchial brushings, bronchial
biopsies and sputum-derived cells from patients with severe asthma
compared to those with mild-to-moderate asthma and to non-asthmatic
controls and analysed the expression of genes that encode for ACE2,
TMPRSS2 and FURIN. We also examined the relationship of the gene
expression with demographic and clinical parameters, and with asthma
molecular phenotypes or transcriptomic-associated clusters (TACs),
previously identified in the U-BIOPRED (15).