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).