Airways Expression of SARS-CoV-2 Receptor, ACE2, and TMPRSS2 Is Lower in Children Than Adults and Increases with Smoking and COPD

Abstract

It has been reported that angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) are the main cell entry proteins for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and play a critical role in causing coronavirus disease 2019 . To investigate the expression level of these SARS-CoV-2 host cell entry genes in the lung airway, we used public gene expression datasets. We have found a differential expression of ACE2 and TMPRSS2 in nasal and bronchial airways relative to age and diseases status. Children were found to have significantly lower expression of COVID-19 receptors in the upper and lower airways (nasal and bronchial). Moreover, the lung airway expression of both ACE2 and TMPRSS2 was found to be significantly upregulated in smokers compared with non-smokers, and in patients with chronic obstructive pulmonary disease (COPD) compared with healthy subjects. No difference was observed in the blood expression levels of ACE2 and TMPRSS2 between children and adults, or in COPD or diabetic patients. However, a significant increase in blood expression levels of these genes was observed in patients with essential hypertension, whereas only ACE2 was upregulated in the blood of asthmatics. These results suggest that the observed difference in COVID-19 severity between children and adults could, in part, be attributed to the difference in ACE2 and TMPRSS2 airways tissue expression levels.

Are patients with chronic rhinosinusitis with nasal polyps at a decreased risk of COVID‐19 infection?

“…This may suggest that neutrophilic inflammation and the associated cytokines such as IFNγ and IL17 may upregulate COVID‐19 receptors levels and thus facilitate COVID‐19 infectivity. This data is also in line with our previous finding 5 indicating that patients with chronic obstructive pulmonary disease, characterized with neutrophilic inflammation, have significantly elevated ACE2 and TMPRSS2 lung tissue levels.…”

“…This was attributed to the difference in ACE2 expression between both tissues 4 . Recently, we have also shown that the upper airway expresses more SARS‐CoV‐2 entry genes, ACE2 and TMPRSS2, compared to the lower airway 5 . Moreover, Hou et al 6 .…”

A novel isoform ofACE2is expressed in human nasal and bronchial respiratory epithelia and is upregulated in response to RNA respiratory virus infection

“…Other strategies aim to use purified soluble recombinant ACE2, or ACE2+-small extracellular vesicles 59 to 'intercept' the virus before entry into host cells, avoiding infection. Our discovery also has implications for the numerous studies reporting on ACE2 expression levels and differences in levels of expression along airways, across age groups and disease groups 29,46,60,61 including COVID-19 disease severity 61,62 . This finding should be considered in in choice of Alignment files were assessed for saturation of known splice junctions using RSeqQC v3.0.1 71 .…”

A potent SARS-CoV-2 neutralizing human monoclonal antibody that reduces viral burden and disease severity in Syrian hamsters

“…The emergence of a novel coronavirus disease (COVID- 19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first described in December 2019 in Wuhan, China 1 .…”

“…Each protomer consists of an S1 domain, which mediates receptor binding, and an S2 domain that mediates membrane fusion and cell infection following conformational changes induced by host cell receptor binding [12][13][14] . The receptor for SARS-CoV, SARS-CoV-2 and HCoV-NL63 is angiotensin converting enzyme 2 (ACE2), which is expressed on mucosal epithelia of the upper respiratory tract, bronchioles, lungs and the GI tract [15][16][17][18][19] .…”