When age, gender, and oral corticosteroid use were controlled for, no significant difference was observed in TMPRSS2 expression in sputum samples.  However, in both the bronchial brushings and the bronchial biopsies, there was a significant increase in TMPRSS2 expression in those with severe asthma who smoke versus those who had mild-to-moderate asthma and the healthy volunteer controls. 

Abbreviations used in the figure:

- SA: severe asthma
- ns: nonsmoker
- s: smoker
- MMA: mild-to-moderate asthma
- HV: healthy volunteer

Michigan State University

A  European U-BIOPRED  (Unbiased BIOmarkers Predictive of REspiratory Disease outcomes) cohort study examined the mRNA expression level of ACE2, TMPRSS2, and Furin in the sputum, bronchial brush and bronchial biopsies of volunteer subjects.  These three biomarkers are heavily involved in the pathogenesis of COVID-19, and it was hypothesized that these expression levels would correlate with asthma severity or other molecular phenotypes.  These findings may help to explain why those with asthma and other respiratory diseases are more vulnerable to SARS-CoV-2 infection and symptoms of COVID-19.

Wide European Cohort Study That Examines Expression Levels of COVID-19 Susceptible Biomarkers in Patients with Severe Asthma

Kermani, N., Song, W. J., Lunt, A., Badi, Y., Versi, A., Yike, G. U. O., ... & Sterk, P. (2020). Airway expression of SARS-CoV-2 receptor, ACE2, and proteases, TMPRSS2 and furin, in severe asthma. medRxiv.
https://www.medrxiv.org/content/10.1101/2020.06.29.20142091v1

Airway expression of SARS-CoV-2 receptor, ACE2, and proteases, TMPRSS2 and furin, in severe asthma

When age, gender, and oral corticosteroid use were controlled for, a significant increase in ACE2 expression was observed in sputum samples from those with severe asthma who didn't smoke versus those who had mild-to-moderate asthma and the healthy volunteer controls.  No significant difference was observed in the other two sample types.  

Abbreviations used in the figure:
- SA: severe asthma
- ns: nonsmoker
- s: smoker
- MMA: mild-to-moderate asthma
- HV: healthy volunteer

ACE2 Expression by Severity of Asthma

TMPRSS2 Expression by Severity of Asthma

When age, gender, and oral corticosteroid use were controlled for, a significant increase in furin expression was observed in sputum samples from those with severe asthma who didn't smoke versus those who had mild-to-moderate asthma and the healthy volunteer controls. A significant increase in furin expression was observed in those with severe asthma who smoke versus the healthy control volunteers.  Expression level in the bronchial biopsies were similar regardless of the severity of asthma.  

Abbreviations used in the figure:

- SA: severe asthma
- ns: nonsmoker
- s: smoker
- MMA: mild-to-moderate asthma
- HV: healthy volunteer

Furin Expression by Severity of Asthma

Transcriptomic-associated clusters (TACs) are groups of genes that determine the endotype, or subcategory, of asthma.  There are three TACs of asthma that differ based on their autoimmune response.  They have the following phenotypes:

- TAC1: eosinophilic inflammation; high levels of T2
- TAC2: neutrophilic inflammation; presence of imflammasome activation
- TAC3: paucigranulocytic inflammation

ACE2, TMPRSS2, and Furin expression levels were determined from sputum samples from those who were asthmatic as well as healthy volunteer controls.  These findings suggest that the mechanisms used by TAC1 and TAC2 may increase the expression of ACE2 and furin.  Additionally, this shows that genetic differences may contribute to the severity of COVID-19 in those with asthma.  

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