Expression of ACE2
In sputum, ACE2 levels were significantly higher in SA than in MMA (p =0.001) but was not different from HV (p =0.091) (Fig 1A ). Among asthmatics, ACE2 levels were significantly associated with blood eosinophils (%), blood neutrophils (%), post-bronchodilator (post-BD) FEV1 (% predicted), OCS use, and severe asthma in univariate linear regression (Table 1 ). In multivariate regression analyses, ACE2 expression levels were positively associated with male gender (correlation coefficient: 0.192; 95% confidence interval [95% CI]: 0.004 to 0.381; p =0.045) and OCS use (0.232; 95% CI: 0.025 to 0.440; p =0.029) (Fig 2A ). The effects of severe asthma or post-BD FEV1 (% predicted) on ACE2 levels became non-significant when adjusted for OCS use (data not shown). Positive association between sputum ACE levels and OCS use is presented in a box and whisker plot (Supplementary Fig S1 ).
In bronchial brushing and biopsy, ACE2 levels were not significantly associated with the presence of asthma, or asthma severity (Fig 1D and G ). In bronchial brushing, univariate regression analysis showed an inverse relationship between ACE2 levels and OCS use (Table 1 ), but the relationship was not significant on multivariate analysis (-0.380; 95% CI: -0.775 to 0.015; p =0.059; Fig 2B ). In bronchial biopsy, ever-smoking and ever-history of nasal polyps were significantly associated with ACE levels on univariate regression (Table 1 ), but both became non-significant on multivariate analysis (Fig 2C ).