Reduced ACE2 and TMPRSS2 immunopositive bronchial cells in asthmatics after inhaled allergen challenge

Abstract

Rationale: The incidence of SARS-CoV-2 infection and the impact of corticosteroid treatment in patients with symptomatic airway disease has been a concern. We examined airway expression of SARS-CoV-2 receptors following allergen challenge and steroid intervention in asthmatic patients.

Methods: From steroid-naïve mild allergic asthmatic (AA n=23) we collected endobronchial biopsies pre and 24hr post allergen inhalation challenge (AIC). In a subset of AA with allergic rhinitis (AR n=8) we collected inferior nasal turbinate biopsies pre and 24hr post-nasal allergen challenges (NAC) after placebo treatment or after 21 days of 22 mg BID triamcinolone nasal spray. FEV1 and PNIF expressed as % fall from baseline quantified the early (ER, 0-2h) and late (LR, 3-7h) airway responses post challenge. Epithelium and laminae propria were immunostained for ACE2 and TMPRSS2 and expressed as # cells/mm2.

Results: AIC reduced FEV1 (31% ER, 19% LR) and the number of bronchial cells immunopositive for ACE2, TMPRSS2 and double positive for ACE2/TMPRSS2 (P=0.0002, P=0.04, P=0.02, respectively). The PNIF reduction by NAC (69% ER, 49% LR) was attenuated by triamcinolone (31% ER, 18% LR), but without changes in ACE2 or TMPRSS2 in nasal tissue after NAC or steroid treatment (all P>0.05). In the nasal tissue, significantly fewer cells expressed ACE2 compared to bronchi (P=0.007).

Conclusion: ACE2 and TMPRSS2 expression in bronchial tissue is reduced in the T2 microenvironment post allergen challenge, however it is unknown if this protects lower airways from SARS-CoV-2 infection. Low expression of ACE2 and TMPRSS2 in nasal tissue made it difficult to determine the effects of NAC or steroid.