Abstract
We previously reported higher ACE2 levels in smokers and patients with COPD. The current study investigates if patients with interstitial lung diseases (ILDs) such as IPF and LAM have elevated ACE2, TMPRSS2, and Furin levels, increasing their risk for SARS-CoV-2 infection and development of COVID-19. Surgically resected lung tissue from IPF, LAM patients, and healthy controls (HC) was immunostained for ACE2, TMPRSS2, and Furin. Percentage ACE2, TMPRSS2, and Furin expression was measured in small airway epithelium (SAE) and alveolar areas using computer-assisted Image-Pro Plus 7.0 software. IPF and LAM tissue was also immunostained for myofibroblast marker α-smooth muscle actin (α-SMA) and growth factor transforming growth factor beta1 (TGF-β1). Compared to HC, ACE2, TMPRSS2 and Furin expression were significantly upregulated in the SAE of IPF (p < 0.01) and LAM (p < 0.001) patients, and in the alveolar areas of IPF (p < 0.001) and LAM (p < 0.01). There was a significant positive correlation between smoking history and ACE2 expression in the IPF cohort for SAE (r = 0.812, p < 0.05) and alveolar areas (r = 0.941, p < 0.01). This, to our knowledge, is the first study to compare ACE2, TMPRSS2, and Furin expression in patients with IPF and LAM compared to HC. Descriptive images show that α-SMA and TGF-β1 increase in the IPF and LAM tissue. Our data suggests that patients with ILDs are at a higher risk of developing severe COVID-19 infection and post-COVID-19 interstitial pulmonary fibrosis. Growth factors secreted by the myofibroblasts, and surrounding tissue could further affect COVID-19 adhesion proteins/cofactors and post-COVID-19 interstitial pulmonary fibrosis. Smoking seems to be the major driving factor in patients with IPF.
Highlights
The coronavirus disease 2019 (COVID-19) outbreak has caused more than 240 million infections so far with approximately 4.9 million deaths worldwide until October 2021 [1].Chronic lung disease has been recognized as a risk factor for COVID-19 [2,3]
We further observed that angiotensin-converting enzyme 2 (ACE2), TMPRSS2, and Furin expression was increased majorly in alveolar type II pneumocytes in IPF and LAM, especially in IPF
We identified here that ACE2, TMPRSS2, and Furin are highly expressed on small airway epithelium and alveolar region
Summary
The coronavirus disease 2019 (COVID-19) outbreak has caused more than 240 million infections so far with approximately 4.9 million deaths worldwide until October 2021 [1].Chronic lung disease has been recognized as a risk factor for COVID-19 [2,3]. A recent study has indicated that smokers have almost two-times higher odds of progression of COVID-19 severity than non-smokers, which confirms that smoking is a risk factor for COVID-19 progression [4]. Leung et al [6] showed increased ACE2 gene expression in small airway epithelial cells of smokers and COPD patients, and the smoking status was significantly associated with the ACE2 gene expression levels in smokers, which was higher in smokers than non-smokers. Our study further indicated ACE2 protein expression was significantly increased in small airway epithelium, alveolar type II pneumocytes, and alveolar macrophages in current smokers with COPD compared to normal lung function smokers and normal controls [5]. We reported that increased ACE2 expression was associated with increased endocytic vacuoles in smokers and COPD patients [7] These results provided further evidence that smokers and COPD patients are highly susceptible to SARS-CoV-2 infection
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