COVID-19–related Genes in Sputum Cells in Asthma. Relationship to Demographic Features and Corticosteroids

Peters, Michael C.; Sajuthi, Satria; DeFord, Peter; Christenson, Stephanie A.; Rios, Cydney; Montgomery, Michael T.; Woodruff, Prescott G.; Mauger, David T.; Erzurum, Serpil C.; Johansson, Mats W.; Denlinger, Loren C.; Jarjour, Nizar N.; Castro, Mario; Hastie, Annette T.; Moore, Wendy C.; Ortega, Victor E.; Bleecker, Eugene R.; Wenzel, Sally E.; Israel, Elliot; Levy, Bruce D.; Seibold, Max A.; Fahy, John V.

doi:10.1164/rccm.202003-0821oc

Cited by 414 publications

(453 citation statements)

References 24 publications

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“…There were no significant differences between these groups in terms of age, disease severity, smoking status or other comorbidities known to affect ACE2 expression and/or associated with increased risk of COVID-19 ( Table 1). Sputum cell ACE2 mRNA expression was detectable in 22/36 COPD subjects (61.1%) and, consistent with prior observations in asthma (17), significantly reduced in ICS users compared to nonusers (Fig 1a). Sputum cell expression of the serine protease TMPRSS2 that is used by SARS-CoV-2 for mucosal entry (13) was detectable in all subjects with no significant difference observed between ICS users and non-users (Fig 1b).…”

Section: Ace2 Mrna Expression Is Reduced In Copd Patients Taking Inhasupporting

confidence: 91%

“…ACE2 is expressed primarily in the nasal goblet cells and type II pneumocytes within the respiratory tract (30) and is upregulated in subject groups known to be associated with increased disease severity including elderly individuals (31) and patients with diabetes (17), indicating that it may play a clinically important role in governing susceptibility to virus acquisition and/or development of severe disease in at-risk groups. ACE2 expression has similarly been shown to be increased in COPD: using combined transcriptomic and immunohistochemical analyses, Leung et al recently demonstrated that epithelial ACE2 expression is increased in bronchial brushings/tissue samples from COPD subjects versus healthy controls (32), effects also previously shown in cigarette smoke exposure animal models (33).…”

Section: Discussionmentioning

confidence: 99%

“…Currently, a direct causal link between ACE2 and increased susceptibility to acquisition of SARS-CoV-2 or subsequent severity has not been proven and we cannot conclude unequivocally that downregulation of ACE2 by ICS is an effect that would confer protection clinically. In asthma, a disease where ICS are more commonly prescribed than in COPD, ACE2 expression is reduced compared to healthy subjects (15) and also further attenuated in ICS users (17). In contrast to COPD, asthma has not been shown to be associated with increased COVID-19 mortality (5) and the more widespread use of ICS with associated suppression of ACE2 could theoretically be one factor driving this.…”

Section: Discussionmentioning

confidence: 99%

“…Increased epithelial ACE2 expression has been recently reported in smokers and subjects with COPD (14) and is postulated to be a factor predisposing these individuals to adverse outcome from COVID-19. Conversely, ACE2 is downregulated in asthma (15), an effect that may be due to suppressive effects of type 2 cytokines (16) or related to ICS use (17).…”

Section: Introductionmentioning

confidence: 99%

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Inhaled corticosteroids downregulate the SARS-CoV-2 receptor ACE2 in COPD through suppression of type I interferon

Finney

Glanville²,

Farne

et al. 2020

Preprint

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Coronavirus disease 2019 caused by SARS-CoV-2 is a new rapidly spreading infectious disease. Early reports of hospitalised COVID-19 cases have shown relatively low frequency of chronic lung diseases such as chronic obstructive pulmonary disease (COPD) but increased risk of adverse outcome. The mechanisms of altered susceptibility to viral acquisition and/or severe disease in at-risk groups are poorly understood. Inhaled corticosteroids (ICS) are widely used in the treatment of COPD but the extent to which these therapies protect or expose patients with a COPD to risk of increased COVID-19 severity is unknown. Here, using a combination of human and animal in vitro and in vivo disease models, we show that ICS administration attenuates pulmonary expression of the SARS-CoV-2 viral entry receptor angiotensin-converting enzyme (ACE)-2. This effect was mechanistically driven by suppression of type I interferon as exogenous interferon-β reversed ACE2 downregulation by ICS.Mice deficient in the type I interferon-α/β receptor (Ifnar1 −/− ) also had reduced expression of ACE2.Collectively, these data suggest that use of ICS therapies in COPD reduces expression of the SARS-CoV-2 entry receptor ACE2 and this effect may thus contribute to altered susceptibility to COVID-19 in patients with COPD.

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Section: Ace2 Mrna Expression Is Reduced In Copd Patients Taking Inhasupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Inhaled corticosteroids downregulate the SARS-CoV-2 receptor ACE2 in COPD through suppression of type I interferon

Finney

Glanville²,

Farne

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…The use of Betamehasone and Dexamehasone effect on hinge site blockage not been explored, the two corticosteroids have the same molecular weight and high structural similarity (the only difference is the orientation of the methyl group on carbon 16) so which could have similar effects. Use of inhaled corticosteroids had been associated with lower expression of ACE2 and TMPRSS2, but treatment with Triamcinolone Acetonide did not decrease expression of either gene [19]. On the other hand, the use of Atazanavir (protease inhibitor) has been reported in computer studies with inhibitory potency activity with Kd of 94.94 nM against the SARS-CoV-2 3C-like protease inhibitor [2].…”

Section: Discussionmentioning

confidence: 99%

Repositioning of ligands that target spike glycoprotein as potential drugs against SARS-CoV-2

Ramírez-Salinas¹,

Martínez‐Archundia²,

Correa-Basurto³

et al. 2020

Preprint

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The worldwide health emergency of the SARS-CoV-2 pandemic and the absence of a specific treatment for this new coronavirus have led to the use of computational strategies (drug repositioning) to search for treatments. The aim of this work is to identify FDA-approved drugs with the potential for binding to the spike structural glycoprotein at the hinge site, receptor binding motif (RBM), and fusion peptide (FP) using molecular docking simulations. It was identified drugs that binding to amino acids crucial for down to up conformational change, receptor recognition, and fusion of the viral membrane with the cell membrane. Results show some drugs that bind to hinge site amino acids (Varenicline, or even steroids as Betamethasone) while other drugs bind to crucial amino acids for RBM (Naldemedine, Atovaquone, Cefotetan) or FP (Edarbi, Maraviroc, Difluprednate); and highlights the Saquinavir that binds both the RBM and the FP. Therefore, these drugs could inhibit spike glycoprotein and prevent viral entry (possible anti-COVID-19 drugs). Several drugs are in clinical studies; focused on another pharmacological target (candesartan, Atovaquone, Losartan, Maviroc and Ritonavir) in this work we propose an additional target, the spike glycoprotein. These results can impact in the proposal of treatments that can inhibit the first steps virus replication cycle.

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How Should Educators and Publishers Eliminate Racial Essentialism?

Tsai¹

2022

AMA Journal of Ethics

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Racial essentialism-the belief that socially constructed racial categories reflect "inherent" biological differences-exacerbates learners' racial prejudice and diminishes their empathy. Essentialism hinders health professions education programs' capacity to generate a health care work force that motivates ethics and equity in health care and research. This article suggests how health professions educators and institutions should reform pedagogy on race, when clinically relevant, to emphasize racism as the root cause of health inequity. Publishers of research also have key roles in reform and should enforce appropriate and just references to race in journals and health professions education content.

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COVID-19–related Genes in Sputum Cells in Asthma. Relationship to Demographic Features and Corticosteroids

Cited by 414 publications

References 24 publications

Inhaled corticosteroids downregulate the SARS-CoV-2 receptor ACE2 in COPD through suppression of type I interferon

Inhaled corticosteroids downregulate the SARS-CoV-2 receptor ACE2 in COPD through suppression of type I interferon

Repositioning of ligands that target spike glycoprotein as potential drugs against SARS-CoV-2

How Should Educators and Publishers Eliminate Racial Essentialism?

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