COVID-19 and nicotine as a mediator of ACE-2

Leung, Janice M.; Yang, Chen Xi; Sin, Don D.

doi:10.1183/13993003.01261-2020

Cited by 81 publications

(79 citation statements)

References 11 publications

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“…Two interesting publications in the European Respiratory Journal recently by Russo et al 1 and Leung et al 2 discuss the possible role of nicotine in this pandemic and the "furious pursuit for better therapeutics".…”

mentioning

confidence: 99%

Could the smoking gun in the fight against COVID-19 be the (rh)ACE-2?

Lutchman

2020

Eur Respir J

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confidence: 99%

Could the smoking gun in the fight against COVID-19 be the (rh)ACE-2?

Lutchman

2020

Eur Respir J

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“…Notably, ACE2 is clearly expressed in goblet cells, although it has been demonstrated that SARS-CoV and SARS-CoV-2 cannot infect goblet cells in both airway and intestinal epithelia (Lamers et al 2020 ). Moreover, the nAChR that was mostly co-expressed with ACE2 and TMPRSS2 was α7 nAChR (encoded by CHRNA7 ).…”

Section: Resultsmentioning

confidence: 99%

“…The gastrointestinal tract was therefore introduced as target organ for SARS-CoV-2 infection with up to 34% of COVID-19 patients reporting digestive symptoms like diarrhea, nausea, and abdominal discomfort (Yang and Tu 2020 ). The virus can propagate through ACE2 expressing enterocytes, and viral RNA can be found in rectal swabs, even after negative nasopharyngeal testing (Lamers et al 2020 ; Amirian 2020 ; Xiao et al 2020 ).…”

Section: Introductionmentioning

confidence: 99%

The role of nicotinic receptors in SARS-CoV-2 receptor ACE2 expression in intestinal epithelia

et al. 2020

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Background Recent evidence demonstrated that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) propagates in intestinal epithelial cells expressing Angiotensin-Converting Enzyme 2 (ACE2), implying that these cells represent an important entry site for the viral infection. Nicotinic receptors (nAChRs) have been put forward as potential regulators of inflammation and of ACE2 expression. As vagus nerve stimulation (VNS) activates nAChRs, we aimed to investigate whether VNS can be instrumental in affecting intestinal epithelial ACE2 expression. Methods By using publicly available datasets we qualified epithelial ACE2 expression in human intestine, and assessed gene co-expression of ACE2 and SARS-CoV-2 priming Transmembrane Serine Protease 2 (TMPRSS2) with nAChRs in intestinal epithelial cells. Next, we investigated mouse and human ACE2 expression in intestinal tissues after chronic VNS via implanted devices. Results We show co-expression of ACE2 and TMPRSS2 with nAChRs and α7 nAChR in particular in intestinal stem cells, goblet cells, and enterocytes. However, VNS did not affect ACE2 expression in murine or human intestinal tissue, albeit in colitis setting. Conclusions ACE2 and TMPRSS2 are specifically expressed in epithelial cells of human intestine, and both are co-expressed with nAChRs. However, no evidence for regulation of ACE2 expression through VNS could be found. Hence, a therapeutic value of VNS with respect to SARS-CoV-2 infection risk through ACE2 receptor modulation in intestinal epithelia could not be established.

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“…In addition, nicotine impairs the renin-angiotensin system (RAS) homeostasis [21], so nicotine-induced imbalance of RAS via nAChRs is a strong candidate to understand hypertension, dysregulated cardiac remodelling, vascular dysfunction and chronic lung diseases associated with severe forms of COVID-19. Interestingly, CHRNA7 transcripts were correlated with hACE2 levels [51] feeding the possible connections between hACE2 and nAChRs localizations in airways [52][53][54].…”

Section: Discussionmentioning

confidence: 99%

Nicotinic receptors atlas in the adult human lung

Diabasana

Perotin-Collard

Belgacemi

et al. 2020

Preprint

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ABSTRACTNicotinic acetylcholine receptors (nAChRs) are pentameric ligand-gated ion channels responsible for the rapid neural and neuromuscular signal transmission. Although it is well documented that 16 subunits are encoded by the human genome, their presence in airway epithelial cells (AEC) remains poorly understood, and contribution to pathology is mainly discussed in the context of cancer. We analysed nAChR subunit expression in the human lung of smokers and non-smokers using transcriptomic data for whole lung tissues, isolated large AEC, and isolated small AEC. We identified differential expressions of nAChRs in terms of detection and repartition in the three modalities. Smoking-associated alterations were also unveiled. Then, we identified a nAChR transcriptomic print at a single cell level. Finally, we reported the localizations of detectable nAChRs in bronchi and large bronchioles. Thus, we compiled the first complete atlas of pulmonary nAChRs to open new avenues to further unravel the involvement of these receptors in lung homeostasis and respiratory diseases.

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COVID-19 and nicotine as a mediator of ACE-2

Cited by 81 publications

References 11 publications

Could the smoking gun in the fight against COVID-19 be the (rh)ACE-2?

Could the smoking gun in the fight against COVID-19 be the (rh)ACE-2?

The role of nicotinic receptors in SARS-CoV-2 receptor ACE2 expression in intestinal epithelia

Nicotinic receptors atlas in the adult human lung

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