Nicotine Changes Airway Epithelial Phenotype and May Increase the SARS-COV2 Infection Severity

Lupacchini, Leonardo; Maggi, Fabrizio; Tomino, Carlo; Dominicis, Chiara De; Mollinari, Cristiana; Bonassi, Stefano; Merlo, Daniela; Russo, Patrizia

doi:10.20944/preprints202012.0467.v1

2020

DOI: 10.20944/preprints202012.0467.v1

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Nicotine Changes Airway Epithelial Phenotype and May Increase the SARS-COV2 Infection Severity

Leonardo Lupacchini¹,

Fabrizio Maggi²,

Carlo Tomino³

et al.

Abstract: (1) Background: Nicotine is implicated in the SARS-COV-2 infection through activation of the α7-nAChR and over-expression of ACE2. Our objective is to clarify the role of nicotine in SARS-CoV-2 infection exploring its molecular and cellular activity. (2) Methods: HBEpC or si-mRNA-α7-HBEpC were treated for 1, 48 h or continuously with 10-7 M Nicotine, a concentration mimicking human exposure to a cigarette. Cell viability and proliferation were evaluated by trypan blue dye exclusion and cell… Show more

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Cited by 7 publications

References 80 publications

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Lower Gene Expression of Angiotensin Converting Enzyme 2 Receptor in Lung Tissues of Smokers with COVID-19 Pneumonia

et al. 2021

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Angiotensin-converting enzyme 2 (ACE-2) is the main cell entry receptor for severe acute respiratory syndrome-Coronavirus-2 (SARS-CoV-2), thus playing a critical role in causing Coronavirus disease 2019 (COVID-19). The role of smoking habit in the susceptibility to infection is still controversial. In this study we correlated lung ACE-2 gene expression with several clinical/pathological data to explore susceptibility to infection. This is a retrospective observational study on 29 consecutive COVID-19 autopsies. SARS-CoV-2 genome and ACE-2 mRNA expression were evaluated by real-time polymerase chain reaction in lung tissue samples and correlated with several data with focus on smoking habit. Smoking was less frequent in high than low ACE-2 expressors (p = 0.014). A Bayesian regression also including age, gender, hypertension, and virus quantity confirmed that smoking was the most probable risk factor associated with low ACE-2 expression in the model. A direct relation was found between viral quantity and ACE-2 expression (p = 0.028). Finally, high ACE-2 expressors more frequently showed a prevalent pattern of vascular injury than low expressors (p = 0.049). In conclusion, ACE-2 levels were decreased in the lung tissue of smokers with severe COVID-19 pneumonia. These results point out complex biological interactions between SARS-CoV-2 and ACE-2 particularly concerning the aspect of smoking habit and need larger prospective case series and translational studies.

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Lower Gene Expression of Angiotensin Converting Enzyme 2 Receptor in Lung Tissues of Smokers with COVID-19 Pneumonia

et al. 2021

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Tryptophan Metabolites and Aryl Hydrocarbon Receptor in Severe Acute Respiratory Syndrome, Coronavirus-2 (SARS-CoV-2) Pathophysiology

Anderson¹,

Carbone

Mazzoccoli

2021

IJMS

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The metabolism of tryptophan is intimately associated with the differential regulation of diverse physiological processes, including in the regulation of responses to severe acute respiratory syndrome, coronavirus-2 (SARS-CoV-2) infection that underpins the COVID-19 pandemic. Two important products of tryptophan metabolism, viz kynurenine and interleukin (IL)4-inducible1 (IL41)-driven indole 3 pyruvate (I3P), activate the aryl hydrocarbon receptor (AhR), thereby altering the nature of immune responses to SARS-CoV-2 infection. AhR activation dysregulates the initial pro-inflammatory cytokines production driven by neutrophils, macrophages, and mast cells, whilst AhR activation suppresses the endogenous antiviral responses of natural killer cells and CD8+ T cells. Such immune responses become further dysregulated by the increased and prolonged pro-inflammatory cytokine suppression of pineal melatonin production coupled to increased gut dysbiosis and gut permeability. The suppression of pineal melatonin and gut microbiome-derived butyrate, coupled to an increase in circulating lipopolysaccharide (LPS) further dysregulates the immune response. The AhR mediates its effects via alterations in the regulation of mitochondrial function in immune cells. The increased risk of severe/fatal SARS-CoV-2 infection by high risk conditions, such as elderly age, obesity, and diabetes are mediated by these conditions having expression levels of melatonin, AhR, butyrate, and LPS that are closer to those driven by SARS-CoV-2 infection. This has a number of future research and treatment implications, including the utilization of melatonin and nutraceuticals that inhibit the AhR, including the polyphenols, epigallocatechin gallate (EGCG), and resveratrol.

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COVID-19 in Joint Ageing and Osteoarthritis: Current Status and Perspectives

Lauwers

Yuan

et al. 2022

IJMS

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COVID-19 is a trending topic worldwide due to its immense impact on society. Recent trends have shifted from acute effects towards the long-term morbidity of COVID-19. In this review, we hypothesize that SARS-CoV-2 contributes to age-related perturbations in endothelial and adipose tissue, which are known to characterize the early aging process. This would explain the long-lasting symptoms of SARS-CoV-2 as the result of an accelerated aging process. Connective tissues such as adipose tissue and musculoskeletal tissue are the primary sites of aging. Therefore, current literature was analyzed focusing on the musculoskeletal symptoms in COVID-19 patients. Hypovitaminosis D, increased fragility, and calcium deficiency point towards bone aging, while joint and muscle pain are typical for joint and muscle aging, respectively. These characteristics could be classified as early osteoarthritis-like phenotype. Exploration of the impact of SARS-CoV-2 and osteoarthritis on endothelial and adipose tissue, as well as neuronal function, showed similar perturbations. At a molecular level, this could be attributed to the angiotensin-converting enzyme 2 expression, renin-angiotensin system dysfunction, and inflammation. Finally, the influence of the nicotinic cholinergic system is being evaluated as a new treatment strategy. This is combined with the current knowledge of musculoskeletal aging to pave the road towards the treatment of long-term COVID-19.

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Nicotine Changes Airway Epithelial Phenotype and May Increase the SARS-COV2 Infection Severity

Cited by 7 publications

References 80 publications

Lower Gene Expression of Angiotensin Converting Enzyme 2 Receptor in Lung Tissues of Smokers with COVID-19 Pneumonia

Lower Gene Expression of Angiotensin Converting Enzyme 2 Receptor in Lung Tissues of Smokers with COVID-19 Pneumonia

Tryptophan Metabolites and Aryl Hydrocarbon Receptor in Severe Acute Respiratory Syndrome, Coronavirus-2 (SARS-CoV-2) Pathophysiology

COVID-19 in Joint Ageing and Osteoarthritis: Current Status and Perspectives

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