Alcohol potentiates RSV-mediated injury to ciliated airway epithelium

Wyatt, Todd A.; Bailey, Kristina L.; Simet, Samantha M.; Warren, Kristi J.; Sweeter, Jenea M.; DeVasure, Jane M.; Pavlik, Jaqueline A.; Sisson, Joseph H.

doi:10.1016/j.alcohol.2018.07.010

Cited by 16 publications

(12 citation statements)

References 46 publications

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“…These and many other genes related to these functions were significantly upregulated in lesions of group 6, in which viral shedding, clinical scores and lung pathology were lowest through the course of the disease due to the most effective combination and earliest start of the treatment. Mucociliary clearance-mediated innate immunity is an important component of antiviral protection in the lung and RSV both reduces the number of motile cilia and causes detachment of ciliated epithelial cells [ 51 , 52 ]. In our study, it is likely that an increase in expression of genes responsible for cilia and their motility in the treatment group in which BRSV caused minimal damage, played an important role in lung defense.…”

Section: Discussionmentioning

confidence: 99%

Analysis of lung transcriptome in calves infected with Bovine Respiratory Syncytial Virus and treated with antiviral and/or cyclooxygenase inhibitor

et al. 2021

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Bovine Respiratory Syncytial virus (BRSV) is one of the major infectious agents in the etiology of the bovine respiratory disease complex. BRSV causes a respiratory syndrome in calves, which is associated with severe bronchiolitis. In this study we describe the effect of treatment with antiviral fusion protein inhibitor (FPI) and ibuprofen, on gene expression in lung tissue of calves infected with BRSV. Calves infected with BRSV are an excellent model of human RSV in infants: we hypothesized that FPI in combination with ibuprofen would provide the best therapeutic intervention for both species. The following experimental treatment groups of BRSV infected calves were used: 1) ibuprofen day 3–10, 2) ibuprofen day 5–10, 3) placebo, 4) FPI day 5–10, 5) FPI and ibuprofen day 5–10, 6) FPI and ibuprofen day 3–10. All calves were infected with BRSV on day 0. Daily clinical evaluation with monitoring of virus shedding by qRT-PCR was conducted. On day10 lung tissue with lesions (LL) and non-lesional (LN) was collected at necropsy, total RNA extracted, and RNA sequencing performed. Differential gene expression analysis was conducted with Gene ontology (GO) and KEGG pathway enrichment analysis. The most significant differential gene expression in BRSV infected lung tissues was observed in the comparison of LL with LN; oxidative stress and cell damage was especially noticeable. Innate and adaptive immune functions were reduced in LL. As expected, combined treatment with FPI and Ibuprofen, when started early, made the most difference in gene expression patterns in comparison with placebo, especially in pathways related to the innate and adaptive immune response in both LL and LN. Ibuprofen, when used alone, negatively affected the antiviral response and caused higher virus loads as shown by increased viral shedding. In contrast, when used with FPI Ibuprofen enhanced the specific antiviral effect of FPI, due to its ability to reduce the damaging effect of prostanoids and oxidative stress.

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Section: Discussionmentioning

confidence: 99%

Analysis of lung transcriptome in calves infected with Bovine Respiratory Syncytial Virus and treated with antiviral and/or cyclooxygenase inhibitor

et al. 2021

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“…If the heavy drinker also smokes cigarettes, which occurs frequently ( DiFranza & Guerrera, 1990 ), the cilia may be actively slowed through the action of Protein Kinase C epsilon ( Wyatt et al, 2012 ), an enzyme upregulated in the airway ciliated cells of older persons ( Bailey, Kharbanda, Katafiasz, Sisson, & Wyatt, 2018 ). Indeed, both the duration and intensity of respiratory viral infection is increased in animal models of cigarette smoke and alcohol co-exposure ( Wyatt et al, 2019 ). It is not known how heavy alcohol intake affects mucus quantity or quality in the lung.…”

Section: Auds and The Lungmentioning

confidence: 99%

“…While less than 15% of consumed alcohol enters the lung, exhalation is nonetheless a significant process for alcohol excretion as evidenced by the common use of the Breathalyzer Test to reliably estimate blood alcohol levels ( Borkenstein & Smith, 1961 ). Heavy alcohol intake profoundly changes pulmonary innate and adaptive immunity, leading to higher rates of viral pneumonia ( de Roux et al, 2006 ), influenza A infection ( Greenbaum et al, 2014 ), respiratory syncytial virus (RSV) infection ( Jerrells et al, 2007 ; Wyatt et al, 2019 ), and bacterial pneumonia ( Cappa & Coleman, 1923 ; Fernández-Solá et al, 1995 ; Saitz, Ghali, & Moskowitz, 1997 ). In the 1918 influenza pandemic, heavy alcohol intake was recognized as a risk factor for poor outcomes ( Oxford, 2000 ).…”

Section: Introductionmentioning

confidence: 99%

Alcohol use disorder: A pre-existing condition for COVID-19?

Bailey

Samuelson

Wyatt

2021

Alcohol

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Alcohol misuse is long established as a contributor to the pathophysiology of the lung. The intersection of multi-organ responses to alcohol-mediated tissue injury likely contributes to the modulation of lung in response to injury. Indeed, the negative impact of alcohol on susceptibility to infection and on lung barrier function is now well documented. Thus, the alcohol lung represents a very likely comorbidity for the negative consequences of both COVID-19 susceptibility and severity. In this review, we present the known alcohol misuse ramifications on the lung in the context of the current coronavirus pandemic.

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“…During the pandemic, reports have highlighted the increase in alcohol consumption and the increased risk to trigger or exacerbate depressive and anxious episodes (4). Excessive consumption of alcohol can impair the immune response (5) present a deleterious effect in chronic viral infection (6,7) and increase the severity and recovery time for respiratory infections (8)(9)(10)(11).…”

Section: Introductionmentioning

confidence: 99%

Clinical Characteristics and Survival Analysis in Frequent Alcohol Consumers With COVID-19

et al. 2021

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Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection can generate a systemic disease named coronavirus disease–2019 (COVID-19). Currently, the COVID-19 pandemic has killed millions worldwide, presenting huge health and economic challenges worldwide. Several risk factors, such as age, co-infections, metabolic syndrome, and smoking have been associated with poor disease progression and outcomes. Alcohol drinking is a common social practice among adults, but frequent and/or excessive consumption can mitigate the anti-viral and anti-bacterial immune responses. Therefore, we investigated if patients with self-reported daily alcohol consumption (DAC) presented alteration in the immune response to SARS-CoV-2. We investigated 122 patients with COVID-19 (101 male and 46 females), in which 23 were patients with DAC (18 men and 5 women) and 99 were non-DAC patients (58 men and 41 women), without other infections, neoplasia, or immunodeficiencies. Although with no difference in age, patients with DAC presented an increase in severity-associated COVID-19 markers such as C-reactive protein (CRP), neutrophil count, and neutrophil-to-lymphocyte ratio. In addition, patients with DAC presented a reduction in the lymphocytes and monocytes counts. Importantly, the DAC group presented an increase in death rate in comparison with the non-DAC group. Our results demonstrated that, in our cohort, DAC enhanced COVID-19-associated inflammation, and increased the number of deaths due to COVID-19.

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Alcohol potentiates RSV-mediated injury to ciliated airway epithelium

Cited by 16 publications

References 46 publications

Analysis of lung transcriptome in calves infected with Bovine Respiratory Syncytial Virus and treated with antiviral and/or cyclooxygenase inhibitor

Analysis of lung transcriptome in calves infected with Bovine Respiratory Syncytial Virus and treated with antiviral and/or cyclooxygenase inhibitor

Alcohol use disorder: A pre-existing condition for COVID-19?

Clinical Characteristics and Survival Analysis in Frequent Alcohol Consumers With COVID-19

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