Effect of vaping on COVID-19 infection

项目总结 在新冠肺炎疫情中，150多万美国人患病，100,000多人死亡。到目前为止, 医疗服务不足的人群死亡或发展成危重疾病的可能性是他们的 在人口中的比例。现吸烟者和曾经吸烟者也更有可能患上临界新冠肺炎 和/或死亡。其基础可能是社会、行为和/或生理上的。最近的研究结果表明， 吸烟和尼古丁可能会改变病毒进入呼吸道上皮的‘对接部位’(ACE2)。这 这项研究将探索蒸发和尼古丁对对新冠肺炎敏感的仓鼠的影响，看看这是否 由于SARS-CoV-2病毒改变了他们的肺ACE2表达和/或加重了他们的疾病。蒸发是一种 令人上瘾的、有毒的和血管活性化合物尼古丁的输送装置。电子烟的使用，或双重使用 传统香烟和电子烟，尚未在SARS-CoV-2感染的背景下进行审查。具体地说， 汽化和尼古丁对新冠肺炎肺疾病严重程度、病毒载量和血管紧张素转换酶2/血管紧张素转换酶表达的影响 将对消息、蛋白质和活动水平进行调查。因此，该模型将用于澄清 蒸发诱导的肺损伤对ACE2表达和随后的SARS2感染的重要性 发病机制。为了解决这些问题，我们假设亚急性和/或急性尼古丁蒸发 可以改变ACE2/ACE的活性，并可能改变仓鼠的肺组织病理学。此外，我们 推测急性/亚急性蒸发可增加SARS-CoV-2感染和/或肺部疾病 仓鼠的严重度。如果属实，汽化和/或手术中ACE2/ACE比率的药理学修改 非蒸发仓鼠可减轻SARS-CoV-2感染严重程度。我们将会达到两个目标： 1)明确蒸发尼古丁对叙利亚仓鼠ACE2/ACE和肺组织病理学的影响，以及 2)明确汽化对SARS-CoV-2病毒载量、清除和新冠肺炎肺部疾病的影响 在目标1中开发的模型(S) 方法：我们将使用一款新获得的电子烟“蒸发机器人”，它是完全计算机化的 使用FlexiWare软件(InExpose，SCIREQ，蒙特利尔)进行编程，仅通过鼻子递送给啮齿动物，以及 新近报道了SARS-CoV-2介导的肺损伤的仓鼠模型。蒸发曝光量将是 在科罗拉多大学安舒茨医学院(丹佛)进行，在短暂的运输之后， 新冠肺炎模型将在科罗拉多州立大学(科罗拉多州立大学)BSL3设施(Ft.科林斯，科林斯)我们到了 将监测仓鼠长达7天，研究呼吸道/肺组织病理学和ACE2/ACE表达 验尸后。该项目涉及两个具有长期研究兴趣的实验室：急性肺损伤 毒理学、病毒学和新出现的病原体。我们将更好地理解机制(S) 对于吸烟者新冠肺炎的恶化，以及可能获得更有效治疗的新途径。

PROJECT SUMMARY In the COVID-19 pandemic, >1.5 million Americans have become ill, and over 100,000 have died. So far, medically underserved populations are more than twice as likely to die or develop critical illness relative to their proportion in the population. Current and former smokers are also more likely to develop critical COVID-19 and/or die. The basis for this could be social, behavioral and/or physiological. Recent findings show that smoking and nicotine may change the ‘docking site’ (ACE2) where the virus enters the airway epithelium. This study will explore the effect of vaping and nicotine in hamsters that are susceptible to COVID-19 to see if this changes their lung ACE2 expression and/or worsens their disease due to the SARS-CoV-2 virus. Vaping is a delivery device for the addicting, toxic and vasoactive compound nicotine. E-cigarette use, or dual use of traditional and e-cigarettes, has not been examined in the context of SARS-CoV-2 infection. Specifically, the effects of vaping and nicotine on COVID-19 lung disease severity, viral load, and ACE2/ACE expression at the message, protein and activity levels will be investigated. Thus, this model will be used to clarify the importance of vaping-induced lung injury on ACE2 expression and subsequent SARS2 infection and pathogenesis. To address these questions, we hypothesized that subacute and/or acute nicotine vaping could alter the ACE2/ACE activities and, potentially, lung histopathology in the hamster. Further, we postulated that acute/subacute vaping could increase SARS-CoV-2 infection and/or lung disease severity in the hamster. If true, pharmacologic modification of ACE2/ACE ratio in the vaping and/or nonvaping hamster could diminish SARS-CoV-2 infection severity. Two aims will be undertaken: 1) Define the effects of vaping nicotine on ACE2/ACE and lung histopathology in Syrian hamster, and 2)Define the effect of vaping on SARS-CoV-2 viral load, clearance, and COVID-19 lung disease in model(s) developed in Aim 1 APPROACH: We will use a newly acquired e-cigarette ‘vaping robot’ that is fully computerized and programmable using flexiWare software (inExpose, SCIREQ, Montreal) for nose-only delivery to rodents, and a recently described hamster model for SARS-CoV-2-mediated lung injury. The vaping exposures will be conducted at University of Colorado Anschutz Medical Campus (Denver), and, following brief transport, the COVID-19 model will be done at Colorado State University’s (CSU) BSL3 facility (Ft. Collins, CO). There we will monitor hamsters for up to 7 days, with studies of airway/lung histopathology and ACE2/ACE expression after necropsy. The project involves two laboratories with long-standing research interests: acute lung injury and toxicology, and virology and emerging pathogens, respectively. We will better understand mechanism(s) for worsening COVID-19 in smokers, and potentially new pathways to their more effective treatment.