Effect of vaping on COVID-19 infection

项目摘要 在COVID-19大流行中，超过150万美国人患病，超过10万人死亡。到目前为止， 医疗服务不足的人群死亡或患重症的可能性是他们的两倍多。 在人口中的比例。目前和以前的吸烟者也更有可能发展为严重的COVID-19 和/或死亡其基础可能是社会的、行为的和/或生理的。最近的研究结果表明， 吸烟和尼古丁可能改变病毒进入气道上皮的“对接点”（ACE 2）。这 这项研究将探讨电子烟和尼古丁对易感染COVID-19的仓鼠的影响，看看这是否会影响到它们的健康。 改变他们的肺ACE 2表达和/或使他们的疾病由于SARS-CoV-2病毒而减轻。Vaping是一个 一种成瘾性、毒性和血管活性化合物尼古丁的输送装置。电子烟使用，或双重使用 传统香烟和电子香烟尚未在SARS-CoV-2感染的背景下进行研究。具体而言是 电子烟和尼古丁对COVID-19肺部疾病严重程度、病毒载量和ACE 2/ACE表达的影响 将研究信息、蛋白质和活性水平。因此，该模型将用于澄清 电子烟诱导的肺损伤对ACE 2表达和随后的SARS 2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vaping 可能改变仓鼠的ACE 2/ACE活性，并可能改变肺组织病理学。我们还 假设急性/亚急性vaping可以增加SARS-CoV-2感染和/或肺部疾病， 仓鼠的严重性。如果是真的，药物改变vaping和/或 不吸电子烟的仓鼠可以减轻SARS-CoV-2感染的严重程度。将实现两个目标： 1)确定雾化尼古丁对叙利亚仓鼠ACE 2/ACE和肺组织病理学的影响， 2)确定vaping对SARS-CoV-2病毒载量，清除和COVID-19肺部疾病的影响， 目标1中开发的模型 方法：我们将使用一种新获得的电子烟“vaping机器人”，它是完全计算机化的， 使用flexiWare软件（inExpose，SCIREQ，Montreal）可编程，仅用于鼻递送给啮齿动物， 最近描述的SARS-CoV-2介导的肺损伤的仓鼠模型。电子烟的暴露将是 在科罗拉多大学安舒茨医学院（丹佛）进行，并在短暂的运输后， COVID-19模型将在科罗拉多州立大学（CSU）的BSL 3设施（英尺）完成。柯林斯，CO）。那里我们 将监测仓鼠长达7天，研究气道/肺组织病理学和ACE 2/ACE表达 尸检后。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、病毒学和新兴病原体。我们将更好地了解机制 吸烟者的COVID-19恶化，以及潜在的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.