Alcohol Misuse: An Independent Risk Factor that Increases the Incidence and Severity of COVID-19

酗酒：增加 COVID-19 发病率和严重程度的独立风险因素

• 批准号: 10163399
• 负责人: ALI KESHAVARZIAN
• 金额: $ 31.39万
• 依托单位: RUSH UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-07-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10163399
• 关键词: 2019-nCoV; 3-nitrotyrosine; Academic Medical Centers; Address; Admission activity; Adult Respiratory Distress Syndrome; Age; Alcohol consumption; Alcohols; Anxiety; COVID-19; COVID-19 pandemic; Cause of Death; Cessation of life; Circadian Rhythms; Circadian desynchrony; Clinical; Coughing; Critical Illness; Cross-Sectional Studies; Data; Desire for food; Diagnosis; Disease; Drug usage; Emergency department visit; Endothelium; Epithelial; Epithelium; Ethanol toxicity; Evaluation; Fever Chills; Fibrin fragment D; Flow Cytometry; Food; Functional disorder; Future; Habits; Health; Hospitals; Immune; Immune response; Immune system; Incidence; Individual; Infection; Inflammation; Inflammatory Response; Informatics; Interleukin-6; Intestines; Kidney; Lead; Liver diseases; Longitudinal Studies; Lung; Lung diseases; Machine Learning; Measures; Mediating; Mental Depression; Minority; Morbidity - disease rate; Obesity; Organ; Outcome; Oxidative Stress; Pathology; Patients; Pattern; Peripheral Blood Mononuclear Cell; Physicians; Plasma; Pneumonia; Prevention; Proteins; Public Health; Quality of life; Questionnaires; Race; Recommendation; Recovery; Risk; Risk Factors; Role; Serum; Severities; Severity of illness; Shortness of Breath; Signal Transduction; Sleep; Smell Perception; Smoking; Societies; Socioeconomic Status; Stress; Stressful Event; Structure; Swab; Symptoms; Taste Perception; Testing; Therapeutic Intervention; United States; Virus; alcohol effect; alcohol misuse; alcohol response; alcohol screening; alcohol use disorder; associated symptom; biobank; circadian; comorbidity; cytokine; cytokine release syndrome; design; dysbiosis; flu; gut microbiome; immune system function; intestinal barrier; learning classifier; lifestyle factors; longitudinal analysis; low socioeconomic status; mortality; pathogen; patient subsets; resilience; response; socioeconomics; soluble RAGE; therapeutic target; tissue injury; zonulin

ABSTRACT The coronavirus disease 2019 (COVID-19) pandemic has resulted in unprecedented morbidity and mortality. Risk factors like age, obesity, and comorbidity impact the rate of SARS-CoV-2 infection and severity of COVID- 19 leading to hospital ICU admission and death. Additional risk factors that promote exaggerated immune and inflammatory response to the virus leading to severe disease or death must exist. One such risk factor could be alcohol consumption because: (1) Alcohol is the most frequently used drug in the United States. (2) Patients hospitalized for pneumonia who have an alcohol use disorder (AUD) are at greater risk for developing Acute Respiratory Distress Syndrome (ARDS) (the primary cause of death in COVID-19) than non-AUD patients; and (3) Alcohol negatively impacts function of the immune system and results in an inappropriate response to pathogens (a primary mechanism of severe COVID-19 and ARDS); and (4) Alcohol disrupts the intestinal microbiome (dysbiosis) and intestinal and lung barriers which can both further promote inflammation and contribute to ARDS. Accordingly, we hypothesize that alcohol misuse is an independent risk factor that increases the incidence and severity of COVID-19 by promoting exaggerated and dysregulated immune- inflammatory responses to SARS-CoV-2. We will leverage our COVID-19 data and biorepository at Rush University Medical Center (RUMC), which has tested over 22,000 patients (68% minority) with over 6000 patients testing positive, over 1000 hospitalized, over 600 critically ill. Currently, all patients arriving at RUMC are screened for alcohol use with AUDIT. Our COVID-19 biorepository has banked nasopharyngeal swabs, serum/plasma, and peripheral blood mononuclear cells (PBMC). We will address the following Specific Aims: Aim 1: Determine if alcohol use or misuse increases severity of COVID-19 and elucidate interactions with other risk factors. In this cross sectional study, we will use a machine learning classifier to determine if increased alcohol use/misuse are associated with more severe clinical presentation and poorer COVID-19 health outcomes (in 12,000 RUMC, 6000 COVID-19+) patients. Aim 2. Determine the impact of alcohol use and misuse on COVID-19 disease course and the impact of COVID-19 on alcohol consumption. In this longitudinal study, we will conduct longitudinal analysis of alcohol use in 6000 patients positive for COVID-19 to determine: (2a) if alcohol use/misuse is associated with slower recovery from COVID-19-associated symptoms. Aim 3. Determine if alcohol misuse results in exaggerated immune-inflammatory response to SARS-CoV-2 infection and more organ dysfunction in COVID-19 patients and explore the mechanisms. In this mechanistic Aim, we will compare COVID-19 patients with different disease severity to determine if alcohol misuse is associated with: (3a) altered immune/inflammatory response. (3b) disrupted intestinal barrier integrity. We will use machine learning and other advanced informatics approaches to investigate these Aims to discover new mechanisms for alcohol-COVID-19 interactions for prevention and therapeutic targets for COVID-19.

抽象的 2019年冠状病毒病（Covid-19）大流行导致了前所未有的发病率和死亡率。 年龄，肥胖和合并症等危险因素会影响SARS-COV-2感染的发生率以及COVID的严重程度 19导致医院ICU入院和死亡。促进夸张免疫和的其他风险因素 对导致严重疾病或死亡的病毒的炎症反应必须存在。一个这样的风险因素可能 饮酒是因为：（1）酒精是美国最常用的药物。 （2）患者 患有饮酒障碍（AUD）的肺炎住院 呼吸窘迫综合征（ARDS）（COVID-19的主要原因）比非aud患者；和 （3）酒精会对免疫系统的功能产生负面影响，并导致对 病原体（严重的COVID-19和ARDS的主要机制）； （4）酒精破坏肠道 微生物组（营养不良）和肠壁和肺屏障，这既可以进一步促进炎症，又可以 促成ards。因此，我们假设滥用酒精是一个独立的危险因素 通过促进夸张和失调的免疫 - 对SARS-COV-2的炎症反应。我们将利用Rush的Covid-19数据和生物库 大学医学中心（RUMC），已测试了22,000多名患者（68％的少数民族） 测试阳性的患者，超过1000例住院，有600多名重病。目前，所有到达RUMC的患者 通过审核进行筛选以饮酒。我们的COVID-19生物座位已将鼻咽拭子融为一体， 血清/血浆和外周血单核细胞（PBMC）。我们将解决以下具体目标： AIM 1：确定酒精使用或滥用是增加了COVID-19的严重程度并阐明相互作用 与其他风险因素。在这项横截面研究中，我们将使用机器学习分类器来确定是否是否 饮酒/滥用的增加与更严重的临床表现和较差的covid-19有关 健康结果（12,000名RUMC，6000名Covid-19）患者。目标2。确定饮酒的影响 以及滥用Covid-19疾病课程以及Covid-19对饮酒的影响。在这个 纵向研究，我们将对6000名Covid-19的患者进行酒精使用的纵向分析 确定：（2a）如果酒精使用/滥用与从COVID相关的恢复较慢有关 症状。目标3。确定滥用酒精是否会导致免疫炎症反应夸大 在199位患者中进行SARS-COV-2感染和更多器官功能障碍，并探索 机制。在这种机械目的中，我们将比较疾病严重程度不同的Covid-19患者 确定滥用酒精是否与：（3A）免疫/炎症反应改变。 （3b）中断 肠壁完整性。我们将使用机器学习和其他高级信息学方法 调查这些目的是发现针对酒精 - 葡萄球菌相互作用的新机制，以预防和 COVID-19的治疗靶标。