Center for Circadian Rhythms and Alcohol-Induced Tissue Damage

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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.