Document text
Principal Investigator: Mohamed Abdel Mohsen
Organization: RUSH UNIVERSITY MEDICAL CENTER
Fiscal Year: 2021
Award: $215,870
Funding agency: National Institute on Alcohol Abuse and Alcoholism
PROJECT SUMMARY
Recent data show that 10-30% of coronavirus disease 2019 (COVID-19) patients do not fully recover and suffer
from a wide range of symptoms that persist after the SARS-CoV-2 infection has been cleared (so-called post-
COVID-19 syndrome or Long Hauler). Severe COVID-19 and associated risk factors appear to increase the risk
of developing post-COVID-19 syndrome and yet a substantial number of patients without known risk factors also
develop post-COVID-19 syndrome. Thus, additional risk factors leading to post-COVID-19 syndrome must exist.
One potential risk factor is excessive alcohol consumption. (1) Alcohol is the most frequently used drug in the
United States, and alcohol use increases during public health crises, especially in socioeconomic disadvantaged
communities. (2) Alcohol results in inappropriate immune responses to pathogens. (3) Alcohol disrupts intestinal
and lung barrier integrity which can further promote inflammation. We recently showed that increased serum
Zonulin (a marker of disrupted intestinal barrier integrity) and increased endotoxin (LBP) are associated with
inflammation during COVID-19 and can predict disease severity and mortality. Accordingly, we hypothesize
that: (a) there is a bidirectional interaction between alcohol misuse and SARS-CoV-2 infection leading to
increased risk of post-COVID-19 syndrome in patients with alcohol use disorder (AUD) and more severe AUD
in COVID-19 patients; and (b) the underlying mechanism of these interactions is microbiota dysbiosis and/or
disruption of intestinal barrier integrity, promoting inflammation and dysregulated immune-responses to the virus.
To test our hypotheses, we will leverage our NIAAA supported COVID-19 supplement at Rush University Medical
Center (RUMC), which is actively following more than 7,000 SARS-CoV-2 positive patients and 2,000 SARS-
CoV-2 negative patients over 12 months using structured questionnaires. All patients are screened for alcohol
use/misuse. Furthermore, we will recruit a subset of patients to provide biological samples to test our mechanistic
hypothesis evaluating the link between AUD, post-COVID-19 syndrome, and gut-derived inflammation. In Aim
1, we will test the hypothesis that AUD increases the risk and severity of post-COVID-19 syndrome by
promoting gut-derived inflammation. (1a) We will determine if increased alcohol use/misuse is associated
with risk and severity of post-COVID-19 syndrome. (1b) We will elucidate the role of gut-derived inflammation in
AUD promotion of the post-COVID-19 syndrome by interrogating stool microbiota composition/function, systemic
markers of intestinal barrier integrity, inflammation, and immune activation. In Aim 2, we will test the
hypothesis that COVID-19 increases the risk and severity of AUD and alcohol-induced intestinal barrier
disruption. (2a) we will determine whether post-COVID-19 syndrome is associated with increased risk of AUD.
(2b) We will determine if COVID-19 decreases resilience of intestinal barrier to the damaging effects of alcohol
which would result in increased risk of alcohol-induced intestinal leak that could lead to organ damage using
organoids generated from individuals with and without post-COVID-19 and/or AUD.
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mortality><COVID19 death><COVID19 fatality><COVID19 induced death><COVID19 induced fatality><COVID19 induced mortality><COVID19 infection><COVID19 mortality><COVID19 negative><COVID19 patient><COVID19 positive patient><COVID19 related death><COVID19 related fatality><COVID19 related mortality><COVID19 virus><CV-19><CV19><Cause of Death><Chronic><CoV disease><CoV-2><CoV2><Cohort Studies><Communities><Concurrent Studies><Critical Illness><Critically Ill><Da Nang Lung><Data><Development><Diabetes Mellitus><Drug usage><Endotoxins><Enrollment><EtOH drinking><EtOH use><Feces><GI microbiome><Goals><Heavy Drinking><Hypertension><Immune Cell Activation><Immune response><Immunological response><Individual><Infection><Inflammation><Inflammatory><Intestinal><Intestinal Leakage><Intestines><Knowledge><LPS-binding protein><Lead><Leaky Gut><Link><Long COVID><Long COVID-19><Long coronavirus disease><Long coronavirus disease 2019><Longitudinal Studies><Lung><Lung Respiratory System><Machine Learning><Mediating><Morbidity><Morbidity - disease rate><NIAAA><National Institute on Alcohol Abuse and Alcoholism><Obesity><Organ><Organoids><Patients><Pattern><Pb element><Pneumonia><Post Acute Sequelae of COVID19><Post Acute Sequelae of SARS-CoV-2><Post Acute Sequelae of SARS-CoV2><Post Acute Sequelae of severe acute respiratory syndrome coronavirus 2><Post-Acute Sequelae of SARS-CoV-2 Infection><Predisposition><Public Health><QOL><Quality of life><Questionnaires><Recovery><Risk><Risk Factors><Role><SARS corona virus 2><SARS-CoV-2><SARS-CoV-2 associated death><SARS-CoV-2 associated fatality><SARS-CoV-2 associated mortality><SARS-CoV-2 death><SARS-CoV-2 fatality><SARS-CoV-2 induced death><SARS-CoV-2 induced fatality><SARS-CoV-2 induced mortality><SARS-CoV-2 infected patient><SARS-CoV-2 infection><SARS-CoV-2 mortality><SARS-CoV-2 negative><SARS-CoV-2 patient><SARS-CoV-2 positive patient><SARS-CoV-2 related death><SARS-CoV-2 related fatality><SARS-CoV-2 related mortality><SARS-CoV2><SARS-CoV2 infection><SARS-associated corona virus 2><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-related corona virus 2><SARS-related coronavirus 2><SARSCoV2><Sampling><Serum><Severe Acute Respiratory Distress Syndrome CoV 2><Severe Acute Respiratory Distress Syndrome Corona Virus 2><Severe Acute Respiratory Distress Syndrome Coronavirus 2><Severe Acute Respiratory Syndrome CoV 2><Severe Acute Respiratory Syndrome-associated coronavirus 2><Severe Acute Respiratory Syndrome-related coronavirus 2><Severe acute respiratory syndrome associated corona virus 2><Severe acute respiratory syndrome corona virus 2><Severe acute respiratory syndrome coronavirus 2><Severe acute respiratory syndrome coronavirus 2 infection><Severe acute respiratory syndrome related corona virus 2><Severities><Severity of illness><Shock Lung><Socioeconomically disadvantaged><Stiff lung><Structure><Susceptibility><Symptoms><Testing><TimeLine><United States><University Medical 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2><design><designing><developmental><diabetes><digestive tract microbiome><disease severity><drink heavily><drug use><dysbacteriosis><dysbiosis><dysbiotic><enroll><enteric microbiome><ethanol consumption><ethanol drinking><ethanol effect><ethanol ingestion><ethanol intake><ethanol misuse><ethanol product use><ethanol use><ethanol use disorder><excessive alcohol consumption><excessive alcohol ingestion><excessive alcohol intake><excessive drinking><excessive ethanol ingestion><extreme drinking><fatality due to COVID-19><fatality due to COVID19><fatality due to SARS-CoV-2><fatality due to coronavirus disease 2019><fatality due to severe acute respiratory syndrome coronavirus 2><gastrointestinal microbiome><gut inflammation><gut microbiome><gut-associated microbiome><hCoV19><heavy alcohol use><heavy metal Pb><heavy metal lead><high blood pressure><high risk><host response><human disease><hyperpiesia><hyperpiesis><hypertensive disease><immune activation><immune system function><immune system response><immunoresponse><infected with COVID-19><infected with COVID19><infected with SARS-CoV-2><infected with SARS-CoV2><infected with coronavirus disease 2019><infected with severe acute respiratory syndrome coronavirus 2><inflammatory disease of the intestine><inflammatory disorder of the intestine><intestinal autoinflammation><intestinal barrier><intestinal biome><intestinal inflammation><intestinal microbiome><intestinal mucosal barrier><learning classifier><life-threatening COVID><life-threatening COVID-19><life-threatening SARS-CoV-2><life-threatening coronavirus disease><life-threatening coronavirus disease 2019><life-threatening severe acute respiratory syndrome coronavirus 2><lipopolysaccharide-binding protein><long haul COVID><long haul COVID-19><long haul coronavirus disease><long haul coronavirus disease 2019><long haul sequelae of COVID-19><long haul sequelae of coronavirus disease 2019><long hauler><long-hauler syndrome><long-term COVID><long-term 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infected with COVID><patient infected with COVID-19><patient infected with SARS-CoV-2><patient infected with coronavirus disease><patient infected with coronavirus disease 2019><patient infected with severe acute respiratory syndrome coronavirus 2><patient screening><patient subgroups><patient subpopulations><patient subsets><patient subtypes><patient with COVID><patient with COVID-19><patient with COVID19><patient with SARS-CoV-2><patient with coronavirus disease><patient with coronavirus disease 2019><patient with severe acute respiratory distress syndrome coronavirus 2><phosphatidylethanol><post COVID syndrome><post COVID-19 syndrome><post acute COVID syndrome><post acute COVID-19><post acute COVID-19 syndrome><post acute SARS-CoV-2><post acute coronavirus disease 2019><post acute coronavirus disease 2019 syndrome><post acute coronavirus disease syndrome><post acute severe acute respiratory syndrome coronavirus 2><post coronavirus disease 2019 syndrome><post coronavirus disease syndrome><post-acute sequelae following SARS-CoV-2 infection><post-acute sequelae of COVID-19><post-acute sequelae of coronavirus disease 2019><prevent><preventing><pulmonary><recruit><resilience><response><serious COVID><serious COVID-19><serious SARS-CoV-2><serious coronavirus disease><serious coronavirus disease 2019><serious severe acute respiratory syndrome coronavirus 2><severe COVID><severe COVID-19><severe COVID19><severe SARS-CoV-2><severe acute respiratory syndrome coronavirus 2 associated death><severe acute respiratory syndrome coronavirus 2 associated fatality><severe acute respiratory syndrome coronavirus 2 associated mortality><severe acute respiratory syndrome coronavirus 2 death><severe acute respiratory syndrome coronavirus 2 fatality><severe acute respiratory syndrome coronavirus 2 induced death><severe acute respiratory syndrome coronavirus 2 induced fatality><severe acute respiratory syndrome coronavirus 2 induced mortality><severe acute respiratory syndrome coronavirus 2 infected patient><severe acute respiratory syndrome coronavirus 2 mortality><severe acute respiratory syndrome coronavirus 2 negative><severe acute respiratory syndrome coronavirus 2 patient><severe acute respiratory syndrome coronavirus 2 positive patient><severe acute respiratory syndrome coronavirus 2 related death><severe acute respiratory syndrome coronavirus 2 related fatality><severe acute respiratory syndrome coronavirus 2 related mortality><severe coronavirus disease><severe coronavirus disease 19><severe coronavirus disease 2019><severe severe acute respiratory syndrome coronavirus 2><social role><socio-economic disadvantage><socio-economically disadvantaged><socio-economically underprivileged><socioeconomic disadvantage><socioeconomically underprivileged><stool><symptom association><symptom comorbidity><unhealthy alcohol use><wet lung><zonulin>