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COVID\u201019 superimposed on underlying liver disease notably worsens the outcome of many forms of liver injury. The goal of a current pilot study was to test the dual exposure of alcohol and COVID\u201019 infection in an experimental animal model of alcohol\u2010associated liver disease (ALD).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>After 4\u2009weeks of ethanol (EtOH) feeding, C57BL\/6 male mice received SARS\u2010CoV\u20102 (SARS2\u2010N501Y<jats:sub>MA30<\/jats:sub>) intranasally at 3\u2009\u00d7\u200910<jats:sup>2<\/jats:sup>, 1\u2009\u00d7\u200910<jats:sup>3<\/jats:sup>, 3\u2009\u00d7\u200910<jats:sup>3<\/jats:sup>, and 1\u2009\u00d7\u200910<jats:sup>4<\/jats:sup> plaque\u2010forming units (PFU). Mice were then weighed\/monitored daily for morbidity\/mortality for 10\u2009days while continuing EtOH consumption. Markers of liver inflammation, injury, and intestinal barrier integrity were evaluated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A similar gradual weight loss was observed in all inoculated mice (slightly less in the 3\u2009\u00d7\u200910<jats:sup>2<\/jats:sup> group) up to post\u2010infection day 4. Greater mortality was observed in mice receiving the highest viral dose at days 3 and 4 post\u2010infection. The majority of the surviving mice subjected to EtOH and inoculated with 3\u2009\u00d7\u200910<jats:sup>3<\/jats:sup> or 1\u2009\u00d7\u200910<jats:sup>4<\/jats:sup> PFU rapidly lost 25% of their body weight and were euthanized on post\u2010infection day 4. Analysis of liver health in animals that survived to the end of the experiment exhibited no significant changes in hepatic steatosis but had a limited increase in plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels at all viral doses versus EtOH alone. However, the 1\u2009\u00d7\u200910<jats:sup>4<\/jats:sup> PFU viral dose exacerbated EtOH\u2010induced hepatic inflammation characterized by elevated levels of several pro\u2010inflammatory cytokines, including <jats:italic>Il\u20106<\/jats:italic> and <jats:italic>Tnf\u2010\u03b1<\/jats:italic>. There was limited effect of viral infection on the intestine.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>SARS\u2010CoV\u20102 infection caused a dose\u2010dependent negative impact on body weight and survival in mice fed EtOH. This pilot study suggests that early mortality observed after high\u2010dose SARS\u2010CoV\u20102 challenge could be due, in part, to hepatic dysfunction following chronic EtOH feeding.<\/jats:p><\/jats:sec>","DOI":"10.1111\/acer.15528","type":"journal-article","created":{"date-parts":[[2025,1,6]],"date-time":"2025-01-06T04:55:26Z","timestamp":1736139326000},"page":"587-598","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Impact of chronic ethanol consumption and <scp>SARS<\/scp>\u2010<scp>COV<\/scp>\u20102 on the liver and intestine: A pilot dose\u2013response study in mice"],"prefix":"10.1111","volume":"49","author":[{"given":"Smita","family":"Ghare","sequence":"first","affiliation":[{"name":"Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, School of Medicine University of Louisville  Louisville Kentucky 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