Impact of chronic ethanol consumption and SARS-COV-2 on the liver and intestine: A pilot dose-response study in mice

Background: During the coronavirus disease 2019 (COVID-19) pandemic, there was a marked increase in alcohol consumption. COVID-19 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-19 infection in an experimental animal model of alcohol-associated liver disease (ALD).

Methods: After 4 weeks of ethanol (EtOH) feeding, C57BL/6 male mice received SARS-CoV-2 (SARS2-N501Y_MA30) intranasally at 3 × 10², 1 × 10³, 3 × 10³, and 1 × 10⁴ plaque-forming units (PFU). Mice were then weighed/monitored daily for morbidity/mortality for 10 days while continuing EtOH consumption. Markers of liver inflammation, injury, and intestinal barrier integrity were evaluated.

Results: A similar gradual weight loss was observed in all inoculated mice (slightly less in the 3 × 10² group) up to post-infection day 4. Greater mortality was observed in mice receiving the highest viral dose at days 3 and 4 post-infection. The majority of the surviving mice subjected to EtOH and inoculated with 3 × 10³ or 1 × 10⁴ PFU rapidly lost 25% of their body weight and were euthanized on post-infection 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 × 10⁴ PFU viral dose exacerbated EtOH-induced hepatic inflammation characterized by elevated levels of several pro-inflammatory cytokines, including Il-6 and Tnf-α. There was limited effect of viral infection on the intestine.

Conclusions: SARS-CoV-2 infection caused a dose-dependent negative impact on body weight and survival in mice fed EtOH. This pilot study suggests that early mortality observed after high-dose SARS-CoV-2 challenge could be due, in part, to hepatic dysfunction following chronic EtOH feeding.