Chronic ethanol consumption dysregulates innate immune response to SARS-CoV-2 infection in the lungs - NHP

Alcohol consumption is widespread with over half of the individuals over 18 years of age in the U.S. reporting alcohol use in the last 30 days. Moreover, 9 million Americans engaged in binge or chronic heavy drinking (CHD) in 2019. CHD negatively impacts the pathogen clearance and tissue repair thus increasing susceptibility to infection. Therefore, it has been hypothesized that chronic alcohol consumption negatively impacts COVID-19 outcomes; however, the interplay between chronic alcohol use and SARS-CoV-2 infection has yet to be elucidated. Therefore, in this study we investigated the impact of chronic alcohol consumption on SARS-CoV-2 anti-viral responses in bronchoalveolar lavage samples (BAL) from humans and rhesus macaques. Our data how that in both humans and macaques, the induction of key antiviral cytokines and growth factors such as IFN-b was decreased with ethanol consumption. Indeed, more differentially expressed genes (DEG) mapped to Gene Ontology (GO) terms associated with antiviral immunity following SARS-CoV-2 infection of in macrophages following 6 month of ethanol consumption. In contrast, TLR signaling pathways were increased after 6 months of ethanol consumption, indicative of aberrant inflammation responses and reduced antimicrobial responses.