Chronic alcohol consumption dysregulates innate immune response to SARS-CoV-2 in the lung
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 U.S. Americans engaged in binge or chronic heavy alcohol use in 2019.
Chronic heavy alcohol use negatively impacts pathogen clearance and tissue repair, including in the respiratory tract, thereby increasing susceptibility to infection. Although, it has been hypothesized that chronic alcohol consumption negatively impacts COVID-19 outcomes; the interplay between chronic alcohol use and SARS-CoV-2 infection outcomes has yet to be elucidated.
In this study the researchers employed luminex, scRNA sequencing, and flow cytometry to investigate the impact of chronic alcohol consumption on SARS-CoV-2 anti-viral responses in bronchoalveolar lavage cell samples from humans with alcohol use disorder and rhesus macaques that engaged in chronic alcohol use.
Our data show that in both humans (n = 6) and macaques (n = 11), the induction of key antiviral cytokines and growth factors was decreased with chronic ethanol consumption.
Moreover, in macaques fewer differentially expressed genes mapped to Gene Ontology terms associated with antiviral immunity following 6 month of ethanol consumption while TLR signaling pathways were upregulated.
These data are indicative of aberrant inflammation and reduced antiviral responses in the lung with chronic alcohol consumption.
Research in context
Evidence before this study
Alcohol use disorder (AUD) impacts 8% of all adults in the United States. Clinical and experimental studies have shown that AUD interferes with anti-microbial responses and tissue repair resulting in increased susceptibility to infection.
Indeed, AUD has been implicated in increased severity of COVID-19; however, the exact mechanisms have yet to be elucidated.
Added value of this study
For this study, the researchers utilized a rhesus macaque model of voluntary ethanol self-administration to uncover the impact of chronic alcohol consumption on the acute response to SARS-CoV-2 infection.
This model accurately recapitulates human patterns of alcohol intake and immunological consequences.
The researchers report that macrophages are a prominent immune cell target of SARS-CoV-2 infection in the lung and that chronic alcohol consumption led to a heightened inflammatory response, but a dampened interferon stimulated gene expression response.
Implications of all the available evidence
Collectively, these findings provide evidence that chronic alcohol consumption leads to a heightened inflammatory state at baseline and dysregulates acute response to SARS-CoV-2, skewing it towards aberrant inflammatory outcomes and away from anti-viral responses.
Finally, the non-human primate model utilized in this study provides insight into pathophysiology of AUD and consequences on respiratory infection.