Alcohol misuse is an overlooked risk factor for severe COVID-19, according to a review of evidence

Chronic alcohol misuse including Alcohol Use Disorder (AUD), is an overlooked risk factor for severe or fatal COVID-19, according to a review of medical and scientific studies. The review, in Alcoholism: Clinical and Experimental Research, outlines growing evidence strongly implicating alcohol misuse in COVID-19 severity. The clinical manifestations of COVID-19, a coronavirus, are extremely variable, and research points to patients’ contrasting immune responses as a key driver of symptom severity.

Some people are known to be more vulnerable than others to severe COVID-19, including older adults (age 65+) and those with certain pre-existing health conditions, such as Type 2 diabetes, cardiovascular disease, chronic lung disease, and kidney disease. But plenty of patients who experience severe COVID-19, sometimes including death, do not fit into these categories, implying that additional risk factors are involved.

Studies have found that AUD is associated with severe COVID-19 disease and/or higher risk of mortality, especially in the elderly. Substance use disorders (SUDs) generally are linked to an increased risk of COVID-19 severity and of other underlying health conditions associated with worse COVID-19 outcomes. The COVID-19 pandemic has been characterized by eroded social support, socioeconomic struggles, and worsening mental health, contributing to increased alcohol sales and alcohol-related disease in the US and globally.

For the review, researchers evaluated data from studies on PubMed relating to alcohol misuse, COVID-19 severity, and factors and mechanisms involved in worse outcomes. In COVID-19, some patients’ immune systems fail to control the replication of the virus, leading to high viral levels.

The resulting exaggerated inflammatory response—a “cytokine storm”—triggers acute respiratory distress syndrome (ARDS). This severe form of lung injury is the most common cause of death in COVID-19. Increasing evidence implicates a certain inflammasome (a protein complex that induces inflammation to help clear the body of threats) called NLRP3.

Scientists have identified mechanisms by which alcohol misuse may impair the immune response to pathogens, especially in the lungs, and contribute to dangerous inflammatory responses. These help explain why AUD is a known risk factor for poor outcomes from viral diseases including HIV and Hepatitis C, and respiratory illnesses such as influenza and SARS.

Chronic alcohol use is almost uniformly associated with NLRP3 activation. Studies of people with chronic alcohol exposure and COVID-19 patients reveal the same systemic inflammation pathways, including inflammasome activation and amplified cytokine release.

Studies point to a plausible biological process. This relates to the gastrointestinal (GI) tract, a battleground for COVID-19 possibly second only to the lungs; GI symptoms in COVID-19 are linked to worse outcomes. The intestinal microbiome (micro-organisms in the gut) and the immune system appear closely intertwined.

Alcohol misuse and other underlying conditions that worsen COVID-19 share certain GI vulnerabilities: a pro-inflammatory microbiome in the gut (an intestinal imbalance) and “leaky gut” (abnormal intestinal permeability, allowing microbes to move into the blood). These two conditions combine to transfer gut bacteria to the lungs. That activates NLRP3, leading to systemic inflammation, manifesting as ARDS and more severe COVID-19.

The reviewers conclude that severe COVID-19 including death is clearly associated with AUD and SUD. Like aging and the pre-existing diseases known to increase COVID-19 risk, chronic alcohol exposure is associated with GI conditions and inflammasome hyperactivation triggering an outsized inflammatory state—realistic targets for treating severe COVID-19. There are no clear data yet on the impact of AUD on the effectiveness of COVID-19 vaccines.

More information:
Christopher B. Forsyth et al, Alcohol use disorder as a potential risk factor for COVID ‐19 severity: A narrative review, Alcoholism: Clinical and Experimental Research (2022). DOI: 10.1111/acer.14936

Journal information:
Alcoholism: Clinical and Experimental Research

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