Synergistic Detrimental Effects of Cigarette Smoke, Alcohol, and SARS-CoV-2 in COPD Bronchial Epithelial Cells

Abstract

Lung conditions such as COPD, as well as risk factors such as alcohol misuse and cigarette smoking, can exacerbate COVID-19 disease severity. Synergistically, these risk factors can have a significant impact on immunity against pathogens. Here, we studied the effect of a short exposure to alcohol and/or cigarette smoke extract (CSE) in vitro on acute SARS-CoV-2 infection of ciliated human bronchial epithelial cells (HBECs) collected from healthy and COPD donors. We observed an increase in viral titer in CSE- or alcohol-treated COPD HBECs compared to untreated COPD HBECs. Furthermore, we treated healthy HBECs accompanied by enhanced lactate dehydrogenase activity, indicating exacerbated injury. Finally, IL-8 secretion was elevated due to the synergistic damage mediated by alcohol, CSE, and SARS-CoV-2 in COPD HBECs. Together, our data suggest that, with pre-existing COPD, short exposure to alcohol or CSE is sufficient to exacerbate SARS-CoV-2 infection and associated injury, impairing lung defences.

COVID-19 and smoking: Considerations after two years

“…Importantly, Muralidharan et al. studied the acute impact of short exposure to cigarette smoke extract and/or alcohol on SARS-CoV-2 infection of ciliated human bronchial epithelial cells of healthy subjects [19] , and found that viral titers were only increased in cells treated with both compounds but not with cigarette smoke extract or alcohol alone, thus emphasizing that cigarette smoke may only play a subsidiary role in the pathogenesis of COVID-19. Accordingly, the biological evidence that cigarette smoke alone would enhance the risk of infection and/or unfavorable disease progression remains weak, at best.…”