Many risk factors for adverse outcomes in coronavirus 2019 (COVID-19) have been identified, including obesity, heart disease, and diabetes mellitus. Smoking is involved in reducing or contributing to the disease process in a number of conditions, including infections.
A new introduction to the medRxiv * server reporting angiotensin-converting enzyme 2 (ACE2) level and furin, two enzymes closely linked to infection with true respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent COVID-19.
The ACE2 receptor
COVID-19 in particular is a toxic condition, with the majority of patients with terminal illness showing signs of respiratory failure. Often, however, this is associated with multi-organ dysfunction with vascular damage and thrombosis. The virus is thought to invade the host membrane receptor, ACE2, which is found at high levels in the lung epithelium. Among the different types of respiratory cells, type II pneumocytes, goblet cells, nasal epithelial and ciliated cells, and cells of the oral mucosa are found to have the highest expression of this receptor.
ACE2 also has physical activity, as it converts the vasoactive hormone angiotensin 2 to vasodilatory metabolites, thus preventing the harmful effects of the old molecule. Despite the severity of this receptor with the onset of the pandemic, it is not yet clear how the virus altered ACE2. There are two possibilities: either its activity is modeled, or the expression is changed.
Risk of smoking and COVID-19
Several early reports have suggested that smokers will be at lower risk from COVID-19, but this decision is now being questioned, due to more recent data. For example, a meta-analysis of 15 studies, involving more than 2,400 individuals, showed that COVID-19 was more likely to be more severe and lethal in patients who currently smoke. Another study showed that the rate of COVID-19 progression is almost double in smokers compared to those in non-smokers.
The researchers focused on a possible link between smoking and systemic inflammation symptoms, and between the sex of the individual and the expression ACE2 and furin. ACE2 levels have been reported to be higher in smokers’ lungs, but this has not been studied in terms of developmental risk and severity of COVID-19.
The researchers obtained serum samples from patients with COVID-19 and those who had recovered from the disease, with and without a history of smoking.
Smokers with COVID-19 have higher levels of inflammatory cytokines
Acute COVID-19 is known to be characterized by high levels of inflammatory mediators. So the current study looked at 27 cytokines and chemokines.
They found that inflammatory cytokines such as IL-1α, IL-8, IL-2, VEGF and IL-10, were expressed at higher levels in patients with COVID-19 compared with controls without the disease. Among COVID-19 patients with a history of smoking, there was a significant increase in the production of specific cytokines, such as IFN-γ, 43 Eotaxin, MCP-1 and IL-9, compared with those who did not smoke. Interestingly, the latter subset of cytokines is associated with hyperactive inflammation, suggesting that smoking exacerbates COVID-19 depletion.
Smoking increases ACE2 levels in COVID-19 patients
SARS-CoV-2 uptake into host cells is mediated by ACE2, which was increased in serum of COVID-19 patients compared with the controls. However, the researchers also found higher serum levels of COVID-19 patients with a past or present history of smoking, compared to controls (non-smokers). Males had higher ACE2 levels than females.
“Our results show that age and smoking status play a critical role in regulating COVID-19-associated enzyme activity in human subjects.”
Smoking increases furin levels in COVID-19 patients who smoke
Serum furin levels were also higher in COVID-19 patients with a history of smoking, as above, compared with non-smokers with COVID-19. Males showed a move toward higher furin levels. Furin is a proprotein converter that is essential for engine for SARS-CoV-2 infection.
COVID-19 associated with changes in lipid profile
Lipid mediators such as prostaglandins are often altered during infections, and may reduce or exacerbate the associated inflammation. The researchers showed a lipid profile of discrimination among COVID-19 patients vs. those who recovered from the disease. The lipid markers affected include PGF2α, HETEs, LXA4 and LTB4 – from prostaglandin, hydroxyeicosatetraenoic acid, lipoxin and leukotriene pathways, respectively. However, smoking did not appear to be associated with changes in these lipid pathways.
What is the impact?
Overall, the study shows that inflammatory molecules are significantly higher in smokers with COVID-19 compared to controls. The researchers also showed higher levels of cytokines and furin in patients with active COVID-19 compared with recovered patients.
These findings suggest the potential for the development of these molecules as biomarkers to stabilize COVID-19 patients according to disease severity, in order to obtain optimal management. As hospitals and healthcare systems around the world continue to grow, these types of biomarkers can help them prioritize care and resources through more accurate prediction of disease outcomes.
The study suggests that COVID-19 is associated with a specific profile of systemic inflammatory signals and molecules that enable or mediate viral-host interactions. They are adversely affected by smoking, indicating a higher risk of adverse outcomes among COVID-19 patients with a history of smoking.
Further research could find out what the effect of vaping is and how high levels of ACE2 are thought to be present in recovered patients, which may underlie the symptoms of long-term slowdown. reported in many COVID-19 revivals.
* Important message
medRxiv publish preliminary scientific reports that are not peer-reviewed and, therefore, should not be seen as final, guiding health-related clinical practice / behavior, or be treated as information established.