Many risk factors for adverse outcomes in coronavirus disease 2019 (COVID-19) have been identified, including obesity, heart disease, and diabetes mellitus. Smoking involves aggravating or contributing to the disease process under various conditions, including infections.
A new prepress a medRxiv * The server reports the level of angiotensin 2 converting enzyme (ACE2) and furin, two enzymes that are closely related to infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19.
The ACE2 receptor
COVID-19 is a predominantly pneumonic condition, with most patients with terminal illnesses showing signs of acute respiratory failure. Often, however, this is related to multi-organ dysfunction with underlying vascular damage and thrombosis. The virus is thought to enter through the host membrane receptor, ACE2, which is found at elevated levels in the pulmonary epithelium. Among the various types of respiratory cells, type II pneumocytes, goblet cells, nasal epithelial and hair cells, and oral mucosal cells have the highest expression of this receptor.
ACE2 also has physiological activity, as it converts the vasoactive hormone angiotensin 2 into vasodilating metabolites, thus avoiding the harmful effects of the ancient molecule. Despite the intense focus on this receptor with the onset of the pandemic, it is still unclear as to the ACE2-induced change by the virus. There are two possibilities: either your activity is modulated or your expression is modified.
Smoking and risk of COVID-19
Several early reports have suggested that smokers have a lower risk of COVID-19, but this conclusion is suspicious, as there are more recent data. For example, a meta-analysis of 15 studies, including more than 2,400 people, showed that COVID-19 would likely be more severe and fatal in patients currently smoking. Another study showed that the rate of progression of COVID-19 is almost double in smokers compared to non-smokers.
The researchers attempted to identify a possible association between smoking and systemic inflammatory markers and between the sex of the individual and the expression of ACE2 and furin. It has been suggested that ACE2 levels are higher in the lungs of smokers, but this has not been studied in terms of the risk of development and severity of COVID-19.
The researchers obtained serum samples from patients with COVID-19 and those who had recovered from the infection, with a history of smoking and no history.
Smokers with COVID-19 have higher levels of inflammatory cytokines
Acute COVID-19 is known to be characterized by high levels of inflammatory mediators. Therefore, the current study examined 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 relative to controls without infection. Among patients with a history of smoking COVID-19, there was a marked increase in the production of certain specific cytokines, such as IFN-γ, 43 eotaxin, MCP-1, and IL-9, compared with those who did not smoke. . Interestingly, this latter subset of cytokines is associated with hyperactive inflammation, suggesting that smoking worsens the severity of COVID-19.
Smoking increases ACE2 levels in patients with COVID-19
The entry of SARS-CoV-2 into host cells is mediated by ACE2, which increased in the serum of patients with COVID-19 compared with controls. However, the researchers also found higher levels in the serum of patients with COVID-19 with a past or current smoking history, relative to controls (non-smokers). Men had higher ACE2 levels than women.
“Our results show that age and smoking status play a crucial role in governing COVID-19-related enzyme activity in human subjects.”
Smoking increases furin levels in COVID-19 patients who smoke
Serum furin levels were also higher in patients with COVID-19 with a history of smoking, as above, compared with non-smokers with COVID-19. Males showed a tendency to increase furin levels. Furin is a converting protein that is crucial for the mechanism of SARS-CoV-2 infection.
COVID-19 associated with changes in lipid profile
Lipid mediators, such as prostaglandins, are often altered during infections and can decrease or exaggerate the associated inflammation. The researchers showed the presence of a discriminating lipid profile between patients with COVID-19 and those who had recovered from the infection. Affected lipid markers include PGF2α, HETEs, LXA4, and LTB4, from the prostaglandin, hydroxyyeicosatetraenoic acid, lipoxin, and leukotriene pathways, respectively. However, smoking does not appear to be related to changes in these lipid pathways.
What are the implications?
Overall, the study shows that inflammatory molecules are significantly higher in smokers with COVID-19 relative to controls. The researchers also demonstrated an increase in cytokine and furin levels in patients with active COVID-19 relative to recovered patients.
These findings suggest the feasibility of developing these molecules as biomarkers to stratify patients with COVID-19 by disease severity, to optimize their management. As hospitals and healthcare systems around the world become more widespread, these types of biomarkers can help them prioritize care and resources by predicting more accurate disease outcomes.
The study suggests that COVID-19 is associated with a distinctive profile of markers and systemic inflammatory molecules that facilitate or mediate viral-host interactions. These are negatively affected by smoking, indicating a higher risk of poor outcomes among patients with COVID-19 who have a history of smoking.
Further research could lead to the effects of vaping and the perceived persistence of elevated ACE2 levels in recovered patients, which may underlie the “long-term” symptoms reported in many COVID-19 convalescents.
* Important news
medRxiv publishes preliminary scientific reports that are not peer-reviewed and therefore should not be considered conclusive, guide clinical practice / health-related behavior, or treated as established information.