Healthy people who develop serious complications following infection with respiratory viruses, such as influenza, RSV or COVID, produce very high amounts of an enzyme protein involved in metabolism lipids: an intriguing biochemical discovery, which could make it possible to quickly identify high-risk patients and improve their survival rate.
Infections with the main circulating respiratory viruses (influenza, RSV and more recently COVID) are generally quite mild, but can nevertheless be much more dangerous for certain people at risk, notably the elderly and those affected by other diseases (comorbidities).
These serious infections are caused by major disruptions in the immune response, particularly the creation of a cytokine storm (hypercytokinemia) which can lead to significant lung damage and death in infected individuals.
Cytokines are important molecules secreted into the blood and serve as molecular communicators between cells in the body, for the immune and inflammatory response.
Healthy, but still vulnerable
Although the majority of deaths associated with respiratory infections are observed in this population of people at higher risk, the fact remains that a significant proportion of cases of severe respiratory infections also affect healthy people, without any risk factors. apparent.
For example, in one study it was reported that among patients hospitalized due to influenza during the 2015-2016 season, more than 60% of them had no underlying illness (1).
There are therefore clearly other risk factors for severe infections which are independent of age or general health level.
Strongly increasing enzyme
In a large-scale study, bringing together researchers from around fifteen medical institutes around the world, we have just highlighted one of the main factors which could explain this mystery (2).
The researchers first analyzed blood samples taken from some people who died from H7N9 avian flu, which first spread to humans in 2013.
Comparing the samples with those from other people who had survived the infection, they (unsurprisingly) observed that the fatal cases had higher levels of inflammation caused by a “cytokine storm.”
It was further analysis of the genes expressed by patients upon admission to hospital that yielded the most surprising result: levels of an enzyme called oleoyl-ACP hydrolase (OLAH) were increased 82-fold. compared to survivors!
This dramatic increase in OLAH levels has also been noted for other types of viral lung infections.
For example, very sick (on ventilators) seasonal influenza patients have been observed to have much higher levels of OLAH than healthy controls.
OLAH expression levels were also elevated in patients with severe COVID-19 as well as in children hospitalized following respiratory syncytial virus (RSV) infection.
Lipid droplets
This important role of OLAH in the severity of viral infections is completely unexpected, because this enzyme participates in the synthesis of fatty acids and therefore has at first glance no link with the immune response to viruses.
However, researchers found that high levels of the enzyme caused an increase in lipid droplets in the blood which, in turn, overactivated immunity by simulating microbial infection and led to the excessive production of inflammatory cytokines.
It also appears that virus replication is greatly promoted by increased lipid production, which could obviously contribute to the severity of the infection.
The reason why some people have such high levels of OLAH expression remains unknown, but this phenomenon could serve as a biochemical biomarker to predict disease progression and help better manage early interventions (patient prioritization, ventilation artificial, steroid administration) in patients at risk of death.
In the longer term, these results also suggest that OLAH could constitute a target for the development of new therapies to protect against serious respiratory diseases. One more weapon in our war against these dreaded infections!
REFERENCES
(1) Puig-Barbera et coll. «Influenza epidemiology and influenza vaccine effectiveness during the 2015–2016 season: results from the Global Influenza Hospital Surveillance Network». BMC Infect. Dis. 2019; 19: 415.
(2) Jia X et coll. «High expression of oleoyl-ACP hydrolase underpins life-threatening respiratory viral diseases». Cell 2024; 187: 4586-4604.e20.
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