Canadian Study Finds That Missing Platelet Enzyme Aggravates COVID-19 Inflammation and Triggers Disease Severity
Nikhil Prasad Fact checked by:Thailand Medical News Team Apr 12, 2025 20 hours, 9 minutes ago
Medical News: A new groundbreaking study by scientists from Université Laval in Canada has revealed how the absence of a specific platelet enzyme called 12-lipoxygenase (12-LOX) can make COVID-19 more dangerous by intensifying inflammation in the lungs and worsening overall disease severity. This
Medical News report details the surprising role of this enzyme in defending the body against SARS-CoV-2, the virus that causes COVID-19.
Canadian Study Finds That Missing Platelet Enzyme Aggravates COVID-19 Inflammation and
Triggers Disease Severity
The research was conducted by a collaborative team led by Ana Claudia dos S. P. Andrade, Éric Boilard, Nicolas Flamand, and Louis Flamand from the Centre de Recherche du CHU de Québec at Université Laval, along with experts from McGill University, Universidade Federal de Minas Gerais in Brazil, and Université de Montréal.
Platelets Are Not Just for Blood Clotting
Most people think of platelets as tiny cells in the blood that help form clots and stop bleeding. But in recent years, scientists have discovered that platelets do more than just that. They also play a crucial role in the body’s immune response by releasing signaling molecules that can either promote or reduce inflammation. These molecules include lipid-based substances called lipid mediators of inflammation (LMI), which are involved in both triggering and calming immune reactions.
One group of these mediators is made with the help of the enzyme 12-LOX, which converts fats in platelets into bioactive compounds like 12-hydroxyeicosatetraenoic acid (12-HETE) and 12-hydroxyeicosatrienoic acid (12-HETrE). These molecules were found to have anti-inflammatory effects, helping the body regulate inflammation caused by infections such as COVID-19.
The Experiment That Changed Everything
To understand how important 12-LOX is in COVID-19 infections, the scientists used genetically modified mice that lacked the enzyme. These mice were then infected with the SARS-CoV-2 virus. Compared to normal mice, those without the 12-LOX enzyme experienced much worse symptoms, with higher levels of inflammation in their lungs, more immune cells flooding into lung tissue, and significantly lower survival rates.
What was especially interesting is that the amount of 12-HETrE, a product of 12-LOX, was found to be inversely related to the severity of illness. In simple terms, the less of this compound the mice produced, the sicker they became. This strongly points to a protective role for 12-LOX and its byproducts in helping the body cope with the virus.
More Inflammation Without 12-LOX
The study didn’t stop at just observing symptoms. Using advanced technologies like RNA sequencing and lipid analysis, the researchers discovered that mice without 12-LOX showed abnormal gene expression in their lungs. Specifically, genes linked to inflammation and immune responses, such as
those related to the NLRP1 inflammasome, were disturbed.
Additionally, these mice showed altered lipid profiles in their lungs. The levels of helpful compounds like 12-HETrE and 12-HEPE (another anti-inflammatory lipid) were significantly lower, while other inflammatory compounds such as prostaglandins and thromboxane were elevated. These chemical imbalances contributed to a chaotic inflammatory environment in the lungs, leading to tissue damage, swelling, and reduced ability to fight the virus effectively.
Higher Death Rates and Lung Damage
When researchers examined lung tissues under a microscope, they found that mice without 12-LOX had severe lung injuries. These included thicker alveolar walls, heavy infiltration of white blood cells, and reduced air spaces needed for breathing. The lungs were filled with inflammatory cells like neutrophils, macrophages, and T-cells, especially by the third and fifth day after infection.
Moreover, the mice lacking the enzyme had worse survival outcomes. Almost all the mice in this group reached a point where they had to be euthanized due to disease severity, compared to significantly fewer deaths among the normal mice. This proved how vital 12-LOX is in protecting against lethal COVID-19 disease progression.
The Role of 12-HETrE as a Protective Compound
One of the key discoveries of this study is the role of 12-HETrE, which appears to act as a natural anti-inflammatory agent. When levels of this molecule were low, mice developed more severe lung inflammation and damage. This finding opens up the exciting possibility of using 12-HETrE or drugs that mimic its effects as new treatments for severe COVID-19 and possibly other inflammatory lung diseases.
The researchers also tested whether this effect was specific to COVID-19 or general to other viral infections. They infected mice lacking 12-LOX with the flu virus (H1N1) and found no major differences in disease progression compared to normal mice. This suggests that the harmful effects of 12-LOX deficiency are unique to SARS-CoV-2 and may be linked to the way the virus manipulates the body's immune and inflammatory systems.
Implications for Future Treatments
These findings shed new light on why some individuals develop severe COVID-19 despite having similar viral loads. It might not just be the virus but also how the body regulates inflammation that determines the outcome. The study strongly supports the idea of targeting lipid mediators and their associated enzymes as a potential strategy for treating severe cases of COVID-19.
By understanding how platelet-derived enzymes like 12-LOX protect against inflammation, doctors and researchers could develop drugs that either boost the enzyme’s activity or supplement the body with helpful molecules like 12-HETrE. This could offer a new line of defense for those who are at high risk of developing severe complications from COVID-19, including older adults and people with chronic illnesses.
Conclusion
This detailed study provides valuable insights into how the body’s own blood components, like platelets and their enzymes, help regulate inflammation during viral infections. The absence of the 12-LOX enzyme in platelets leads to a sharp rise in lung inflammation, severe tissue damage, and higher death rates in infected mice, even though their viral load remains unchanged. This means the enzyme plays a critical anti-inflammatory role during SARS-CoV-2 infection, likely by producing protective lipid molecules like 12-HETrE. The findings not only help us better understand the mechanisms behind severe COVID-19 but also point to new treatment strategies involving lipid mediators that could save lives in future pandemics.
The study findings were published in the peer reviewed journal: Proceedings of the National Academy of Sciences (PNAS).
https://www.pnas.org/doi/epub/10.1073/pnas.2420441122
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