Exosome microRNAs may hold key to understanding COVID-19 inflammation

Medical News: A team of researchers has made groundbreaking discoveries about the role of microRNAs (miRNAs) in COVID-19. They investigated how specific miRNAs enclosed in exosomes, tiny vesicles released by cells, are linked to inflammation and the progression of the disease. This Medical News report dives into the study, which focuses on four key miRNAs: miRNA-21, miRNA-218, miRNA-155, and miRNA-10b. These molecules may influence the severity of COVID-19 by affecting inflammation and processes like the epithelial-mesenchymal transition (EMT), a biological mechanism where epithelial cells transform into mesenchymal cells, contributing to tissue invasion. Understanding these miRNAs could help in early diagnosis and potentially guide treatment strategies.


Exosome microRNAs may hold key to understanding COVID-19 inflammation

What Are MicroRNAs and Exosomes?
MicroRNAs are small non-coding RNAs that regulate gene expression. They play a role in fundamental processes such as cell growth, immune response, and inflammation. In COVID-19, these miRNAs become particularly important because they may influence how the virus interacts with the body’s immune system.

Exosomes are small, membrane-bound vesicles that cells use to communicate with one another. They carry proteins, lipids, and nucleic acids, including miRNAs. In the context of COVID-19, the researchers focused on serum-derived exosomes - those found in blood - since they transport miRNAs that can promote inflammation and the EMT process.
 
The Study Approach
The research team collected blood samples from 30 COVID-19 patients and five healthy individuals to serve as controls. These patients were carefully chosen to ensure they did not have any pre-existing conditions like diabetes or hypertension, which could skew the results. The serum was separated from the blood, and exosomes were purified for analysis. Using real-time polymerase chain reaction (PCR) techniques, the researchers measured the relative expression levels of miRNA-21, miRNA-218, miRNA-155, and miRNA-10b.
 
The key goal was to observe how these miRNAs behave in COVID-19 patients compared to healthy individuals. Their increased expression might explain how the virus exacerbates inflammation, contributing to severe symptoms like acute respiratory distress syndrome (ARDS).
 
Key Findings
-miRNA-21
The study found that miRNA-21 levels were significantly higher in COVID-19 patients. This miRNA has been associated with various inflammatory conditions, such as osteoarthritis and colitis, as well as several types of cancer, including breast and colon cancer. In COVID-19, the rise in miRNA-21 levels could explain the excessive inflammatory responses seen in severe cases, such as the "cytokine storm." Cytokine storms are dangerous immune responses where the body releases an overwhelming amount of pro-inflammatory cytokines, leading to complications like ARDS.
 
The research also suggests that miRNA-21 might be linked to tiss ue fibrosis, especially in the lungs, a common complication in severe COVID-19 cases. Fibrosis occurs when excess tissue builds up due to chronic inflammation, making it harder for organs to function properly.
 
-miRNA-218
The study also highlighted a significant increase in miRNA-218 levels in COVID-19 patients. Previous studies have shown that this miRNA plays a role in inhibiting immune responses, particularly by reducing the production of interferon, a key antiviral protein. This suppression could give the virus an advantage, allowing it to evade the immune system more effectively.
 
In addition to its role in immune suppression, miRNA-218 is also involved in inflammatory processes. The researchers believe this miRNA could contribute to the widespread inflammation seen in COVID-19, potentially making it a target for future therapies.
 
-miRNA-155
miRNA-155 is another miRNA known for its involvement in inflammation. The study found a significant increase in miRNA-155 in the exosomes of COVID-19 patients. This miRNA is well-known for promoting inflammation by regulating the production of various cytokines. Its elevated levels could be driving the severe inflammatory responses in COVID-19, particularly in patients with ARDS.

Interestingly, miRNA-155 has also been implicated in the EMT process, which is often linked to cancer metastasis. In COVID-19, its role in EMT could explain some of the more severe complications, such as lung damage and multi-organ failure.
 
-miRNA-10b
While the increase in miRNA-10b was not as pronounced as the other three miRNAs, it still showed a significant elevation in COVID-19 patients compared to healthy individuals. miRNA-10b is associated with the EMT process, especially in cancers such as breast cancer, where it promotes metastasis. Its involvement in COVID-19 could be similar, possibly contributing to tissue damage and fibrosis.
 
Hypoxia and MicroRNA Expression
One of the study’s interesting observations was the correlation between low blood oxygen levels (hypoxia) and elevated miRNA expression. In COVID-19 patients with oxygen saturation levels below 90.6%, the expression of miRNA-21, miRNA-218, and miRNA-155 was significantly higher. This suggests that these miRNAs might be involved in worsening the hypoxic conditions in COVID-19 patients, potentially leading to more severe inflammation and tissue damage.
 
Clinical Implications and Future Research
The findings from this study suggest that miRNA-21, miRNA-218, miRNA-155, and miRNA-10b play a significant role in the pathogenesis of COVID-19. Their elevated levels in serum-derived exosomes could be used as biomarkers to help identify severe cases of the disease early on. Moreover, targeting these miRNAs could provide new therapeutic strategies for managing COVID-19, particularly in preventing the progression of the disease to severe inflammatory stages.
 
Given that these miRNAs are also involved in the EMT process, future research could explore how they contribute to long-term complications, such as lung fibrosis and organ damage. Additionally, further studies are needed to determine whether inhibiting these miRNAs can reduce inflammation and improve outcomes for COVID-19 patients.
 
Conclusion
The study provides strong evidence that miRNA-21, miRNA-218, miRNA-155, and miRNA-10b are significantly upregulated in COVID-19 patients, particularly those with severe inflammatory symptoms. These miRNAs likely play a role in driving inflammation, immune suppression, and tissue damage in COVID-19. As the world continues to battle the pandemic, understanding these molecular mechanisms could open the door to new treatments and diagnostic tools. The research team emphasizes the importance of continuing to explore miRNA-based therapies to combat the long-term effects of COVID-19.
 
The study findings were published in the peer-reviewed journal: Heliyon.
https://www.sciencedirect.com/science/article/pii/S2405844024153340
 
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https://www.thailandmedical.news/news/new-study-reveals-key-differences-in-mirna-expression-between-long-covid-and-recovered-patients