Role of extracellular vesicles in COVID-19 inflammation

Medical News: A new study conducted by researchers from the Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas in Mexico City, alongside collaborators from Benemérita Universidad Autónoma de Puebla-Mexico, sheds light on how extracellular vesicles (EVs) derived from COVID-19 patients may contribute to inflammation and immune modulation. The study provides valuable insights into the potential mechanisms involved in the body’s immune response to the virus, offering a clearer understanding of the virus's impact on immune regulation. This Medical News report explores the study’s key findings and its implications for managing COVID-19’s inflammatory effects.


Role of extracellular vesicles in COVID-19 inflammation

What Are Extracellular Vesicles and Why Are They Important?
Extracellular vesicles (EVs) are small particles produced by cells that can carry molecular cargo such as RNA, proteins, and lipids. These particles play a crucial role in cell-to-cell communication and immune system regulation. In the context of viral infections, EVs can either help defend against pathogens or spread the infection to other cells. Previous studies have shown that EVs can carry viral components, contributing to immune responses and inflammation. This study focuses on how EVs derived from COVID-19 patients influence the body’s immune system, particularly in relation to inflammation.
 
Study Objectives
The researchers aimed to explore the differences between EVs that contain viral RNA and those that do not. They hypothesized that these two types of EVs would have different effects on the immune response, particularly in how they modulate the body’s reaction to inflammation.
 
The study examined EVs from 101 participants, including 61 patients with severe COVID-19, 20 with long COVID, and 20 healthy individuals. To assess the role of EVs in inflammation, the researchers used lipopolysaccharide (LPS), a substance known to stimulate the immune system, to trigger an inflammatory response in healthy blood samples. This model allowed the team to observe how EVs with and without viral RNA influence inflammation.
 
Key Findings on Viral RNA in EVs
Approximately half of the EVs from COVID-19 patients carried viral RNA, specifically genes E, RdRP, and N from the SARS-CoV-2 virus. Notably, the E gene sequences were the most common in these EVs, suggesting a possible role in immune modulation. Interestingly, despite severe symptoms in all patients, not all their EVs contained viral RNA. This finding suggests that the immune system may struggle to clear the infection in some patients, potentially contributing to prolonged inflammation and severe symptoms.
 
EVs were predominantly of myeloid origin, a type of white blood cell that plays a role in immune responses. These EVs displayed no significant differences between groups in terms of cell markers, but their RNA content varied significantly.
 
How EVs Influence t he Inflammatory Response
When the researchers exposed blood samples to EVs from COVID-19 patients, they discovered that the presence of viral RNA influenced the immune response differently than EVs without viral RNA. EVs that contained SARS-CoV-2 RNA (SARS-CoV2+) increased the production of interleukin-12 (IL-12), a protein associated with stimulating the immune system. On the other hand, these EVs decreased interleukin-13 (IL-13) production, a protein that helps control immune responses.
 
In contrast, EVs without viral RNA (SARS-CoV2-) increased the production of MIP-1α and IL-1β, two proteins involved in the body’s inflammatory response. These findings highlight that EVs with and without viral RNA have distinct effects on how the immune system responds to inflammation.
 
The Role of microRNAs in EVs
In addition to viral RNA, the study also explored the presence of microRNAs (miRNAs) in the EVs. MiRNAs are small molecules that regulate gene expression and play a critical role in the immune system. The researchers identified several miRNAs that were differentially expressed in EVs from COVID-19 patients.

Specifically, miR-19a-3p, miR-192-5p, and let-7c-5p were found in higher levels in EVs without viral RNA, while miR-92b-3p was lower in EVs containing viral RNA. These findings suggest that miRNAs carried by EVs may influence the body’s response to inflammation in COVID-19 patients.
 
Implications for COVID-19 Inflammation
The study’s results suggest that EVs play a significant role in regulating the immune response in COVID-19 patients. EVs containing viral RNA may inhibit certain aspects of the immune system, while EVs without viral RNA may promote inflammation through different pathways. This finding is crucial because understanding how EVs modulate immune responses could lead to better treatments for managing inflammation in COVID-19 patients.
 
The researchers also noted that long COVID patients had similar miRNA levels to healthy individuals, suggesting that the inflammatory effects of EVs may diminish over time as the body recovers from the virus. However, the presence of viral RNA in these EVs highlights the potential for ongoing immune modulation even in patients who have recovered from the acute phase of the disease.
 
Conclusion
The study’s findings underscore the complexity of the immune response in COVID-19 patients. Extracellular vesicles, particularly those carrying viral RNA, play a critical role in modulating the body’s inflammatory response. EVs with viral RNA were found to increase the production of certain immune-stimulating proteins while reducing others, suggesting that these particles influence the immune system in multiple ways. Additionally, miRNAs carried by EVs may further regulate inflammation, potentially contributing to the prolonged symptoms seen in long COVID patients.
 
By understanding the mechanisms by which EVs influence the immune system, researchers may be able to develop new therapies to manage the inflammatory response in COVID-19 patients. These findings also highlight the potential for using EVs as biomarkers to monitor the progression of the disease and guide treatment strategies. While more research is needed to fully understand the role of EVs in COVID-19, this study provides a crucial foundation for future investigations into the virus’s impact on the immune system.
 
The study findings were published in the peer-reviewed Journal of Leukocyte Biology.
https://academic.oup.com/jleukbio/advance-article/doi/10.1093/jleuko/qiae212/7778320
 
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