French Researchers Uncover That Annexin-V Positive Extracellular Vesicles Could Be Promising Biomarkers Of Severe COVID-19 Disease
: The COVID-19 pandemic caused by the SARS-CoV-2 virus has wreaked havoc worldwide, leading to a significant number of severe cases requiring hospitalization in intensive care units (ICUs). Apart from respiratory distress, COVID-19 has been associated with various cardiovascular complications, including thromboembolic events as covered in numerous published case reports, studies and COVID-19 News
coverages. Understanding the underlying mechanisms behind these complications is crucial for effective management and treatment strategies.
Researchers from Amiens University Medical Center and Jules Verne University of Picardie in France conducted a study to assess the levels of extracellular vesicles (EVs) in COVID-19 patients and investigate their potential correlation with COVID-19-associated thromboembolic events. The study focused on endothelial and platelet membrane-derived EVs, specifically examining annexin-V positive EVs, which are known to play a role in apoptosis and blood coagulation regulation.
The study involved a cohort of 123 critically ill adults with acute respiratory distress syndrome associated with SARS-CoV-2 infection, ten adults with moderate SARS-CoV-2 infection, and 25 healthy volunteers. Annexin-V positive EV levels were measured using flow cytometry.
Of the critically ill patients, 34 (27.6%) experienced thromboembolic events, and 53 (43%) unfortunately succumbed to the disease. The study team found a significant increase in endothelial and platelet membrane-derived EVs in COVID-19 patients compared to healthy volunteers. Moreover, a slightly higher small/large ratio of platelet membrane-derived EVs was associated with thromboembolic events, indicating a potential link between EV characteristics and the occurrence of these events.
COVID-19 infection can cause severe respiratory distress and various cardiovascular complications, including thromboembolic events. The endothelium, which plays a critical role in regulating blood flow, coagulation, and inflammation, is significantly impacted by the virus. SARS-CoV-2 can bind to angiotensin-converting enzyme 2 (ACE-2) receptors expressed on endothelial cells, leading to endothelial dysfunction and inflammatory cell death.
Extracellular vesicles, including exosomes, microvesicles, and apoptotic bodies, have gained attention for their diverse functions and roles in intercellular communication. These vesicles carry lipids, nucleic acids, and proteins and can transfer their cargo to target cells, influencing various biological processes. In the context of COVID-19, EVs released by endothelial cells and platelets have been found to contribute to oxidative stress, endothelial activation, and coagulation dysregulation.
Annexin A5 (or annexin V) is a cellular protein in the annexin group. In flow cytometry, annexin V is commonly used to detect apoptotic cells by its ability to bind to phosphatidylserine, a marker of apoptosis when it is on the outer leaflet of the plasma membrane. Annexin A5 has been proposed to play a role in the inhibition of blood coagulation by competing for phosphatidylserine binding sites with prothrombin and also to inhibit the activity of phospholipase A1.
Interestingly, the study demonstrated s
ignificantly elevated levels of annexin-V positive EVs in severe COVID-19 cases compared to moderate infection and healthy controls. While the total EV levels did not correlate with thromboembolic events, the small/large ratio of platelet-derived EVs was slightly higher in patients who experienced such events.
This study finding suggests that EV characteristics, particularly in platelet-derived EVs, could serve as potential biomarkers for assessing the risk of thromboembolic complications in severe COVID-19 cases.
The investigation conducted by the French research team highlights the potential significance of annexin-V positive EVs as indicators of severe COVID-19 disease and associated thromboembolic events. Elevated levels of these EVs, especially in platelet-derived EVs, suggest their involvement in the procoagulant imbalance observed in severe infections. By analyzing EV characteristics, such as the small/large ratio, researchers may gain valuable insights into the underlying mechanisms of thromboembolic events in COVID-19 patients.
Further research is needed to explore the full potential of EVs as biomarkers and understand their specific roles in COVID-19 pathogenesis. Nevertheless, this study represents an important step towards unraveling the complexities of COVID-19-related complications and developing more effective strategies for managing severe cases.
The study findings were published in the peer reviewed journal: Frontiers in Medicine.
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