The dysregulated immune response is a key factor in severe COVID-19 cases, leading to complications such as acute respiratory distress syndrome (ARDS). A recent study conducted in Taiwan investigated the role of platelet-derived extracellular vesicles (EVs) and microRNAs (miRNAs) in promoting excessive neutrophil extracellular traps (NETs) formation in COVID-19 patients.
The study found that SARS-CoV-2’s spike protein directly activates platelets, causing an increase in the release of platelet-derived EVs (pEVs). These pEVs, when primed with spike protein, significantly enhance NETs formation. Toll-like receptor 8 (TLR8) and NADPH oxidase were identified as crucial components in this process. Additionally, two miRNAs, miR-21 and let-7b, which are abundant in platelets, were found to be upregulated in EVs derived from COVID-19 patients and associated with disease severity. These miRNAs interact with TLR8 to promote the production of reactive oxygen species (ROS) in neutrophils, leading to increased NETs formation.
Furthermore, the study demonstrated that EVs derived from COVID-19 patients and spike protein-primed pEVs carrying miR-21/let-7b induce the upregulation of proinflammatory cytokines in neutrophils. This occurs through the interaction with Toll-like receptor 7/8 (TLR7/8), ultimately activating NF-κB, a transcription factor involved in immune responses.
The findings of this study offer valuable insights into the molecular mechanisms underlying NETs formation in COVID-19. They suggest that targeting the regulation of proinflammatory cytokines and NETs formation, potentially through the use of TLR8 antagonists, NADPH oxidase inhibitors, or miR-21 inhibitors, could be promising therapeutic strategies for severe COVID-19 cases.
However, it is important to note that further research, including in vivo experiments, is needed to validate and expand upon these findings. Nonetheless, understanding the role of platelet-derived miRNAs and NETs formation in severe COVID-19 cases could potentially lead to improved treatment options and outcomes for patients.