Nikhil Prasad Fact checked by:Thailand Medical News Jun 29, 2024 3 days, 17 hours, 51 minutes ago
COVID-19 News: Amid the chaos of the COVID-19 pandemic, scientists have been racing to understand how the virus wreaks havoc on the body. One of the major complications in severe COVID-19 cases is the development of blood clots and inflammation, leading to severe complications and even death. However, recent research has shed light on a potential savior - Protein C. This fascinating discovery covered in this
COVID-19 News report is based on a study by researchers from Universidade Estadual de Campinas-Brazil, Omaha VA Medical Center-USA and the University of Nebraska-USA which could pave the way for new treatments and better outcomes for COVID-19 patients.
Protein C Pretreatment Protects Endothelial Cells from SARS-CoV-2-Induced Activation
Panels comparing endothelial activation induced by SARS-CoV-2 and the cytoprotective effect of aPC. Left panel: The crucial role of endothelial cells in the pathogenesis of COVID-19 is related to the EC response to SARS-CoV-2 viral infection by detecting the adjacent infection and mounting a pro-inflammatory response to SARS-CoV-2 by stimulating circulating proteins. In addition, it is possible that even if direct infection in the ECs by SARS-CoV-2 does not occur, exposure to the virus is sufficient to promote transcriptional changes that lead to upregulation of pro-inflammatory and pro-coagulation genes and downregulation of cytoprotective signaling via Apc/PAR-1. Under stress conditions, serum aPC levels naturally rise in response to tissue damage; however, these levels may subsequently fall, allowing the already-known correlation of initially high serum aPC levels being associated with a worse prognosis in COVID-19. Right panel: The inactive PC might be stored in the EC (completing the PC reserve), and as soon as the cell is exposed to the virus, this protein promptly becomes activated and protects the vascular bed; consequently, its cytoprotective, anti-inflammatory, and anti-clotting signaling occurs more rapidly, thus actually protecting the cell from deleterious viral effects. PAR-1: Protease-activated receptor type 1; PC: Protein C; aPC: activated protein C; CCL2:C-C Motif Chemokine Ligand 2; ITGAM: Integrin Subunit Alpha M; VCAM1: vascular cell adhesion molecule 1; VWF: Von Willebrand factor.
Blood Clots and Inflammation in COVID-19
Severe COVID-19 can lead to significant problems with blood clotting and inflammation, primarily due to the damage the virus causes to endothelial cells, which line the inside of our blood vessels. When these cells are damaged, it can trigger a cascade of events that result in the formation of blood clots and widespread inflammation. This condition is known as coagulopathy and is a major cause of complications in COVID-19 patients.
The Role of Endothelial Cells
Endothelial cells are crucial for maintaining the health of our blood vessels. They help regulate blood flow and prevent the formation of clots. In healthy individuals, these cells work efficiently to keep the blood flowing smoothly. However, wh
en the endothelial cells are damaged by the SARS-CoV-2 virus, they can no longer perform their protective functions effectively. This damage exposes the underlying tissues to the blood, leading to the activation of clotting factors and the formation of blood clots.
Enter Protein C: The Body's Natural Protector
Protein C is a protein that plays a key role in controlling blood clotting. When activated, it can help prevent excessive clotting and inflammation. The body naturally produces Protein C, but in severe COVID-19 cases, its levels can become depleted, making it harder for the body to control blood clotting and inflammation.
What is Protein C
Protein C, also known as autoprothrombin IIA and blood coagulation factor XIV, is an inactive enzyme (zymogen) that, when activated, plays a crucial role in regulating anticoagulation, inflammation, and cell death, and in maintaining blood vessel wall permeability. Activated Protein C (APC) inactivates proteins Factor Va and Factor VIIIa, functioning as a serine protease. Encoded by the PROC gene on chromosome 2, Protein C is a vitamin K-dependent glycoprotein that circulates in blood plasma as a two-chain polypeptide. Its activation, enhanced by thrombomodulin and endothelial protein C receptors (EPCRs), primarily occurs near endothelial cells, influencing these cells and leukocytes. Deficiencies or resistance to APC lead to a higher risk of thrombosis. The recombinant form of APC, Drotrecogin alfa-activated (Xigris), was marketed for severe sepsis but was withdrawn in 2011 due to increased mortality and bleeding risks.
The Study: Investigating Protein C's Protective Effects
A group of researchers conducted a study to investigate whether pre-treating endothelial cells with Protein C could protect them from the damaging effects of SARS-CoV-2. The study involved treating human umbilical vein endothelial cells (HUVECs) with inactive Protein C before exposing them to the virus or serum from severe COVID-19 patients.
Key Findings: Protein C Shows Promise
The results of the study were promising. The researchers found that pre-treatment with Protein C significantly reduced the expression of genes involved in inflammation and blood clotting in cells exposed to the virus. Specifically, genes like CCL2, IL6, and SERPINE1, which are associated with inflammation and clotting, showed decreased expression. This suggests that Protein C can help protect endothelial cells from the damaging effects of the virus.
Implications for Treatment: A New Hope
These findings have important implications for the treatment of severe COVID-19. By boosting the levels of Protein C in patients, it may be possible to reduce the risk of blood clots and inflammation, leading to better outcomes. While more research is needed to fully understand how best to use Protein C in clinical settings, this study provides a hopeful glimpse into a potential new treatment strategy.
Real-World Impact: Better Outcomes for COVID-19 Patients
The potential benefits of using Protein C in COVID-19 treatment are significant. By protecting endothelial cells and preventing the formation of blood clots, Protein C could help reduce the severity of complications in COVID-19 patients. This could translate to fewer ICU admissions, shorter hospital stays, and, ultimately, more lives saved.
Looking Ahead: The Path to New Treatments
Moving forward, it will be crucial to conduct further studies to confirm these findings and determine the best ways to use Protein C in clinical practice. Researchers will need to explore the optimal dosing, timing, and administration methods to maximize the benefits of Protein C for COVID-19 patients. With continued effort and collaboration, the scientific community can turn these promising results into real-world solutions that improve patient outcomes and save lives.
Conclusion: A Step Forward in the Fight Against COVID-19
The discovery of Protein C's protective effects against COVID-19-induced blood clotting and inflammation is a major step forward in the fight against the pandemic. While there is still much to learn, this research offers a glimmer of hope and underscores the importance of continued scientific investigation. As we continue to uncover the mysteries of COVID-19, discoveries like this bring us closer to effective treatments and a brighter future.
The study findings were published in the peer reviewed journal: Viruses.
https://www.mdpi.com/1999-4915/16/7/1049
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