Breakthrough in Long COVID: New Study Identifies Fibrin as Key Driver of Inflammation
- September 9, 2024
- Posted by: OptimizeIAS Team
- Category: DPN Topics
Breakthrough in Long COVID: New Study Identifies Fibrin as Key Driver of Inflammation
Sub :Sci
Sec: Health
Why in News
A recent study published in Nature on August 28, 2023, has identified fibrin as a key factor driving the inflammation and complications associated with COVID-19, rather than being a byproduct of the infection. This finding could change the way long COVID is understood and managed, offering a fresh perspective on potential treatments. The study, conducted using a mouse model, has opened up possibilities for new therapeutic strategies, especially using monoclonal antibodies.
Study Findings
Fibrinogen and Spike Protein Interaction: Using a mouse model, the researchers demonstrated that fibrinogen and fibrin bind with high affinity to the spike protein of the virus. This interaction plays a significant role in the inflammation seen in COVID-19 cases.
Clotting and Immune Response: The binding of fibrin with the spike protein alters the clot structure, making it more resistant to breakdown, which explains why clot-dissolving drugs are less effective in COVID-19 patients.
Inflammatory Mechanism: The study found that fibrin-spike protein interaction alters immune pathways, further exacerbating the inflammatory response.
Current Understanding of SARS-CoV-2 Pathogenesis
Vasculopathy and Inflammation: SARS-CoV-2 is widely known as a vasculopathic agent, meaning it damages blood vessels. Its severe complications, such as stroke, are linked to this damage.
Dominant Respiratory Symptoms: Most respiratory symptoms in COVID-19 are due to inflammation and clotting in the blood vessels of the lungs, not the airways.
Long COVID: Persistent inflammation and clotting mechanisms lead to long-term symptoms, termed as long COVID. These symptoms persist even after population immunity has reduced severe COVID-19 cases.
About SARS-CoV-2: Belongs to the coronavirus family (CoVs).
Causes a range of respiratory illnesses, from mild colds to severe diseases like SARS and MERS.
General Structure:
- Envelope: Composed of a lipid bilayer that protects viral components and facilitates cell entry.
- Spike Proteins (S): Crown-like spikes on the surface, key for binding to host cells.
- Nucleocapsid (N): Contains the viral RNA and aids in viral replication.
- Membrane Protein (M): Determines the shape of the virus envelope and plays a role in viral lifecycle.
Virus Particle Description:
- Identified as a betacoronavirus.
- Enveloped, spherical to pleomorphic particles, 80 to 160 nm in size.
- Contains a positive-sense single-stranded RNA genome.
Structural Proteins:
- Spike (S), Membrane (M), Envelope (E), Nucleocapsid (N) proteins form the structural basis of the virus.
- The S and M proteins extend across the membrane, essential for virus assembly.
- The N protein binds to RNA, forming the nucleocapsid, crucial for replication and influencing the host’s response.
Function of Spike Protein:
- Binds to the ACE2 receptor found in human respiratory, intestinal, and blood vessel cells.
- Its strong affinity to ACE2 enhances infection efficiency.
- Facilitates fusion with the host cell membrane, allowing viral RNA to enter and initiate infection.
Crown-Like Appearance: The polymerized spike proteins embedded in the viral envelope give SARS-CoV-2 its characteristic crown-like appearance.
Mutation Rate: As an RNA virus, SARS-CoV-2 has a higher mutation rate than DNA viruses.
This contributes to the emergence of new variants over time, making it a rapidly evolving pathogen.
Fibrin as a Key Player
Conventional View: Previously, it was thought that inflammation caused by SARS-CoV-2 damages the inner lining of blood vessels (endothelium), leading to fibrin deposition and blood clots.
New Perspective: The recent study reveals that fibrin actively binds to the spike protein of the virus, driving inflammation and complications in the lungs and brain, rather than just being a result of the infection.
Fibrin and Fibrinogen are key components involved in the blood clotting process. Fibrinogen is a soluble protein produced by the liver and circulates in the blood. When the body experiences injury or bleeding, fibrinogen is converted into fibrin through a series of chemical reactions triggered by the clotting process. Fibrin is an insoluble protein that forms a mesh-like structure, helping to trap blood cells and platelets to form a stable blood clot, preventing excessive bleeding. |
Monoclonal Antibody as a Potential Treatment
Therapeutic Strategy: The researchers tested a monoclonal antibody, 5B8, which targets the binding site of fibrinogen where the spike protein attaches. This antibody prevents the spike protein from binding to fibrin, reducing inflammation without affecting the normal function of fibrinogen.
About Monoclonal Antibodies:
Specificity: mAbs are highly specific, meaning they are designed to target only a particular antigen. This precision allows them to neutralize pathogens or block certain pathways involved in disease.
Production: Monoclonal antibodies are created by fusing a specific type of immune cell (B-cell) with a cancer cell to create a hybrid cell called a hybridoma. These hybridomas can be cultured to produce large quantities of a single type of antibody.
Therapeutic Uses:
- Cancer Treatment: mAbs can target cancer cells specifically, helping to deliver chemotherapy or radioactive substances directly to the tumor, reducing damage to healthy cells.
- Infectious Diseases: In diseases like COVID-19, mAbs can block the virus from binding to human cells, reducing its ability to spread in the body.
- Autoimmune Disorders: Monoclonal antibodies can inhibit inflammatory responses in diseases like rheumatoid arthritis and Crohn’s disease.
COVID-19 Treatment: During the pandemic, monoclonal antibodies were used to neutralize the spike protein of SARS-CoV-2, preventing the virus from entering human cells. Some antibodies also reduce inflammation and help in managing complications like long COVID.
Terminologies:
Persistent Thrombo-inflammation refers to a prolonged condition where both blood clotting (thrombosis) and inflammation occur simultaneously and continuously in the body. It is often seen in conditions like severe infections, autoimmune diseases, and chronic inflammatory states. This phenomenon can damage blood vessels and other tissues, leading to complications such as organ damage, strokes, or cardiovascular events.
ACE2 Receptor: A protein found on the surface of certain cells that acts as a gateway for SARS-CoV-2 to infect the host.
Positive-Sense RNA Virus: Viral RNA that can directly be translated into proteins by the host’s ribosomes.
Pleomorphic: Virus particles that can vary in shape and size.
Zoonotic Origin: SARS-CoV-2 is believed to have originated from animals, particularly bats.