Originally published as a series of posts on www.x.com by Brain Inflammation Collaborative

Blood clots are not supposed to form inside blood vessels.

Yet, this type of clotting occurs during and after an active SARS-CoV-2 infection in the [brain], contributing to Long COVID symptoms like brain fog and neuroinflammation.

This paper (likely) discovered why...

\ The Discovery:

Scientists from UCSF discovered that the SARS-CoV-2 spike protein binds fibrinogen (and fibrin) enhancing clot formation.

This clotting is linked to the onset of:

• pulmonary embolisms (large [lung] clots during COVID-19)
• brain fog (smaller [brain] clots post-COVID-19)

The details are published here. https://nature.com/articles/s41586-024-07873-4#Sec47

\ Understanding Clot Formation: Fibrinogen is a soluble protein that circulates in the blood (at all times).

When an injury occurs the fibrinogen is modified into an insoluble fibrin polymer, aka a clot.

It's a temporary meshwork preventing a life-threatening loss of blood.

\ Clot Destruction:

Clots are destroyed when plasmin 'chops up' the fibrin into small fragments.

Plasmin also plays an important role in preventing clots from forming inside vessels, blocking:

• micro-clotting in the cerebral vasculature
• deep vein thrombosis
• pulmonary embolism
• stroke

​

\ Spike Prevents Clot Destruction (Fibrinolysis):

The spike protein was found to:

• promote clot formation and
• inhibit clot destruction

Clot destruction was inhibited b/c the spike binds the fibrin region that is cleaved by plasmin.

In other words - spike prevented plasmin from accessing fibrin to cut it and destroy the clot.

The latter might explain why clot-busting drugs do not work well in COVID-19 coagulopathies.

\ Neuroinflammation in Long COVID:

During COVID-19 the blood vessels in the brain become leaky losing their barrier (BBB) properties.

This causes fibrin to deposit in the brain vasculature to reduce the vessel's leakiness (aka a thrombus).

A monoclonal antibody was created to bind fibrin(ogen) at the same region spike binds.

The goal was to reverse spike binding to fibrin(ogen).

This monoclonal antibody reduced:

• excessive formation of fibrin deposits in the brain
• microglia activation in the mouse brain (aka neuroinflammation)

\ Monoclonal Fibrinogen-Binding Ab:

A humanized form of this monoclonal antibody was developed and is being tested in a phase 1 clinical trial.

Will this monoclonal antibody prevent/reverse the micro-clotting and microglia activation in the cerebral vasculature in humans?

If it does this might be a viable treatment for the long COVID effects on the brain like brain fog.

\ Inflammatory Consequences:

Last but not least, spike binding to fibrin(ogen) was also discovered to:

• suppresses natural killer (NK) cell function

NK cells are part of the innate immune system (don't require previous exposure or a vaccine to kill a SARS-CoV-2 infected cell during early stages of infection- usually in the lungs).

Blocking NK cell function might have contributed to the development of post-COVID pneumonia in many.

We envision a world where the neurophysiology of Long COVID is completely understood so it can be effectively treated.

Help us make our vision a reality by liking and sharing this content!

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