One Long Covid Mechanism to Rule Them All?
Are microclots the Primary Event that causes Long Covid?
Diving into the Covid and Long Covid scientific literature at first feels like dropping into the middle of the most chaotic scene you can image - the floor of the New York Stock Exchange or a big box store on Black Friday or a battle in front of the gates of Mordor.
There are papers about everything from the effects of Covid on anatomy to measuring various symptoms in various populations to molecular level studies and data.
You see it all: inflammation, fatigue, cardiac disruptions (like POTS), post-exertion malaise (PEM), microclotting, lactate imbalances.
It literally makes your head spin as you try to make sense of all these things while asking the ONE critical question:
What is actually making people with Long Covid sick?
In my last post, I put together a “Catalogue of Long Covid Symptoms” that I planned to use as a starting point. The plan was to link each symptom with the biological pathways and molecular mechanisms/targets that caused each symptom, in an attempt develop a framework for how to treat Long Covid.
As with most plans, mine didn’t survive first contact with reality.
Here’s why: when you dive into the scientific literature at the molecular level, you begin to see that all of the molecular pathways, pathologies, and symptoms are interrelated and connected. Immune response causes endothelial cell damage. Endothelial cell damage causes microclots. Microclots cause inflammation and additional immune response. All of them together lead to phenotype level symptoms like fatigue, cognitive impairment, POTS, & PEM.
In Long Covid, we can’t look at anything in isolation because everything is connected.
But what we can do is separate the Primary Events that are caused directly by the Covid virus from Secondary Effects that result downstream.
Fortunately, a couple of very smart, capable, and unbiased clinician-researchers, Dr. Etheresia Pretorius & Dr. Douglas Kell, have taken that approach to Long Covid pathophysiology and proposed what I think of as the “Unified Hypothesis” for the Primary Events and Secondary Effects in Long Covid. They have published two review articles (Review #1 and Review #2) outlining this hypothesis and showing how ALL of the data from Covid and Long Covid fit into & are consistent with the hypothesis.
The simple statement of the hypothesis is this:
Abnormal, non-natural microclots, themselves caused by the protein(s) from the Covid virus or viral fragments, are the Primary Event that causes Long Covid.
All other molecular events, pathophysiology, and symptoms are Secondary Effects that occur downstream of the abnormal microclots.
The key to this hypothesis is the understanding that the microclots that form are ABNORMAL and NON-NATURAL. In the absence of being exposed to Covid protein(s), the body does NOT make these types of microclots.
And because these microclots are abnormal and non-natural, the normal systems of the body DO NOT break down these clots. At least not readily or rapidly.
So these abnormal microclots stick around in the body and cause all kinds of Secondary Effects: inflammation, immune response, Mast Cell activation, autoantibody production, low oxygen in the muscles and brain (leading to Fatigue, Brain Fog, Mitochondrial disruption), and potentially pain and tissue dysfunction from the microclots themselves.
In this “Unified Hypothesis” for Long Covid, the microclotting is the one mechanism that rules (causes) all the others (to continue the LOTR analogy).
When confronted with a hypothesis like this, I immediately always ask two strategic-level questions:
Is it really true?/How can we verify it?
How can we use it to help treat people?
Answering the “Is it true?” Question is a matter of critically reading the scientific literature and “stress-testing” the hypothesis with every piece of data available. That is going to be the subject of a lot of my posts for the foreseeable future. You can immediately start rattling off questions to test the hypothesis and verify it:
How do Covid proteins make the abnormal microclots form?
How do the microclots cause inflammation?
How do the microclots affect the immune system (good and bad)?
Can microclots form in the brain? If so, what effects do they have?
And on and on…
Answering the “How can we use it to help treat people?” requires a little more information, particularly on the molecular level. The abnormal nature of the microclots is the key to this. My thoughts and answers on that will be coming soon as well.
What do you think?
Can abnormal microclots be the Primary Event that causes all the other Long Covid Secondary Effects and symptoms?
Leave me a comment below and let me know what you think.
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