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    What Causes Long COVID? Micro Blood Clots May Be To Blame.

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    9 min read

    While Omicron is mild for many, some individuals develop long COVID brain fog, anxiety, depression, chronic fatigue, and other symptoms. New research suggests tiny blood clots in small capillary blood vessels may be the root cause of many long COVID symptoms. The blog below describes what these clots do to our bodies, brains, cognition, and emotions, and how Potomac Psychiatry’s Long COVID Brain Fog & Depression Program evaluates and treats this condition.

    In this blog, you will learn…

    Omicron May Be Mild, but the Long COVID Brain Fog Pandemic Persists

    My Dear Reader, as we begin a hopeful new year—one with masks mostly optional and vaccine cards hardly relevant—it feels like serious COVID illness is over. But is it? For many of us, the Omicron variants have brought mild symptoms and rapid recoveries. For some unlucky others, however, it continues to cause significant symptoms such as fatigue, depression, and brain fog. In a prior blog I outlined many potential causes of long COVID psychiatric symptoms, with some patients describing over 200 different symptoms which simply don’t abate. Today we will focus on one of these causes—tiny blood clots called microclots—and how we evaluate and treat disabling these clots in our Long COVID Brain Fog and Depression Treatment Program.

    The Role of Mitochondria in Creating Long COVID Symptoms

    Let’s begin with a brief tour of our 30 trillion cells in our body, and how they survive and thrive. Every single cell carries out one billion chemical reactions per second—and the mitochondria residing within these cells are the “power plants” that make them possible. Now, the average cell in our body hosts a few hundred mitochondria. However, many of our brain cells have millions of mitochondria inside of them. The reason is that, while our brains weigh only 3% of our body’s mass, they account for 20-25% of the body’s total energy production—after all, a staggering number of activities that need to be powered here: thinking, feeling, behavior, and even our consciousness.

    Each tiny mitochondria utilizes oxygen and nutrients from our bloodstream to produce, for their size, an energy equivalent of a lightning-bolt, powering the cells in which they reside. The tiny blood vessels that feed our brain cells—and those throughout our body—therefore need to carry lots of oxygen and nutrients to their mitochondria to drive power production. But what happens when oxygen and nutrients are cut off from the cells that need them? Simply put, such an event can quickly wreak havoc on our brains and bodies, starving them of the fuel they need to function at their best.

    You may be asking: What’s this have to do with long COVID? It turns out, quite a lot. You see, long COVID patients often display poor mitochondrial functioning… and that in turn can lead to a whole host of negative outcomes.

    How Does Long COVID Occur? A Step-By-Step Process

    According to new research, the mitochondrial powerplants in long COVID patients can become severely diminished, their lightning-bolt power reduced to a tiny spark. Within this context, symptoms of long COVID begin to make sense: if mitochondria power important functions throughout our bodies and brains, a diminished power supply would inevitably lead to less-than-optimal results. But what causes this energy starvation within our brain? Let’s explore the processes by which long COVID can develop.

    • COVID Causes Blood Vessel Inflammation: The blood vessels that feed brain cells their nutrients are lined with cells called endothelial cells. Think of these cells as analogous to the inner lining of the pipes in your home plumbing. The coronavirus, or even viral fragments themselves like spike proteins, can inflame these endothelial cells, which is called endothelialitis.
    • Inflammation Leads to Microclots: The inflammation from endothelialitis damages the inner lining of the blood vessels. These damaged areas subsequently attract platelet cells and other molecules that begin to form clots. Similar to the way mineral deposits inside your home plumbing can block the flow of water, these clots can block the blood flow in tiny microcapillary blood vessels—including the flow of oxygen and nutrients.
    • Microclots Starve Mitochondria: With clots narrowing the vessels, reducing the blood flow through them, less oxygen and nutrients are able to reach the cells and the mitochondria inside of them. This is the mechanism through which the mitochondria are starved and cannot produce enough energy, causing persistent fatigue throughout the body, which is known as “exercise intolerance” for many patients.
    • Starved Mitochondria Lead to Brain Fog, Depression, Fatigue, and More: In addition to producing fatigue, a brain that is starved of energy by microclots will produce numerous emotional, cognitive, and behavioral symptoms as well.

    Now that we understand this possible cause of long COVID, how do we diagnose and treat it?

    Could Testing for Microclots Reduce Symptoms of Long COVID?

    The science for the diagnosis and treatment of endothelial damage and microclots is still young and evolving. However, there are a number of laboratory test findings that can point the way. Tests such as IncellKINE, D Dimers, Factor VIII, α(2)-antiplasmin (α2AP), Serum Amyloid A, VEGF, and CRP can help determine whether microclots in a patient’s blood vessels may be perpetuating the symptoms of long COVID brain fog, depression, fatigue, anxiety, and numerous other symptoms. Let’s focus on IncellKINE, as it points the way toward effective treatments.

    IncellDx has developed the IncellKINE assay to test for molecules that promote inflammation. Using clinical research results combined with artificial intelligence, they provide treating physicians a written report with findings and treatment recommendations, and also offer a telehealth visit with one of their doctors for a live discussion of findings and recommendations. To learn more, please click here.

    A Deep Dive into a Possible Cause of Microclots

    Dr. Bruce Patterson is the clinician-scientist who has researched the causes of and treatments for long COVID, including endothelial damage, and developed the IncellKINE assay. I recently corresponded with Dr. Patterson, and was excited to learn that he is about to publish a paper about one of the causes of the endothelial damage and microclots, as well as a path forward to treat them:

    Dr. Patterson and his colleagues discovered that a type of white blood cell called a monocyte contains remnants of coronavirus spike protein (S1) in patients with long COVID. These altered white blood cells promote inflammation and live much longer than normal white cells. They circulate throughout the blood stream and then attach to a molecule called Fractalkine on the surface of the vessel endothelial cells. The Fractalkine then attracts other white cells and these all contribute to the inflammation of the blood vessel linings (causing the endothelialitis). This endothelialitis then activates blood platelets that release more inflammatory molecules, and this activation makes white blood cells and platelets stick together and also stick to the inflamed endothelium, causing the microclots that block the blood vessels. The blockages then starve the surrounding cells of the oxygen and nutrients needed to produce energy to power the cells.

    The study’s findings suggest that one way to interrupt the progression of the monocyte-endothelial-platelet activation is to use medications like maraviroc combined with pravastatin. This combination may restore normal immune system functioning in long COVID patients, and could therefore be a potential therapeutic option.

    Dr. Patterson concluded that this “endothelialitis signature” can be found using his IncellKINE 14-plex cytokine panel in other disease states as well. In 40,000 patients studied by using this test, this same pattern has been found in patients with long COVID, ME-CFS (chronic fatigue syndrome), Post-Lyme, and Fibromyalgia.

    How are Long COVID Microclots Treated to Improve Brain Fog, Depression, Anxiety and Fatigue?

    Dear Reader: These treatments should only be initiated while under the guidance and care of a medical professional, and should never form the basis of any self-care interventions.

    There are numerous treatment interventions being studied under large, rigorously designed, double blind, placebo controlled clinical trials. That said, patients suffering from long COVID understandably want answers today to end their prolonged emotional pain and cognitive dysfunction. Preliminary findings from multiple academic medical centers suggest that the following interventions may be helpful and in some cases curative. If an intervention doesn’t work in four to six weeks, patients can move on to the next one. Most are based on small case report studies and are awaiting confirmation in larger studies.

    What About Antidepressant Medication for Long COVID Depression?

    In our practice, the medication Trintellix has been quite helpful for some of my patients struggling with a post-COVID or post-vaccination depression. Trintellix not only boosts major neurotransmitters such as serotonin, dopamine, norepinephrine, histamine and acetylcholine, it also helps regulate the immune system by producing anti-inflammatory and immune system modulating effects. In human studies, it has been shown to reduce the overactivation of inflammatory molecules, quiets down overactive T cells, and reduces oxidative stress and free radicals that damage cells, proteins, and DNA.

    Feel Hopeful: Help is Available

    Omicron is milder that the Wuhan and Delta strains of the coronavirus, and thankfully, for many of us, our lives are returning to some semblance of normality. For those of you who are suffering from long COVID depression, anxiety, psychosis, PTSD, OCD, or other psychiatric conditions, please feel hopeful that the science to evaluate and treat your condition is rapidly advancing. If you’d like to learn more about how we evaluate and treat these conditions in our Long COVID Depression and Brain Fog Treatment Program, please contact us for a no-cost 15 minute consultation by emailing Dana Schwartz at Dana.Schwartz@PotomacPsychiatry.com.
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