In the early days of the pandemic, there was a perception across many populations that for the majority of people COVID-19 is relatively mild illness lasting for a weeks or so. However, in recent months we see increasing number of people who suffer with long lasting symptoms. NICE defines Long Covid as symptoms which last for more than 12 weeks and these symptoms are not explained by an alternative diagnosis. The long terms effects may include: fatigue, respiratory symptoms, neurological symptoms, “brain fog”, sleep disorders, fevers, gastrointestinal symptoms, anxiety.
Understanding the unique nature of Long Covid is essential for effective prevention and treatment. Despite what you may see in the press, we know a great deal about the causes of Long Covid and almost all can be reversed or treated.
First, a brief introduction to what happens to your body when you first contract Covid-19. For any virus to make you sick, that virus must attach to your cells, enter them, and cause damage within them. In the case of Covid-19, the gateway is ACE2, a vital enzyme that is essential for health and recovery from illness. When the Covid virus (called SARS-CoV-2) attaches to ACE2 in your cells, it damagesACE2. Virtually all complications of Covid-19 can be traced to an ACE2 deficiency. ACE2 deficiency can cause damage to the heart and blood vessels, which in turn can cause blood clots, actual loss of blood vessels, and impairment of circulation to vital organs like the brain. Loss of ACE2 also increases inflammation and scarring that can affect any organ in your body – including your lungs, nervous system, digestive tract, heart, kidneys, liver, and skin.
Once the virus destroys ACE2, the resulting inflammation impacts the mitochondria, tiny powerhouses inside your cells that generate 90% of the energy
you need to live. Even after a mild Covid infection, mitochondrial distress can continue for months. ACE2 deficiency and mitochondrial stress are the initial sources of nearly all the manifestations of Long Covid. The good news is that the reverse is also true: restoring ACE2 and rescuing mitochondrial function are the foundation for protecting yourself and healing from Long Covid.
It’s not uncommon, after someone has recovered from any virus, to experience some lingering symptoms, which are medically labelled “post-viral
syndromes.” But Long Covid is distinctly different from most other post-viral conditions, because it is more than just the persistence of symptoms that started with the initial infection. Covid enters your body as a respiratory infection, but it is essentially a circulatory disease, because the virus has a high affinity for the cells that line your blood vessels.
Once the virus attaches to the tissue that lines capillaries, veins, and arteries, it causes inflammation, and also causes microscopic blood clots that interfere with circulation, and therefore with the delivery of oxygen to your tissues. Every part of your body requires oxygen. This is why, even if Covid presented as an upper respiratory infection, similar to a cold, Long Covid can damage every part of your body – not just lungs, but also brain, heart, kidneys, liver, skin.
ACE2 depletion threatens more than circulation. A deficiency of intestinal ACE2 impairs the absorption of the essential amino acid tryptophan, causing a
cascade of other gut-based problems including bacterial and/or fungal overgrowth, and a depletion of serotonin and certain vitamins.
Most writing about Long Covid starts with definitions: what is Long Covid, how do you know you have it. In fact, there are many different types of long-term
problems that follow acute Covid-19. Some people get sick and don’t fully recover. Others appear to get well and then experience a relapse of their symptoms. For some people, a new set of symptoms emerges, either soon after acute Covid or sometime later, after another acute illness, usually an apparent viral infection. For many others, the problem is the appearance of a new disease within 6 to 12 months of having acute Covid-19. Diabetes, high blood pressure, immune problems and neurological or psychiatric disorders are twice as likely to develop during the year after Covid-19 than would be expected. There are still others for whom Covid-19 leads to an aggravation of an underlying condition that was previously mild and is now much more severe.
The symptoms associated with Long COVID are diverse and can manifest differently from person to person. Common symptoms reported by individuals with Long COVID include:
It’s important to note that these symptoms can persist for an extended period, significantly impacting an individual’s quality of life.
The exact cause of Long COVID is still not fully understood, and ongoing research aims to unravel its complexities. Several possible mechanisms have been proposed, including persistent viral presence, immune dysregulation, and post-viral inflammation. Additionally, the long-term impact on organ systems resulting from the initial infection may contribute to the development of persistent symptoms.
1.ENDOTHELITIS: this is inflammation of the cells that line your blood vessels, called the endothelium. This can actually lead to loss of the smallest blood vessels, called capillaries, and to stiffness of larger vessels like veins and arteries. Endothelitis may restrict blood flow and the delivery of oxygen to your
tissues. Restoring ACE2 in and of itself can alleviate both endothelitis and microthrombosis, but sometimes further measures are needed. Almost all these are measures you can implement yourself.
2. MICROTHROMBOSIS: Tiny blood clots that can clog capillaries. Microthrombosis aggravates endothelitis, and further restricts blood flow. The mechanism of microthrombosis in Long Covid is not the same as the formation of an ordinary blood clot. That’s why ordinary anti-clotting measures may not work.
3. MAST CELL ACTIVATION: Mast cells are primitive cells of the immune system, and are scattered throughout your tissues and organs. They do not circulate in your blood. Mast cells produce and secrete about 200 different chemicals, called mast cell mediators. The best known of these is histamine, which produces many symptoms of allergy. Mast cell mediators can cause constriction (narrowing) or dilation (widening) of blood vessels; they can also make blood vessels and membranes leaky, so that fluid escapes from them. Mast cell mediators may cause pain, swelling, redness, shortness of breath, diarrhea, high or low blood pressure. They contribute to migraine headaches, asthma and irritable bowel syndrome. In addition to causing symptoms on their own, mast cell mediators influence the function of more complex and evolved immune cells, like lymphocytes. Covid-19 can cause mast cell activation. In some people, once mast cells become activated, they do not “turn off” (i.e. they continue to release mediators that cause any of the above symptoms). Mast cell activation may contribute to microthrombosis and endothelitis. When patients for Long Covid have one of the problems listed above, or do not respond as expected or have unusual adverse reactions to treatments that should be helping them, mast cell activation is usually the cause. There are a number of approaches to control
of mast cell activation that can be self-administered. You can view an interview with Dr Leo Galland on Mast CellActivation in Long Covid
4. MONOCYTE POLARIZATION: Monocytes are a group of white blood cells involved in the immune response to Covid-19. Unlike mast cells, monocytes have a complex life cycle and change their functions as they move through it. Those functions are basically: attack, repair and patrol. (They attack anything that is perceived as a threat to the body; they repair the tissues that have been damaged; and they patrol to look for signs of danger.) Although most monocytes circulate in blood, some leave blood vessels to enter tissues, where they transform themselves into cells called macrophages. Polarization occurs when the normal life cycle is disrupted, shifting monocyte and macrophage function to create a disorganized immune response that favors chronic, unrelenting inflammation. You have probably read a lot about the chronic inflammation that creates Long Covid. Well, monocyte/ macrophage polarization plays a major role in maintaining that state. What’s important to know about this complicated phenomenon is that ACE2 helps to regulate the monocyte and macrophage life cycles to prevent polarization. Restoring ACE2 is the first step in reversing chronic inflammation. Because monocytes and macrophages need a lot of energy to function properly, mitochondria play an important role in maintaining their normal life cycles. So, the second step in correcting monocyte/macrophage polarization and tamping down chronic post-Covid inflammation is mitochondrial support.
5. AUTO-ANTIBODIES: Antibodies are proteins produced under the direction of specialized white blood cells called Blymphocytes. Their normal function is to bind to foreign molecules, like viral proteins, enabling their destruction and preventing them from doing damage. When you develop Covid19, your immune cells produce antibodies that recognize several foreign proteins made by the virus, like the spike protein. For many people with Covid-19, the antibodies produced not only attack the virus, they also attack cells of your own body. These are called auto-antibodies and the illness created is an autoimmune disease. The mechanisms involved in auto-antibody production are complex and there are many different kinds of auto-antibodies produced during the course of Covid-19, some of them unique to Covid. Most of the covid-induced autoantibodies only become active when there is inflammation and tissue damage. Decreasing inflammation is therefore the best protection against covid-induced autoimmunity.
6. T-CELL IMPAIRMENT: The generals of your immune system the cells that coordinate all aspects of your immune response—are called T-lymphocytes. There are many kinds (or subsets) of T-lymphocytes, and one type may be able to morph into another type. Here’s what’s important to know: SARS-CoV-2 can directly
invade T-lymphocytes and disable them. Impairment of Tlymphocytes makes it harder for you to eliminate the virus from your body, makes you more susceptible to repeat infection and also makes it more likely you will develop auto-antibodies. Restoration of T-cell function is an essential component of
healing from Long Covid, and is especially important for resolving the next strand of the web, Viral Persistence. T-cells, like monocytes, have an intense need for energy. Mitochondrial dysfunction impairs T-cell function and, in particular, shortchanges a critical type of T-cell called a T-effector memory (TEM) cell. TEM cell activity is essential for eradicating viral infections and for a robust response to vaccines. Some researchers have discussed re-activation of latent infections by other viruses as a result of Covid-19. Epstein Barr Virus (EBV, the cause of mononucleosis) lives sleeping in our Blymphocytes for most of our lives and is often awakened by acute Covid-19. TEM cells keep EBV and other latent viruses under control in their dormant states. A detailed description of
EBV in Long Covid is presented at the end of APPENDIX B. EBV reactivation in Long Covid is the direct result of TEM cell dysfunction. TEM cell activity is strongly influenced by the nature of bacteria that live in your gastrointestinal tract (the gut microbiome). Restoring mitochondrial function and creating a healthy gut microbiome are mainstays of my protocol for enhancing TEM cell function after Covid-19.
7. VIRAL PERSISTENCE: For many people with Long Covid, persistence of the virus, SARS-CoV-2, in their bodies, appears to be driving the ongoing inflammatory reaction. Persistence of SARS-CoV-2 has been demonstrated in different parts of the body for many months after the initial infection. Most scientists who study this believe the main location of viral persistence is in the gastrointestinal tract, which ties this strand to the next one, Gut Microbial Dysbiosis.
8. MICROBIAL DYSBIOSIS: Dysbiosis is a disturbance in the body’s microbiome, the population of 100 trillion microorganisms that cover every surface we have. About 99% of these organisms reside in the gastrointestinal tract, especially the large intestine. Dr Galland discussed the relationship between the gut
microbiome and Long Covid in an interview available online.
(a) People who develop Long Covid have lost important beneficial gut bacteria before they develop long COVID.
(b) These same people also show an overgrowth of potentially harmful gut bacteria.
(c) Butyrate, a chemical produced by many species of gut bacteria, is significantly reduced. Butyrate has potent healing powers throughout the body. Loss of butyrate has major implications for GI health and also for immune function and brain health. The reason for low butyrate appears to be loss of a keystone butyrate producer, a bacterial species called Faecalibacterium prausnitzii. (you cannot find this as a probiotic, so the name is not important).
(d) One of the dangerous bacteria that overgrows (Ruminococcus gnavus) produces a toxic metabolite called isoamylamine, which contributes to cognitive dysfunction and accelerates agerelated cognitive decline.
(e) All these changes in the gut microbiome may contribute to a phenomenon called “leaky gut”, in which the lining of the intestinal tract becomes porous, allowing gut-derived toxins to enter the body.
These findings make it likely that correcting the gut dysbiosis of Covid-19 will help recovery from Long Covid. The treatment
protocol for prevention and treatment of Long Covid
should pay special attention to establishing a healthy gut microbiome.
Given the complexity and diversity of Long COVID symptoms, a comprehensive approach is required for its management and treatment.
Conventional treatments offered to people with Long Covid are basically designed to reduce symptoms. Our goal is to address the causes of Long Covid that are described in the previous section, through self-care. Fortunately, most of these measures will also alleviate symptoms. The process starts with enhancing ACE2 activity and rescuing mitochondrial function.
Healthcare professionals often adopt a multidisciplinary approach that includes a combination of the following:
Symptomatic relief: Medications may be prescribed to alleviate specific symptoms such as pain, fatigue, or sleep disturbances.
Rehabilitation: Physical therapy, occupational therapy, and respiratory therapy can help individuals regain strength, improve function, and manage respiratory symptoms.
Mental health support: Access to mental health resources, counseling, and support groups are crucial for individuals experiencing anxiety, depression, or other psychological challenges associated with Long COVID.
Patient education: Providing accurate information and support to individuals with Long COVID is essential to help them understand the condition, manage their symptoms, and make informed decisions about their health.
Understanding and addressing Long COVID remains a significant area of research. Scientists are studying the long-term effects of the virus, potential risk factors, and the development of targeted interventions. International collaborations are underway to establish extended protocols to prevent and treat Long COVID and share findings to improve patient care.
Our Vision: We are paving the way to a world, where no life is lost or ruined by Coronavirus.