What Causes LongCovid

What Causes LongCovid or Longhaulers Syndrome?

One theory is that Longhaulers are no longer infected with the Covid-19 virus — the virus is called SARS-CoV-2 — and their symptoms are caused by either damage to their organ systems or by immune system dysregulation. I disagree.

I think the virus is still found in Longhaulers. In the Patient-Led Longhaulers Survey [52], 45% of those who were tested, had a positive PCR test. Others have clear symptoms that their body is battling the Covid-19 virus, though with a negative test. If so many Longhaulers have the Covid-19 virus, it seems that the cause of the condition is that virus.

So I believe the hypothesis that the virus is still present in the bodies of Longhaulers, which is why they do not gradually recover, as we might expect if the virus were gone, and the body simply needed healing. But if the virus is still present, why doesn’t the immune system clear the virus? The hypothesis is that the virus hides in Immune Privileged Cells (IPCs), where the immune system can’t reach the virus. In addition, SARS-CoV-2 (the Covid virus) is particularly good at evading and even attacking the immune system. So once the virus becomes established in Immune Privileged Cells, the immune system cannot clear it on its own.

Which cells or sites in the body are “Immune Privileged”? One place is the anagen hair follicles, the hair follicles when new growth is occurring [78]. And that explains why the hair of Longhaulers sometimes falls out. The virus has infected those cells and is disrupting their normal function, causing the hair loss.

Another Immune Privileged site is the Central Nervous System (CNS) [See 77]. And that explains why Longhaulers often have symptoms from the CNS, like “brain fog” (i.e. difficulty concentrating or focusing), headache, difficulty sleeping, anxiety, memory problems, dizziness, confusion, and irritability. [See also the section below on the Autonomic Nervous System (ANS).]

The eyes are an immune privileged site. So are the nerves that provide the senses of smell and taste. And Longhaulers sometimes have symptoms from these IPCs as well: loss of the senses of taste and smell, blurry vision. The Survivor Corps Survey [51], reported eye symptoms, including: floaters or flashes of light in vision, blurry vision, dry eyes, and eye stye or infection. Then the Patient-Led Survey [52] also reported eye symptoms: eye burning, changes to the eye (including eye discharge and redness on the outside of the eye), sensitivity to light, blurry vision, and double vision.

All these symptoms from hair loss to brain fog to eye problems and loss of taste and small are explained by the virus infecting and disrupting Immune Privileged Cells. And the very definition of Longhaulers, that the symptoms continue long-term, is explained by this also. The immune system can’t clear the virus from Immune Privileged Cells (IPCs).

But then why do Longhaulers have regular Covid-19 symptoms as well, which are from places in the body outside of IPCs? And why do Longhaulers’ symptoms often show an episodic pattern of rising and falling? This occurs because the virus, from within Immune Privileged Cells, begins to multiply and spread throughout the body. Then, once it is outside of IPCs, the immune system can fight against the virus and clear it — though not in the CNS and other immune privileged sites. So the virus shows a pattern of multiplying and spreading, causing rising symptoms. Next, it is beaten back by the immune system into its hiding place in the IPCs, reducing certain symptoms for a while. But later the virus multiplies, and makes another foray out of the IPCs into the rest of the body, causing a repeating rise and fall in symptoms.

In the study titled “An Analysis of Self-reported Longcovid Symptoms on Twitter” [53], the most common symptoms were: “fatigue, shortness of breath, pain and brainfog/concentration difficulties.” But the study also found that “The most common course of symptoms was episodic.” Shortness of breath is explained by the repeated rise in viral load and repeated spread into the rest of the body, from the IPCs. The lungs are vulnerable to Covid-19, as we know from the usual course of the disease. When the virus spreads outside of IPCs, the lungs are likely to be re-infected. Fatigue is a result of the CNS being constantly infected, and also the damage to the rest of the body, which occurs in repeated cycles. Similar symptoms were reported in another social media-based study [54]. These cycles of viral multiplication and immune response weary the person, burden the immune system, and can cause excess inflammation.

But once the immune system learns to recognize the virus (by the adaptive arm, with T-cells and antibodies), how can the virus leave the Immune Privileged sites in the body? Wouldn’t the antibodies and T-cells destroy it immediately? No, for this virus is particularly good at evading the immune system, and it even has ways to directly attack the immune system. See the article: How Covid-19 Attacks your Immune System.

But why do some Longhaulers test positive for Covid-19, and others test negative? When the virus is hiding in IPCs, it is not accessible to testing swabs in the mouth and throat. But when the virus multiplies and spreads beyond the IPCs, then it is accessible to the testing; and as this spread happens episodically, some tests will be positive and some will be negative.

Dysautonomia

Is dysautonomia related to Covid-19 or LongCovid? “Dysautonomia or autonomic dysfunction is a condition in which the autonomic nervous system (ANS) does not work properly. This may affect the functioning of the heart, bladder, intestines, sweat glands, pupils, and blood vessels.” [Wikipedia]. Here are the symptoms of dysautonomia, listed by Wikipedia:
“Anhydrosis
Anxiety
Blurry or double vision
Bowel incontinence
Brain fog
Constipation
Dizziness
Difficulty swallowing
Exercise intolerance
Insomnia
Low blood pressure
Orthostatic hypotension
Syncope
Tachycardia
Tunnel vision
Urinary incontinence or urinary retention
Vertigo
Weakness”
The above list of symptoms of dysautonomia bears many similarities to a symptom list of LongCovid/Longhaulers Syndrome.

Perhaps inflammation, caused by Covid-19, results in a type of dysautonomia. If so, then steroids may be helpful.

However, the ANS is closely connected to the CNS. And SARS-CoV-2 does have the ability to infect neurons directly. “There is a growing body of reports indicating that COVID-19 patients, especially those in severe condition, exhibit neurological symptoms, thus supporting the possibility that SARS-CoV-2 could infect and damage neurons within the central nervous system in humans.” [79] Another study “provides evidence that SARS-CoV-2 can infect neural cells, likely contributing to neurological outcomes and possibly to neurodevelopmental disorders.” [80] Symptoms such as loss of taste and smell further support the conclusion that SARS-CoV-2 is a neurotropic virus, a virus that infects nerve cells. The virus has been found in CFS fluid and a large percentage of ordinary Covid-19 patients have neurological symptoms [80, 81, 82]. The virus has been shown to “affect diverse organs, including the central and peripheral nervous system [82].” And of course the peripheral nervous system includes the autonomic nervous system (ANS).

Thus, the close connection between the CNS and ANS means that spread from the CNS is very likely to affect the ANS strongly. Thus, the many neurological symptoms of LongCovid can be explained by the infection of the CNS with the consequent or concomitant infection of the ANS as well as by the repeated spread of the virus into the rest of the body.

More reading here:

* Original Hypothesis by Dr. William Petri (“Does coronavirus linger in the body?”)
* The Longhaulers Hidden Virus Hypothesis (updated)
* Immune Privileged Cells affected by Longhaulers Syndrome

How Does The Virus Enter IPCs?

There is a process whereby cells from the immune system move through the blood vessel walls into the place of infection (e.g. the lungs). This is called “extravasation”. See the following quote from Wikipedia: “Leukocyte extravasation (also commonly known as leukocyte adhesion cascade or diapedesis – the passage of cells through the intact vessel wall) is the movement of leukocytes out of the circulatory system and towards the site of tissue damage or infection.” [Wikipedia]

However, the blood vessel walls are also part of the Blood Brain Barrier (BBB). And the Immune Privileged Cells of the CNS are behind that barrier. “When BBB is ruptured, immune privilege is lost” in the CNS [76]. When the process of extravasation occurs in Covid-19, along with excessive inflammation and immune system dysregulation, I propose that this is what allows the virus through the BBB. Extravasation becomes excessive, allowing things through that would ordinarily not be permitted through, specifically the virus. And this is how Covid-19 becomes established in IPCs, causing LongCovid, or Longhaulers Syndrome.

So first you have a regular case of Covid-19, and the virus is not yet in the IPCs. Then the inflammation and immune system dysregulation allows the virus, by a disordered version of extravasation, to access those protected areas, and the virus becomes established in IPCs. And now the immune system can’t clear the virus, not even with adapted T-cells and antibodies.

Similarly, pneumonia in Covid-19 can also be caused by out-of-control extravasation, which allows fluids through the blood vessel walls. The lungs become burdened with excess fluid, making breathing difficult, which results in either pneumonia or ARDS.

That is the theory as to what causes LongCovid or Longhaulers Syndrome.

Author: Ronald L. Conte Jr.
[The author of this article is not a doctor or healthcare professional.]

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Endnotes:

The endnotes are incomplete because this article is an excerpt from a longer piece, not yet completed. When will it be completed? Ask God.

51. Lambert, N. J. & Survivor Corps., COVID-19 Long Hauler Symptoms Survey Report. Indiana University School of Medicine; 2020. Report Link (PDF)

52. Assaf, Gina, et al. “What Does COVID-19 Recovery Actually Look Like?”, Analysis of the Prolonged COVID-19 Symptoms Survey by Patient-Led Research Team; May 11th, 2020. PatientResearchCovid19.com; Report Link (PDF)

53. Singh, Shubh Mohan, and Chaitanya Reddy. “An Analysis of Self-reported Longcovid Symptoms on Twitter.” medRxiv (2020).

54. Banda, Juan M., et al. “Long-term patient-reported symptoms of COVID-19: an analysis of social media data.” medRxiv (2020).

…

76. Molina, Patricia E. “Neurobiology of the stress response: contribution of the sympathetic nervous system to the neuroimmune axis in traumatic injury.” Shock 24.1 (2005): 3-10.

77. Chavarría, Anahí, and Graciela Cárdenas. “Neuronal influence behind the central nervous system regulation of the immune cells.” Frontiers in integrative neuroscience 7 (2013): 64.
“The central nervous system (CNS) has a highly specialized immune-modulatory microenvironment, which has developed several mechanisms to protect itself from immune-mediated inflammation. This microenvironment is sustained by existing physiological and anatomical elements such as the blood-brain barrier (BBB) that limits peripheral immune cells and molecules entry; the afferent nerves of the autonomic nervous system with anti-inflammatory properties; and finally, the resident cells like astrocytes and neurons, which also contribute to the local immune privilege through the expression of anti-inflammatory suppressive factors and cell surface molecules (Carson et al., 2006).”

78. Pi, Long-Quan, et al. “Effects of calcitonin gene-related peptide on the immune privilege of human hair follicles.” Neuropeptides 47.1 (2013): 51-57.

79. Xu, Jiaxi, and Eric Lazartigues. “Expression of ACE2 in Human Neurons Supports the Neuro-Invasive Potential of COVID-19 Virus.” Cellular and Molecular Neurobiology (2020): 1-5.

80. Bullen, C. Korin, et al. “Infectability of human BrainSphere neurons suggests neurotropism of SARS-CoV-2.” ALTEX-Alternatives to animal experimentation (2020).

81. Song, Eric, et al. “Neuroinvasive potential of SARS-CoV-2 revealed in a human brain organoid model.” bioRxiv (2020).

82. Montalvan, V., et al. “Neurological manifestations of COVID-19 and other coronavirus infections: A systematic review.” Clinical Neurology and Neurosurgery 194 (2020): 105921.