Etiology

From Long Haul Wiki
Jump to navigation Jump to search

There are many different theories regarding post vaccination syndrome (the most debilitating and common form of COVID vaccine injury) and long COVID. While most theories could explain both conditions, some theories only apply to long COVID.

It is entirely possible that none of the current theories are correct. So, we should keep an open mind and be willing to change our mindset when the facts change.

Post vaccination syndrome (vaccine injury)[edit]

S1 spike protein[edit]

S1 spike found 15 months post COVID infection
S1 spike found post vaccination

Both long COVID and vaccine injury seem to be very similar conditions due to similarities in symptoms and how patients respond to the same treatments. There are various theories as to why ‘long haul’ occurs in both groups. One theory is that the S1 subunit of the spike protein is the root cause. Bruce Patterson, a former Stanford researcher, led a team that found persistent S1 spike protein in non-classical monocyte (CD14+ CD16+) cells up to 15 months after initial infection.

There are two possibilities as to why spike proteins persist in non-classical monocytes.

  • The monocytes are immortal or near-immortal. They do not die in 7 days like typical non-classical monocytes.
  • The S1 spike protein is like a ‘bone’ that the body cannot break down. It is passed on from monocyte to monocyte.

References:

S1 spike protein causing vascular inflammation[edit]

According to this theory, persistent S1 spike protein leads to non-classical monocytes provoking vascular inflammation. That vascular inflammation is somehow able to drive the diverse range of symptoms that long haulers experience.

  • Drugs like statins interrupt the fractalkine/CX3CR1 pathway, disrupting nonclassical monocytes from sticking to the walls of blood vessels and engaging in pro-inflammatory behavior.
  • Various drugs may affect the survival of non-classical monocytes or have been shown to affect monocyte repolarization in vitro: statins, melatonin, omega-3 fatty acids, vitamin C, vitamin D.

Bruce Patterson’s company, IncellDX, produces a test kit that measures various inflammatory markers. Various cytokine levels are elevated in long haul patients.

  • CCR5 antagonists like maraviroc and the experimental drug leronlimab may counteract the elevated levels of CCL4/RANTES found in many (but not all) long haulers. Cytodyn’s study of leronlimab on long haul did not reach statistical significance. Nonetheless, the company states that the trial was not designed to reach statistical significance (the sample size was 56 patients) and that the early-stage trial delivered “positive preliminary results”.

References:

S1 spike protein persistence in exosomes[edit]

Whereas Bruce Patterson found evidence of persistence in non-classical monocytes, Bansal et al believe that spike protein is persistent in exosomes at 4 months after the second round of vaccination. An analysis of the study by Michael Palmer and Sucharit Bhakdi argues that the surprisingly long persistence " raises the prospect of sustained inflammation within and damage to organs which express the spike protein".

References:

S1 spike protein toxicity[edit]

An experiment on a mouse model (K18-hACE2 transgenic mice) demonstrated that an injection of spike protein leads to acute lung injury.

The researchers in the study also examined whether the splitting of the spike protein is relevant. The spike protein consists of S1 and S2 subunits joined at the furin cleavage site. The researchers used a protease inhibitor cocktail to prevent the splitting of the spike protein (into S1 and S2) at the furin cleavage site. Unsplit spike protein did not lead to damage while split spike protein led to damage, presumably due to how S1 spike protein affects the ACE2 pathway.

This study may not necessarily generalize to vaccine injury because it was focused on an acute COVID context. Because there are differences between acute COVID and vaccine injury, the mechanisms for each may be different. Whereas acute COVID patients generally have low oxygen levels in their blood (presumably due to lung damage), vaccine injured patients generally have normal oxygen levels.

A Korean research team lead by Junyoung Oh tested mice by injected S1 spike protein into their hippocampus. While the S1 protein did not directly induce hippocampal cell death in vitro, it exerted neurotoxicity via glial cell activation, partially through interleukin-1β induction.

References:

Full length spike protein toxicity[edit]

Some believe that full-length spike protein may be the cause of vaccine injury, as full-length spike protein has been shown to impair DNA repair in a laboratory setting. One of the problems with this theory is that it predicts that partial-length spike vaccines like Pfizer would have far fewer side effects than full-length spike vaccines. In practice, both types of vaccines lead to vaccine injury. The vaccine differenes page contains some additional information on spike protein differences between COVID vaccines.

References:

Auto-immunity[edit]

(Auto-immunity is when the immune system engages in ‘friendly fire’ and attacks host tissues instead of foreign invaders.)

Long haulers tend to have elevated auto-antibody levels when their blood is tested by Cell-Trend, a German lab. This has some similarity to auto-antibodies found in the blood of acute COVID and long COVID patients:

  • A study by Gerd Wallukat and his team examined the antibodies of 31 recovered COVID-19 patients. All had between 2 and 7 different auto-antibodies of the GPCR-fAAB type (g-protein coupled receptor functionally active auto-antibodies). In healthy controls, such auto-antibodies are only found in a small percentage of people.
  • Yale researchers looked for auto-antibodies against a library of 2,770 human extracellular proteins. They found correlations between the progression of disease and auto-antibody levels, suggesting that a COVID-19 infection causes auto-antibody production. They also found that “mouse surrogates of these autoantibodies increase disease severity in a mouse model of SARS-CoV-2 infection”.

To treat long haulers, many doctors are repurposing treatments normally used for auto-immune conditions: corticosteroids, immune-suppressing drugs used for rheumatoid arthritis, IVIG, apheresis, etc.

References:

Antibodies against antibodies[edit]

It has been observed that animals generate antibodies against antibodies produced by their own immune system. (This may be a form of down-regulation.) Researchers refer to them as “anti-idiotype antibodies”. If the immune system is exposed to spike protein, resulting anti-idiotype antibodies could bind to the ACE2 receptor. A paper on the topic states:

This aspect of regulation of immune-cell responses [antibodies against antibodies] was postulated by Plotz in 1983 as a possible cause of autoimmunity arising after viral infection5 and has since been supported experimentally by direct transfer of anti-idiotype antibodies.

This theory explains why there may be auto-immunity against the ACE2 receptor (but does not explain why other auto-antibodies are common in long haulers). It may explain a small portion of all vaccine injuries.

References:

Blood clots[edit]

The adenovirus vector vaccines (Johnson and Johnson, AstraZeneca) have been associated with a rare blood clotting disorder called vaccine-induced immune thrombotic thrombocytopaenia (VITT). One paper (Huynh et al.) describes how such patients have antibodies against platelet factor 4 (PF-4), which is the cause of their VITT.

References:

Microclots[edit]

Another blood clotting theory comes from Etheresia Pretorius and her colleagues. They studied long COVID patients and found that blood samples contain anomalous microclots that are resistant to fibrinolysis (a normal body process that prevents naturally-occurring blood clots from growing and causing problems). Clinical application of their theory should provide evidence for or against the theory:

  • A pre-print from Resia Pretorius' team discusses the result of a multi-drug anti-clotting intervention. Strangely, the pre-print has very few details on patient outcomes such as which symptoms resolved and the degree of improvement. Nonetheless, the abstract claims: “Each of the 24 treated cases reported that their main symptoms were resolved and fatigue as the main symptom was relieved, and this was also reflected in a decrease of both the fibrin amyloid microclots and platelet pathology scores.”
  • A follow-up pre-print from Pretorius' team provides additional details on microclots in long COVID patients before treatment. While the pre-print claims that their testing is "simple and cost-effective", the paper only presents data on 30 of the 80 patients whose blood samples were analyzed.
  • Long COVID patients are currently being treated with HELP apheresis in Germany. There are some anecdotal patient outcomes being reported in the Facebook group "Help Apheresis for Long Covid and Post Viral Syndromes". A Youtube interview with Resia Pretorius also contains some comments on the effectiveness of apheresis, suggesting that the treatment does not lead to instant results.

It is currently unclear if post vaccination patients also have microclots like long COVID patients. An article in Science magazine states:

The cause of the very rare but severe clotting after the AstraZeneca and Johnson & Johnson vaccines remains unknown, but Pretorius suspects all COVID-19 vaccines might also sometimes trigger subtler clotting issues. She says she has preliminary evidence that vaccination can lead to microclots, although in most cases they go unnoticed and quickly disappear—an effect she and a colleague saw in their own blood and that of eight other healthy volunteers, which they sampled after their vaccinations.

References:

  • (Youtube) Interview with Dr. Resia Pretorius: LongCovid microclots (spike protein, apheresis + other topics) https://youtu.be/C8tzTmVwEpM
  • Combined triple treatment of fibrin amyloid microclots and platelet pathology in individuals with Long COVID/ Post-Acute Sequelae of COVID-19 (PASC) can resolve their persistent symptoms https://doi.org/10.21203/rs.3.rs-1205453/v1
  • Prevalence of symptoms, comorbidities, fibrin amyloid microclots and platelet pathology in individuals with Long COVID/ Post-Acute Sequelae of COVID-19 (PASC) https://doi.org/10.21203/rs.3.rs-1205453/v2

Mast cell activation syndrome (MCAS)[edit]

MCAS resembles mastocytosis, a rare disease caused by too many mast cells. People with MCAS have a normal number of mast cells that are overly active and cause dysfunction.

Some MCAS specialists believe that long COVID is rooted in MCAS. Other MCAS specialists note that MCAS symptoms are prevalent in long COVID patients.

References:

Multiple persistent infections[edit]

Vaccine injury has similarities to other debilitating, poorly-understood illnesses:

  • Breast implant illness. Many but not all people with breast implants report significant reversal in their health problems after removing their breast implants. The scientific literature refers to this illness as siliconosis, silicone implant incompatibility syndrome, and ASIA (autoimmune/Inflammatory syndrome induced by adjuvants).
  • Chronic Lyme (“PTLDS”) and Lyme+.
  • ME/CFS.
  • Gulf War syndrome.
  • HPV vaccine injury.
  • Post viral syndromes from SARS1, MERS, Ebola, etc.
  • Long COVID / PASC.

All these illnesses share common features:

  • Overlapping symptoms, e.g. POTS, internal vibrations, derealization, etc.
  • Patients vary widely in the symptoms that they do and don’t have.

The similarities could be explained by multiple persistent infections working together in weakening the immune system. When the immune system is overburdened, debilitating health problems surface. This overburdening could be triggered by stress (e.g. divorce), inorganic burdens like silicone implants, and organic sources such as new infections and S1 spike protein. More information on scientific evidence and treatment outcomes can be found on the multiple persistent infection page.

References:

ME/CFS[edit]

Craniocervical instability (CCI), Chiari, mechanical issues, etc.[edit]

The theory is that physical injury is responsible for ME/CFS (and possibly long COVID). Such injuries can be triggered by a virus, an impact trauma, or other events.

Jen Brea and Jeff Wood are ME/CFS patients who experienced a ME/CFS following a series of surgeries. Jen Brea has since unfortunately developed new chronic health problems following long COVID, as discussed in a #MEAction news item. There has also been one case of disabling results following surgery (occipitocervical fusion and posterior fossa decompression): https://www.jkrowbory.co.uk/2020/01/post-surgery-update-on-jenny/

Some patients with mechanical issues seem to see some symptom relief from neck braces, avoiding changes in barometric pressure from flying, living at lower altitudes, etc.

Resources:

Long COVID / PASC (Post-acute Sequelae of COVID-19)[edit]

Viral reservoir[edit]

Some portion of long COVID sufferers may actually have a reservoir of actively replicating virus, e.g. in the digestive system.

References:

  • Persistence of intestinal SARS-CoV-2 infection in patients with COVID-19 leads to re-admission after pneumonia resolved https://doi.org/10.1016/j.ijid.2020.04.063
  • SARS-CoV-2 infection and persistence throughout the human body and brain https://doi.org/10.21203/rs.3.rs-1139035/v1 - This pre-print argues that SARS-CoV-2 can persist throughout the body and in the brain.
  • COVID-19 Endothelial Dysfunction Can Cause Erectile Dysfunction: Histopathological, Immunohistochemical, and Ultrastructural Study of the Human Penis https://doi.org/10.5534/wjmh.210055 - viral persistence in the penis
  • Persistence of residual SARS-CoV-2 viral antigen and RNA in tissues of patients with long COVID-19 https://doi.org/10.21203/rs.3.rs-1379777/v1 - Persistence in appendix and breast tissue
  • SARS-CoV-2 infection and persistence throughout the human body and brain https://doi.org/10.21203/rs.3.rs-1139035/v1 - An autopsy study found evidence of virus persisting in acute COVID patients, though it is unclear if these findings would generalize to long COVID patients. 89% of the patients died from COVID while 11% died with COVID. 13.6% of the patients had 'chronic immunosuppression' as a comorbidity, which could explain why virus was found for "up to 230 days following symptom onset".

Gut microbiome reservoir[edit]

Some papers suggest that SARS-CoV-2 may actively replicate in gut bacteria, potentially explaining why viral RNA persists in fecal matter for several months in some patients.

References:

  • Gastrointestinal symptoms and fecal shedding of SARS-CoV-2 RNA suggest prolonged gastrointestinal infection https://doi.org/10.1016/j.medj.2022.04.001 - 4% of patients with COVID-19 shed fecal viral RNA 10 months after diagnosis.
  • Could SARS-CoV-2 Have Bacteriophage Behavior or Induce the Activity of Other Bacteriophages? https://doi.org/10.3390/vaccines10050708 - This study suggests that SARS-CoV-2 may have bacteriophage behavior (or bacteriophage-inducing behaviour) and that it may actually replicate in gut bacteria.

SARS-CoV-2 has potential 'superantigenic' mechanisms[edit]

Superantigens are potent antigens that can send the immune system into overdrive. SARS-CoV-2 may be acting as a superantigen that leads to the depletion of naive T and B-cells in individuals with Long COVID. Superantigens are implicated in the development of autoimmune diseases and could explain why autoimmunity is so prevalent in long haulers.

Hamdy and Leonardi suggest that vaccination is a solution to superantigens as vaccination would reduce the dose of superantigen that a patient receives. They use MIS-C as an example and make no mention of MIS-V, which is MIS (multisystem inflammatory syndrome) caused by vaccination.

References:

Damage from acute COVID[edit]

A COVID-19 case may have different mechanisms that may be responsible for long-term health consequences:

  • The SARS-CoV-2 virus infects a wide range of human cells.
  • The cytokine storm syndrome may be responsible for long-term damage. This may also result in functional exhaustion and decreased numbers of T lymphocytes and natural killer cells.
  • SARS-CoV-2 may drive multi-organ injury via stimulation of clotting cascades and related thromboinflammation, dysregulation of the renin–angiotensin–aldosterone system, and endothelial cell damage.
  • Post ICU syndrome

References:

Damage to the olfactory system (sense of smell)[edit]

Observational studies suggest that damage to the olfactory system is strongly associated with COVID infections. Lasting effects on the sense of smell may be related to the initial COVID infection.