Etiology: Difference between revisions

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'''References''':
'''References''':
* A Possible Role for Anti-idiotype Antibodies in SARS-CoV-2 Infection and Vaccination https://doi.org/10.1056/NEJMcibr2113694
* ''A Possible Role for Anti-idiotype Antibodies in SARS-CoV-2 Infection and Vaccination'' https://doi.org/10.1056/NEJMcibr2113694
 
==Blood clots and microclots==
 
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.
 
Another blood clotting theory comes from Etheresia Pretorius and her colleagues.  They studied long COVID patients and found that patients’ blood still contains anomalous microclots that are resistant to fibrinolysis (a normal body process that prevents naturally-occurring blood clots from growing and causing problems).
 
'''References''':
* ''Huynh, A., Kelton, J.G., Arnold, D.M. et al. Antibody epitopes in vaccine-induced immune thrombotic thrombocytopaenia. Nature 596, 565–569 (2021).'' https://doi.org/10.1038/s41586-021-03744-4
* ''Persistent clotting protein pathology in Long COVID/Post-Acute Sequelae of COVID-19 (PASC) is accompanied by increased levels of antiplasmin'' https://doi.org/10.1186/s12933-021-01359-7
* (Youtube) ''Interview with Dr. Resia Pretorius: LongCovid microclots (spike protein, apheresis + other topics)'' https://youtu.be/C8tzTmVwEpM

Revision as of 20:04, 3 January 2022

S1 spike protein

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

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 claims “positive preliminary results”.

References:

S1 spike protein toxicity

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.

References:

Full length spike protein toxicity

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 vaccines lead to vaccine injury.

References:

Auto-immunity

(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

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 auto-immunity against the ACE2 receptor. It may explain a small portion of all vaccine injuries.

References:

Blood clots and microclots

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.

Another blood clotting theory comes from Etheresia Pretorius and her colleagues. They studied long COVID patients and found that patients’ blood still contains anomalous microclots that are resistant to fibrinolysis (a normal body process that prevents naturally-occurring blood clots from growing and causing problems).

References:

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