Etiology

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:

• Persistence of SARS CoV-2 S1 Protein in CD16+ Monocytes in Post-Acute Sequelae of COVID-19 (PASC) Up to 15 Months Post-Infection https://doi.org/10.1101/2021.06.25.449905
• (Youtube presentation) Immune-Based Prediction of Long Covid and Implications for ME/CFS https://youtu.be/O_XX9_IujeY

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:

• Immune-Based Prediction of COVID-19 Severity and Chronicity Decoded Using Machine Learning https://doi.org/10.3389/fimmu.2021.700782
• (Youtube discussion) Spike Proteins In Immune Cells - Dr. Bruce Patterson Discusses COVID Long Haul https://youtu.be/JwjJs5ZHKJI
• FLCCC I-RECOVER Protocol - https://covid19criticalcare.com/covid-19-protocols/i-recover-protocol/
• Cytodyn press release dated June 21, 2021 - https://www.globenewswire.com/news-release/2021/06/21/2250254/19782/en/CytoDyn-Inc-Announces-Positive-Preliminary-Results-of-Unblinded-Data-from-Long-Haulers-Trial-Showing-Greater-Improvement-in-Leronlimab-Group-over-Placebo-in-18-of-24-Symptoms.html

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:

• The SARS-CoV-2 spike protein subunit S1 induces COVID-19-like acute lung injury in Κ18-hACE2 transgenic mice and barrier dysfunction in human endothelial cells - https://doi.org/10.1152/ajplung.00223.2021