Notes on Omicron

Paradoxical Immune reactions

Remember, I have an Index article with the vast majority of my articles, you can use the search function in your browser and delve deeper into anything that pops your curiosity.

Most of my readers are used to complicated but broken down topics, even if takes more than one reading for the normal Joe, most of the time it is somewhat broken down to help anyone understand a topic. Structured writing. This time, it ain’t it.

You can interpret this as a stream of consciousness and my thoughts on Omicron. Given the number of hours researching SARS-CoV-2 from a bird’s eye perspective and going down many lines of inquiry while plagued with a large amount of confounder, given my analytical framework, I can distill signals in the noise, data in chaos. After a few months of the Omicron strain (I prefer calling it a strain, deal with it) displacing SARS-CoV-2 Delta, even taking into account the previous variables, one thing remained consistently across the board.

I prioritize specific research points with a simple decision-making process. “What will lead to helping the largest amount of people ?” and “Is there enough published research around for me to find some answers ?”. Given that Omicron wasn’t killing most people, and data was somewhat lacking, it went to the backburner.

If you go back into specific articles you will find my description of Omicron being “The reverse immune response previous SARS-CoV-2 variants”. So months ago that is exactly the perspective I chose to research, how could the reverse immune response lead to poorer health outcomes long-term (months).

A point I will skip, because I have raised it multiple times, regardless of vaccination status, Omicron has a significant and strong Th17 response, because it bypasses most of our antibodies, and we rely on our T-Cell response to protect us, antibody response is a secondary in this regard. So why isn’t “everybody fucked up” and “why an increasing number of infected people experience a cascade of secondary infections ?”. Sometimes it just takes time and the correct circumstances for you to change your perspective.

The intricacies of T-Cell exhaustion

Throughout the last two years, one specific protein always kept popping up, at odd places in many papers, unbeknownst to me, I already had a piece of this particular puzzle. TIM-3 is the protein’s name. TIM-3 is a receptor in T-cells that has a potent immunosuppressive role, as a receptor it needs “something” to initiate its effects, often referred to as ligands.

Upregulation of TIM-3 is directly responsible for the depletion and dysfunction of Natural Killer cells in SARS-CoV-2 cases, with findings being corroborated time, and time again. TIM-3 is also responsible for the long-term immune dysfunction observed in survivors of severe infection.

If the virus NTD, being a mimic of human Galectin-3 plays a significant role in many outcomes, it changes the fate of many cells, it literally “bridges” the gaps in all distinct and odd immune responses, perhaps Gal-3 sister would potentially play a role too. Incidentally, Gal-3 sister is the TIM-3 ligand. Galectin-9, unlike its chimeric brother, Gal-9 doesn’t interact with all sorts of proteins, but it has very important roles.

While the TIM-3-Gal-9 axis is a common trait in regards to how aggressive each strain is (Wuhan>Delta-Omicron), this axis is the predominant response in Omicron lineages. Depending on where Gal-9 finds itself, it can enhance SARS-CoV-2 infection, and the inflammatory response is what you would suspect, IL-6, IL-8, IL-17, EIF2, and TNFα signaling pathways. A comprehensive analysis of the systemic immune response of Omicron also showed it has a strong immunosuppressive response.

So what TIM-3-Gal-9 interaction can affect, besides the broad description of “immunosuppression”, and does it fit any of our avenues of inquiry ? Well, for starts this interaction directly affects primary and memory responses to viral infection in regards to CD8, affecting viral clearance. Soluble Gal-9 is a novel marker for the progression of atherosclerosis, and soluble Gal-9 is a certainty here, which is a problem for people already suffering from the disease or with some level of heart damage.

Gal-9 on its own can induce the reactivation of HIV, with TIM3/Gal-9 interacting with CD8 cells it can affect Herpes Simplex Virus-1 latency, in many latent or chronic infections this is a response to avoid pathogenic T-cell activity and damage. In chronic infections, it is the axis leading to CD8 dysfunction. As its bigger, nastier brother, Galectin-9 has a paradoxical role. It can both progress sepsis, but it also prolongs survival depending on the septic model you use.

The biggest problem is the effects of this axis on cancer. It can promote an immunosuppressive environment for tumor growth. Gal-9 expression and secretion are promoted by interferon β and γ, and high Gal-9 expression correlates with poor prognosis in multiple human cancers, and acute leukemia too. If you don’t recall, Interferon-Gamma is quite abundant in Omicron infections, but it is the de facto “proudest achievement” of the vaccines.

TIM-3 has roles in kidney disease and liver disease. TIM-3/Gal-9 interaction induces IFNγ-dependent IDO1 expression in acute myeloid leukemia blast cells. And as a last addition.

With the context of the articles published this year in this Substack, you now have a broad picture of my sustained concern regarding widespread infections, how even the “mild” Omicron infections helped create a cascade of other diseases, and why now you can see or read many “influencers” asking what is going on with their unvaccinated family members and friends.

These are just some notes I had written down. I used to think Omicron was “designed” by a group of white hats, “the good guys”, but now I have revisited that perspective. Even in the event this was the case, the fact remains that Omicron was serially passaged in immunocompromised hosts. The virus couldn’t grow forever, so now it wants to evolve to “stay forever”.

I got permission from the individual below to post this excerpt of our conversation.

Do you want to know the biggest irony of it all ? LPS can bind to a myriad of mycotoxins and create a synergistic inflammatory reaction, one potentiates the other. Also remember, SARS-CoV-2 is NOT able to replicate in T-Cells, in the rare case it infects them, it kills those cells, most CD4. Tim-3/Gal-9 takes care of CD8.

It is the reason I like calling it “PAID”, Paradoxical Acquired Immune Dysfunction. Because the virus makes your immune system, paradoxically, kill its own cells, and it is dysfunction because, for the most part, it is “fixable”. To a point. We have an upper limit of how many Naive T-cells we can produce through life, every single time naive or memory cells die, the body needs to churn many to compensate.

This has been my biggest concern since early 2023. Omicron bypasses the vast majority of our antibody response when it changes enough, and we all rely heavily on T-Cell response to avoid severe disease, and it now not only causes levels of dysfunction, but it can evade roughly 30% of our T-Cells. SARS-CoV-2 was never a short-term problem alone, it is everything else’s best friend, now a even better friend to everything else in the microscopic arms race against our immune system.

In case you are the anxious or worried type, my suggested supplements still protect you, the trick is finding the correct dosage for YOUR situation, recovering fast, and avoiding the loop of Covid > weeks later weird infection > weeks later bacterial infection > weeks later another weird thing > weeks later a “flu” > repeat step one. And I believe while the Spike is now heavily changed, it still persists, to what level, we don’t know.

Now it would be a shame if the virus also completely wrecked our most important antioxidant system… (this is called foreshadowing for the next article hehe. Glymphatic System Part II).

If you decide to become a paid subscriber at any time, or is one, a big thank you.

Live reaction when people tell me my articles helped them