SARS-CoV 2 - Mitochondria, natural immunity, avian flu

And the Reverse AIDS hypothesis being proving right.

First, a paper a friend sent with really…intriguing finds.

Multiscale PHATE identifies multimodal signatures of COVID-19

Now, translating from bioinformatics to normal. By using a complex algorithm, a “supercomputer” to go through all available data (a huge amount), they found that the exact pathway drives disease and severity.

This partially proves our hypothesis, sadly no research on the planet will do the same, or even similar with the vaccines. Maybe in 2 or 3 decades, if they even remember.

To sum it up, we are right. The hypothesis is pretty much a theory at this point. If you can do parallel analysis and parallel information processing, you can easily find these signals everywhere.

Reverse AIDS - Part IV

It’s hard to take in, especially for the scientists/doctors in the crowd. Talking about vaccines…

Medscape @Medscape

Antibodies derived from natural COVID infection are more abundant and at least 10x more potent than immunity generated by vaccination alone. That’s not something we should ignore, scientists say. ms.spr.ly/6010wnz9o

Long-standing institutions are now signaling the truth… they have been seeing the writing on the wall for weeks by now, and now they signal the alignment with “the people”. Do remember these, do not let these go by. We will be living with the damage and ripple effects of these past 2 years for decades to come.

Targeted Down Regulation Of Core Mitochondrial Genes During SARS-CoV-2 Infection

Defects in mitochondrial oxidative phosphorylation (OXPHOS) have been reported in COVID-19 patients, but the timing and organs affected vary among reports. Here, we reveal the dynamics of COVID-19 through transcription profiles in nasopharyngeal and autopsy samples from patients and infected rodent models. While mitochondrial bioenergetics is repressed in the viral nasopharyngeal portal of entry, it is up regulated in autopsy lung tissues from deceased patients. In most disease stages and organs, discrete OXPHOS functions are blocked by the virus, and this is countered by the host broadly up regulating unblocked OXPHOS functions. No such rebound is seen in autopsy heart, results in severe repression of genes across all OXPHOS modules. Hence, targeted enhancement of mitochondrial gene expression may mitigate the pathogenesis of COVID-19.

While generally considered an inflammatory disease, recent evidence suggests that SARS-CoV-2 infection also inhibits mitochondrial bioenergetics, and that mitochondrial inhibition can activate of the inflammasome. Thus, in infected individuals, mitochondrial inhibition may not only contribute to excessive cytokine production but may be particularly impactful for the heart and brain, since these organs are highly reliant on mitochondrial energy production

Another paper demonstrates that this is a disease that affects you on a bioenergetics level, as I, and many others, previously argued. I have stated for over a year (you can see in my 1000 subs special post, in my notes) that this was firstly a mitochondrial dysfunction disease, and many of the effects of the infection are a byproduct of it.

SARS-CoV-2 infected human monocytes exhibited elevated glycolysis, suppressed OXPHOS, induced mROS production, increased hypoxia inducing factor 1-α (HIF-1α), up regulated HIF-1α target genes, increased viral load, and mRNA expression of IL-1β, IL-6, TNF and interferons. Treatment with 2-DG reduced viral load; and treatment with the OXPHOS complex V (ATP synthase) inhibitor, oligomycin, increased viral load and cytokine mRNA levels. Treatment with ROS scavengers N-acetyl cysteine (NAC) and MitoQ decreased HIF-1α protein levels, mRNA expression of pro-inflammatory cytokines, glycolytic and mitochondrial proteins, and viral load

This paragraph explains aspects and pathways of the infection, the virus uses more sugar, suppresses “energy generation”, increases the production of “cellular rust inside the mitochondria”, and up-regulated HIF-1α , which sets off the cascade of inflammatory signaling you are tired of hearing about. Treatments are discussed.

This is why some doctors, especially critical care patients lately, are having a huge success with Nicotinamide Mononucleotide to rescue patients at death’s door. It helps with exactly that.

This is precisely one of the reasons I recommend Niacin (flush type) for people, especially after infection, it is very helpful, and can be symptoms changing (from worse to almost normal pretty quick), as a cheaper form of Nicotinamide Mononucleotide.

I expect Long Covid, Long Covid post-vaccine and many of the problems of vaccinated can be tied down to this too, this pathway can exert a massive influence on your immune responses.

Hence, COVID-19 inhibited transcription of bioenergetic genes in the autopsy heart, kidney, liver, and lymph nodes. Selected genes participating in mitochondrial OXPHOS, fatty acid and amino acid metabolism, protein import, mitochondrial dynamics, and molecular transport were repressed several log-fold in the heart, as they were in the nasopharyngeal samples (Fig. 2D, Fig. S2), and to a lesser extent progressively in the kidney, liver, and lymph node. By contrast, in the lung OXPHOS genes were coordinately induced.

This human COVID-19 gene expression data indicates that SARS-CoV-2 infection initially impairs mitochondrial gene expression in the nasopharyngeal tissues and then progresses to down regulation of mitochondrial gene expression in the heart, kidney, and liver leading to death.

And since we are talking about bioenergy.

ACE2 pathway regulates thermogenesis and energy metabolism

Another aspect of the bioenergetics of the SARS-CoV-2 infection is the following. Down-regulation of ACE2 happens, and therefore you have a worsening of metabolic diseases, therefore affecting the mitochondrial function even more.

This post has more about mitochondria and SARS-CoV-2.

Bio Briefing—SARS-CoV-2, senescence and mitochondrial dysfunction

Four doses of the inactivated SARS-CoV-2 vaccine redistribute humoral immune responses away from the Receptor Binding Domain

However, a greater suppression on the induction of overall Neutralizing antibodies (NAbs) and NAbs targeting the receptor-binding domain (RBD) was found in participants with stronger immune responses after the 3rd dose. As a result, a stepwise elevation of RBD-NAbs from the 1st to the 3rd vaccination achieved a “turning point”. The peak RBD-NAbs level induced by the 4th dose was inferior to the peak of the 3rd dose. Accompanied with reduced induction of RBD-NAbs, the immune system shifted responses to the nucleocapsid protein (NP) and the N-terminal domain (NTD) of the spike protein. Although NTD directed antibodies are capable of neutralization, they only compensated the loss of RBD-NAbs to ancestral SARS-CoV-2 virus but not to the Omicron variant due to a substantial conformational change of Omicron NTD. This longitudinal clinical study monitored the immune response of the same cohort for every doses, shaping a relationship between the trajectory of immune focus and the dynamics of the neutralizing potency against the evolving virus. Our data reveal that immune responses could not be endlessly elevated, while suppression of heightened immune responses focusing on one subunit together with a shift of immune responses to other subunits would occur after repeated vaccination. Thus, an updated vaccine with more diverse epitopes capable of inducing NAbs against VOCs would be a future direction for boosters.

I found this paper fascinating, it uses the (less harmful in my opinion) inactivated vaccines. They found out that, even using the entire (dead) virus, you can’t continuously boost immune response.

After 3 doses, the immune responses were not only lower to the RBD shifted away from it, and towards the N and NTD protein, and as expected if you read the last virus post, the antibodies to said parts only worked with the ancestral strain, and not Omicron, because Omicron is too antigenic different than all other “variants”.

The paper goes in-depth about the changes, but this paragraph caught my eyes. You can not boost or vaccinate your way out of this, especially with Omicron, even the less harmful inactivated vaccines still have the drawbacks, and I still think they can be potentially dangerous short-term, and long-term (they will never protect you against new variants).

Our results may provide several implications for the booster dose aiming to strengthen the protection against VOCs, such as Omicron. First, an urgent use of current inactivated vaccines for the 4th booster is feasible but not ideal. Second, other types of vaccines may also suffer from RBD-NAbs suppression and shift of immune responses after repeated vaccination if the sequence keeps unchanged.

For last, something I have been tracking for over a year, starting with this post, which has a link to one of my 3 Twitter threads about this, and both Global Protein Insecurity I and II.

China reports four additional human H5N6 avian flu cases, one death

Not only a high pathogenic strain of avian flu has been spreading around the globe for over a year, and fracturing, creating local constraints and imbalances on the global protein market, but it has also been adapting to human transmission, slowly but surely.

Make no mistake, for months I have been saying this is my main concern. Any form of a human pandemic of avian flu will wipe out a third of the global population. The vaccinated third.

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