The "Covid brain" and zombie cells

The coming cognitive decline "epidemic"

As a goal to help more people understand incredibly complex topics, this will be parts science and part descriptive language, sprinkled with a little recent history. First, a news article making the rounds, and quite a decent one at some levels.

Can’t Think, Can’t Remember: More Americans Say They’re in a Cognitive Fog

Adults in their 20s, 30s and 40s are driving the trend. Researchers point to long Covid as a major cause.

There are more Americans who say they have serious cognitive problems — with remembering, concentrating or making decisions — than at any time in the last 15 years, data from the Census Bureau shows.

The increase started with the pandemic: The number of working-age adults reporting “serious difficulty” thinking has climbed by an estimated one million people.

About as many adults ages 18 to 64 now report severe cognitive issues as report trouble walking or taking the stairs, for the first time since the bureau started asking the questions each month in the 2000s.

2021 was a highly productive year in regards to discovering significant pieces of the puzzle, that would later fit into other pieces, leading to a small picture of the whole picture. Given my personal history of lots of brain and nervous system “stuff” one of my primary interests has always been anything that affects cognition.

Thus such a journey inevitably led me to the Kynurenine Pathway, and by executing analysis using my framework I was able to forecast a lot of events to unfold at a biological level, and one of them was the impending increase in depression and cognitive impairment.

Of course, it is not “just” one aspect of this, all parts contribute, the lockdowns, the stress, the societal divide, and the literal brain damage social media caused (and still does btw), the economy, and all else. But the virus has been, and will always be the biggest “Hit and Runner”, accelerating every potential secondary dynamic. Far from me to feed the doom and gloom cycle, sadly this trend won’t improve any time soon

The cognitive decline is one of the main reasons I am vehemently pro-AI, and have been open about this aspect for a while.

This leads to the following two papers, somewhat connected.

Post-Vaccination Syndrome: A Descriptive Analysis of Reported Symptoms and Patient Experiences After Covid-19 Immunization

Results: The median age of participants was 46 years (interquartile range [IQR]: 38 to 56), with 192 (80%) identifying as female, 209 (87%) as non-Hispanic White, and 211 (88%) from the United States. Among these participants with PVS, 127 (55%) had received the BNT162b2 [Pfizer-BioNTech] vaccine, and 86 (37%) received the mRNA-1273 [Moderna] vaccine. The median time from the day of index vaccination to symptom onset was three days (IQR: 1 day to 8 days). The time from vaccination to symptom survey completion was 595 days (IQR: 417 to 661 days). The median Euro-QoL visual analogue scale score was 50 (IQR: 39 to 70). The five most common symptoms were exercise intolerance (71%), excessive fatigue (69%), numbness (63%), brain fog (63%), and neuropathy (63%). In the week before survey completion, participants reported feeling unease (93%), fearfulness (82%), and overwhelmed by worries (81%), as well as feelings of helplessness (80%), anxiety (76%), depression (76%), hopelessness (72%), and worthlessness (49%) at least once. Participants reported a median of 20 (IQR: 13 to 30) interventions to treat their condition

Conclusions: In this study, individuals who reported PVS after covid-19 vaccination had low health status, high symptom burden, and high psychosocial stress despite trying many treatments. There is a need for continued investigation to understand and treat this condition

As some of you may know I am not very fond of credentialism, I prefer the evidence speaking for itself rather than the people or institutions it comes from, alas, this study was done by Yale doctors. Nobody from an Ivy League institution would risk their reputation for no reason.

One of the limitations of this study is that it relies on self-report, while Post-Vaccine Syndrome is real (it is just a formal way of addressing vaccine injury, and the correct way too), self-reporting is subjective. A massive step forward nonetheless. The list and percentage of people experiencing symptoms.

One of the most pertinent aspects is how long the symptoms reported are present, from 417 to 661 days. There is a considerable correlation between PVS symptoms and Post-Viral Syndrome such as ME/CFS and Long Covid. Any sort of issue arising from exposure to Spike Protein will inevitably end up being extremely complex to dissect, otherwise, I wouldn’t have spent thousands of hours on this endeavor alone.

But we can infer much from the self-report itself. One of the core issues resides in how the Spike Protein, with or without Endotoxins, can engage with different receptors to shift the cell and systemic metabolism. Production of Spike (mRNA → cell → Spike production = massive amounts of inflammation) also induces the same, and the list goes on.

Simply put, while the initial hit and the middle of the journey may be distinct, the end of the road is the same. Excess inflammation, excess ROS, mitochondrial dysfunction → The Kynurenine Pathway. Also, a major player in cardiovascular problems, which many of the symptoms described can be a byproduct of.

Many of the molecules involved in the Kynurenine Pathway play a dual role, they can help while “costing” you something, but when the equilibrium is lost, they become toxic molecules to your nervous system and your brain.

The changes in kynurenine pathway in neuropathic pain within the central nervous system. Under physiological conditions (top panel) there is a balance between neuroprotective KYNA produced by astrocytes and neurotoxic QUIN produced by microglia. In neuropathic pain (bottom panel), activation of microglia and infiltration of peripheral macrophages occur; therefore, as a consequence, the balance between KYNA and QUIN is disturbed.

Before covering the next subject, it is worth noting that all participants reported attempting some sort of supplementation to ameliorate their symptoms, with probiotics being used by the majority of them. One of the reasons I don’t just suggest people use probiotics blindly, they are costly and can be of no effect if you don’t know what is going on in your gut. No harm in supplementing, and probably some benefit, but in complex cases such as these, it is an expensive hit or miss.

The following article talks about the KP and has another 4 articles on the subject. I will also quote the first important paragraph from that article.

SARS-CoV-2 hijacks the Kynurenine Pathway

While you can modulate the receptor we are about to discuss, it is too important to “mess with”, and there is extensive evidence of the positive effects of modulating the Kynurenine Pathway itself.

Fasting, being in Ketosis.

NAC+Glycine
Pyridoxine (Vitamin B6) (Thanks Paul)
Thiamine (although very indirectly)
Melatonin (directly, such as B6 and GlyNAC)
Metformin (possibly Berberine)

But above all else the best Tryptophan/KP fix is EXERCISE.

Basically, the supplements and steps I suggest for dealing with SARS-CoV-2 and many other conditions.

Not originally in the article: You can also modulate the KP with a myriad of other methods, but these are the ones I had more success with.

In addition to this suggestion, if you want or need to deal with senescence, one of the best options, and superior to Quercetin, is Fisetin, it has a systemic effect on senescent cells and it is a primary part of my “vaccine recovery” article, it can be rather costly in many parts of the world. The second is Fucoidan, which arguably could be considered the best-recovering supplement for almost any condition, be forewarned, Fucoidan is very, very expensive. Lastly, Olive Leaf, and Olive Leaf Extract, especially for patients with endothelial issues (a significant part of Covid and vaccine damage have clinical and subclinical endothelial damage/dysfunction). And of course, as I recently wrote about it, long-term Taurine supplementation.

If one of the most significant aspects of SARS-CoV-2 is killing many of your immune cells, such as lymphocytes, another terrible byproduct is the complete opposite. Not killing, not even infecting, but creating zombie cells, formally known as “senescent cells”. A nice short video explaining zombie cells.

Senescence is the other side of the Inflammaging coin, reference to the Kynurenine Pathway can be found inside. The following paper is related to the subject here, but ironically enough it is “good news”.

Senolytic therapy alleviates physiological human brain aging and COVID-19 neuropathology

Aging is a major risk factor for neurodegenerative diseases, and coronavirus disease 2019 (COVID-19) is linked to severe neurological manifestations. Senescent cells contribute to brain aging, but the impact of virus-induced senescence on neuropathologies is unknown. Here we show that senescent cells accumulate in aged human brain organoids and that senolytics reduce age-related inflammation and rejuvenate transcriptomic aging clocks. In postmortem brains of patients with severe COVID-19 we observed increased senescent cell accumulation compared with age-matched controls. Exposure of human brain organoids to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induced cellular senescence, and transcriptomic analysis revealed a unique SARS-CoV-2 inflammatory signature. Senolytic treatment of infected brain organoids blocked viral replication and prevented senescence in distinct neuronal populations. In human-ACE2-overexpressing mice, senolytics improved COVID-19 clinical outcomes, promoted dopaminergic neuron survival and alleviated viral and proinflammatory gene expression. Collectively our results demonstrate an important role for cellular senescence in driving brain aging and SARS-CoV-2-induced neuropathology, and a therapeutic benefit of senolytic treatments.

Clarifications of terminology first.

• Senolytics are drugs or natural compounds that help the body clean out these zombie cells

• They have direct and indirect anti-inflammatory effects

• BOs, Brain Organoids, are small sections of the brain created in a laboratory using Stem Cells, they are important for research such as this one

The authors aged the brains for 8 months because it is the best time window to investigate the impact of senolytics, the dosage was once every 2 weeks for 1 month, and they tested Navitoclax and ABT-737 (BCL-2 Inhibitors), and Dasatinib plus Quercetin (D+Q).

The senescent cells in the BOs were mainly astrocytes (a type of brain cell that supports neurons) and to a lesser extent neurons (a type of brain cell that transmits signals). The senolytic drugs reduced the population of senescent astrocytes more than senescent neurons, with D + Q showing the most potent effect.

Next, they performed RNA sequencing, a technique that measures the expression level of many genes, and you can distinguish between the different types of RNA molecules present in the same. The senolytic drugs altered the expression of several senescence-associated genes, including some that are involved in the inflammatory process of aging and inflammation itself, however, each drug had a distinct effect, and some genes were more responsive to each drug.

For instance, SERPINF1 mRNA level was significantly repressed following ABT-737 administration (Fig. 2b) while D + Q did not modulate SERPINF1 gene expression but markedly supressed IL8, SERPINE1 and IL1A mRNA levels

D + Q had a more broad-spectrum effect, mitigating multiple proinflammatory pathways characteristic of cellular senescence including NF-κB and IFNγ signaling

The highlighted section should be the most significant one here, since NF-kB is the primary mechanism by which virus/spike induces systemic damage, and IFN Gamma incites multiple short and long-term cascades detrimental to long-term health, IFN gamma also plays a significant role in the Kynurenine Pathway.

D+Q combination had the most broad-spectrum effect, suppressing multiple inflammatory pathways and the mTOR pathway, which is one of the key regulators of cell growth and metabolism. The combination also reverses the gene expression of the 9-month-old BOs to levels similar to the 8-month-old BOs, according to a test that uses the gene expression of brains to estimate the biological age of the brain. Effectively meaning D+Q both clears senescent cells but also rejuvenates the BOs brains.

The gene expression changes induced by D+Q were very similar to the ones of known life-span-extending interventions such as caloric restriction and rapamycin use. Indicating D+Q combination promotes health by targeting cellular senescence and biological aging.

They further tested if SARS-CoV-2 and a few other viruses (Japanese encephalitis virus (JEV), Rocio virus (ROCV), and Zika virus (ZIKV)) were capable of inducing senescence, which they all did. SARS-CoV-2 itself caused senescence via DNA damage in the infected cells, DNA damage is another big contributor to creating zombie cells.

Not only does SARS-CoV-2 create zombie cells by infection, but it also creates them via the bystander effect, meaning the damage these zombies can transform other cells into zombies by the inflammatory damage they induce called SASP (Senescence-associated secretory phenotype), in this state the cells are undead but keep creating damage. Per the evidence at this point in time, Delta is the one most aggressive in this effect.

To close this section and paper, using senolytics reduced SARS-CoV-2 viral expression and its induced senescence in BOs, followed by using the same treatment in vivo (mice) and finding that both D+Q or fisetin significantly improved the survival of the mice, and also showed a significant reduction in Covid “damage”. Meaning the senolytics also positively affected the lungs.


Now we go through what I usually do.

Senescence is associated with clots, excessive fatigue, sarcopenia, immune dysfunction, and cognitive impairment, in brain cells it is related to neuropathic pain, senescence can be triggered by chronic stress. In summary almost, if not every single symptom of “Covid brain” and PVS are a byproduct of complex interactions that end up creating zombie cells, and these are inflammaging best friends, creating an endless loop of long-term disease.

To connect those pesky dots. Herpes Simplex 1 can enhance senescence and inflammation in the brain by merely being in the region, thus accelerating neurodegeneration. Epstein Barr does the same but paradoxically is a defense mechanism against oncogenesis and immortalization of the cell. In a more complex context CMV, another Herpes virus does the same.

But above all else, nothing drives senescence and work together with every aspect described here than HERVs.

Endogenous retroviruses (ERVs) originate from integrated exogenous retroviruses and become part of the host genome during evolution. It now seems that they are hallmarks of aging and responsible for the spreading of cellular senescence in human.

Time is indeed a flat circle I guess.

If you chose to support this publication, thank you. You can also use Kofi as a one-time thing.