by Daniel Brouse
email help@membrane.com
May 30, 2021
COVID gets into your genes and makes alterations. Anybody that has “Long Haulers” (Post Acute COVID-19 Syndrome) can tell you about some of the resulting symptoms. COVID-19 Induced Secondary Pellagra (CISP) is one of the outcomes. CISP occurs when COVID changes your genome to chronically increase the breakdown of NAD+ and simultaneously decrease the production of NAD+ (nicotinamide adenine dinucleotide). NAD+ is in every cell and is involved in cell creation, maintenance, metabolism, and regulating cell processes. Without the ability to maintain NAD+ levels, the body’s immune system is severely compromised. For instance, you can not properly metabolize Vitamin C, Vitamin D, and zinc without NAD+. No matter how large of a megadose you take, it will not be metabolized; therefore, it will not be utilized in your immune response to any pathogen.
Not only will inadequate NAD+ levels impact your immune response, lack of NAD+ causes significant symptoms due to lack of cell regulation. A COVID NAD+ deficiency can cause a lack of serotonin regulation resulting in a lack of body temperature regulation. Dr. Ade Wentzel added, “NAD+ deficiency causes a lack of Tryptophan which is used for serotonin production and hence temperature…” Lack of cell and cytokine regulation also causes headaches, brain fog, anxiety, stress, loss of taste or smell, dizziness, fatigue, muscle aches, dermatitis, diarrhea, dementia, and death. Any activity that causes inflammation or a demand for NAD+ will result in more acute symptoms. Exercise and exertion of any kind exacerbates the condition.
The types of COVID-19 genome modifications are known as epigenetics. “Unlike genetic changes, epigenetic changes are reversible and do not change your DNA sequence, but they can change how your body reads a DNA sequence,” explains the CDC. At this time, we do not how many many genome modifications COVID makes nor how long the modifications will last.
Thousands of CISP patients have been treated successfully with a modified pellagra therapy; however, after a year of treatment, NAD+ production has not returned to normal for most patients.
In addition to genome modifications to NAD+, COVID also makes other changes. Brain fog, dizziness, tinnitus, ear aches, vertigo, and pressure in the ears are some of the symptoms associated with epigenetic changes in the upregulation of Indoleamine 2,3-dioxygenase (IDO). “IDO is an immune checkpoint molecule in the sense that it is an immunomodulatory enzyme produced by alternatively activated macrophages and other immunoregulatory cells. IDO is known to suppress T and NK cells, generate Tregs and myeloid-derived suppressor cells, and also supports angiogenesis.’ (Wikipedia)
Dr. Ade Wentzel said, “The epigenetic upregulation of IDO will determine the amount of quinolinic acid. Quinolinic acid comes from the kynurenine pathway. If the viscosity of the whole middle ear is increased then the ability to equalize will be less… same as having a cold. So, the ear isn’t equalizing correctly on increasing pressure. The same as when you land in a plane. If the viscosity in the semicircular canals is increased, the otoliths may well be lagging causing the vertigo. The otoliths usually “Float” in the semicircular canal and trigger tiny sensory hairs that allow you to detect position.”
It is possible that changes in the weather that cause changes in atmospheric pressure (Lows and Highs) may result in the same problems.
There are many other Epifactors and Transcription Factors caused by COVID. “Using integrative analyses of gene co-expression networks and de-novo pathway enrichment, we characterize different gene modules and protein pathways enriched with Transcription Factors or Epifactors relevant for SARS-CoV-2 infection. We identified EP300, MOV10, RELA, and TRIM25 as top candidates, and more than 60 additional proteins involved in the epigenetic response during viral infection that has therapeutic potential. Our results show that targeting the epigenetic machinery could be a feasible alternative to treat COVID-19.” (Nature)
“We found that exposure to the SARS-CoV-2 spike protein alone was enough to change baseline gene expression in airway cells,” said Evans who is based in the laboratory of Sharilyn Almodovar, Ph.D., at the Texas Tech University Health Sciences Center.
“This suggests that symptoms seen in patients may initially result from the spike protein interacting with the cells directly.”
The researchers analyzed expression in genes with functions related to oxidative and osmotic stress, cell death, the inflammatory response, and DNA damage, among others. They found that expression of CCL2, IL1A, IL1B, and MMP9 showed up to two-fold changes in expression after recovery.
All of these genes play a role in inflammation. CCL2 levels are increased in neuroinflammatory disorders such as epilepsy and Alzheimer’s, as well as in some autoimmune diseases like psoriasis, whereas MMP9 is needed for wound healing and recovery from lung damage.
IL1A and IL1B are part of the interleukin family of cytokines and directly produce inflammation and promote fever, as well as playing a regulatory role in the greater immune response. —
— Clinical OMICs
Structural analyses have elucidated hot spots in viral binding domains, mutations, and specific proteins in the host such as the receptor angiotensin-converting enzyme 2 (ACE2) and the transmembrane protease serine 2 (TMPRSS2) to be implicated in cell entry and viral infectivity. Furthermore, epigenetic changes that regulate chromatin structure have shown a major impact in genome stabilization and maintenance of cellular homoeostasis and they have been implicated in the pathophysiology of the virus infection. Epigenetic research has revealed that global DNA methylation along with ACE2 gene methylation and post-translational histone modifications may drive differences in host tissue-, biological age- and sex-biased patterns of viral infection. Moreover, modulation of the host cells epigenetic landscape following infection represents a molecular tool used by viruses to antagonize cellular signalling as well as sensing components that regulate the induction of the host innate immune and antiviral defence programmes in order to enhance viral replication and infection efficiency.
— Epigenetic mechanisms regulating COVID-19 infection (NIH)
“Viral proteins encoded by SARS-CoV-2 disrupt critical components of human cells’ molecular machinery and disable responses to infection. Researchers in the US describe how specific viral proteins bind to human RNAs involved in RNA splicing, protein translation, and protein trafficking, and in doing so suppress the host cell’s coordination of a key antiviral defense known as the type I interferon response.”
— SARS-CoV-2 Disables Key Components of Human Cells’ Defense System
“[COVID-19] interferes with protein trafficking to the cell membrane upon infection. Disruption of each of these essential cellular functions acts to suppress the interferon response to viral infection. Our results uncover a multipronged strategy utilized by SARS-CoV-2 to antagonize essential cellular processes to suppress host defenses.
— SARS-CoV-2 Disrupts Splicing, Translation, and Protein Trafficking to Suppress Host Defenses
COVID-19 genetic changes have been found to cause Reverse-transcribed SARS-CoV-2 RNA.
Prolonged detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA and recurrence of PCR-positive tests have been widely reported in patients after recovery from COVID-19, but some of these patients do not appear to shed infectious virus. We investigated the possibility that SARS-CoV-2 RNAs can be reverse-transcribed and integrated into the DNA of human cells…
— Reverse-transcribed SARS-CoV-2 RNA can integrate into the genome of cultured human cells and can be expressed in patient-derived tissues (PNAS)
How many different modifications to your genes does COVID-19 make? How long will the alterations last? We don’t know.
“Not all epigenetic changes are permanent. Some epigenetic changes can be added or removed in response to changes in behavior or environment.” Most of a person’s lifetime epigenetic changes have to do with aging. Infections and behaviors, like smoking, also can cause epigentic changes. Most of a smoker’s epigenetic changes revert back after a year of not smoking. Perhaps the COVID epigentic changes will go away over time. Unfortunately, COVID also does insertions. Insertions can not be reverted. The biggest unknown for COVID is the possibility — “if the insertion is in a tumor suppressor, for example, and disrupts that gene, then cancer can be a concern.”
Most experts are of the opinion that “the preexisting state may well determine the final outcome when there is genetic upregulation. COVID is choosing those that may well already have some subclinical symptoms of upregulated pathways.” In the case of cancer and tumor suppression, it appears COVID chooses people that have reduced P53 just like other coronavirus do (P53 is the tumor suppression gene.) Therefore, COVID is unlikely to cause insertions into the gene and be an additional cancer risk.
We do know there is upregulation of genes by COVID and these genes are related to abnormal T-cell, macrophage function, and abnormal humoral immunity. The epigenetic changes related to NAD+ have reverted in some cases after 13 months of treatment. The longer one has left it before getting help the harder and longer it takes for the epigenetics to revert. Currently, we are monitoring cases of epigenetic reversion as more people reach 12 months of treatment.
Post–COVID-19 Associated with Immune Cell Infiltration and Altered Gene Expression
COVID causes long-term immune dysfunction. “These findings indicate that T cell–mediated inflammation persists in the olfactory epithelium long after SARS-CoV-2 has been eliminated from the tissue, suggesting a mechanism for long-term post–COVID-19 smell loss.”
