Lifestyle Genomics Research Centre – Lifestyle Genomics Research Centre

LONG COVID

More than a year after the outbreak of COVID – 19, 376,000 people in the United Kingdom reported symptoms such as excessive tiredness and other symptoms that are comparable to post-viral fatigue syndromes and ME/CFS (Chronic Fatigue Syndrome.

Despite the fact that most people recover rapidly, some individuals experience symptoms that continue for weeks or months after the illness has gone away.

“A sizeable subset of COVID-19 patients continues to experience chronic persistent symptoms even after recovery from acute infection, such as extreme fatigue, shortness of breath, joint pains, brain fog, and mood swings (2–4). These symptoms persist beyond the acute presentation of the disease and appear to be independent of disease severity. These long-haulers present with a disease portrait distinct from the typical acute COVID-19 disease. They broadly represent patients who have failed to return to their baseline health post-acute COVID-19 infection. >R<

The Long COVID section of your report lists variants on the genes that play a viral defense role in the immune system and are, at the same time, connected to Chronic Fatigue Syndrome and ME (Myalgic encephalomyelitis).

These variants were included based on the premise that CFS is caused by a viral infection that the body is unable to regulate. This would lead to prolonged inflammation and oxidative stress.

An increase in inflammation and an increase in oxidative stress would cause mitochondrial capacity for energy synthesis in the form of ATP to decline.

The suggested pathophysiological mechanism behind this phenomenon would mean an increase in inflammation and a decrease in antiviral activity.

As a result, the virus, or its components, might stay in the body, causing tissue damage and chronic inflammation.

Persistent inflammation which cascades into excessive free radical production (oxidative stress) can lead to mitochondrial damage.

Damaged mitochondria signal activation of the NLRP3 inflammasome which then triggers production of the inflammatory immune components like IL-1 and IL-18 >R<

This kind of vicious loop locks cellular mechanisms into an emergency mode with self perpetuated damage – repair or replace cycle which can steer cellular functions away from their normal, metabolic activities.

A research published in May 2021 adds additional insight on the similarities betweenLong-COVID, ME/CFS, and chronic viral exhaustion.

According to the findings, 67% of long-term COVID patients had Epstein-Barr virus titers that had reactivated, in comparison to only 10 percent in the control group. These symptoms (fatigue, cognitive fog, sleep disturbances, aches and pains in various parts of the body and skin rash) are also seen in Epstein-Barr virus (EBV) patients. >R<

The concept of a post viral syndrome isn’t new and multiple research studies have described a well known set of symptoms that usually involves significant fatigue, muscle pain, brain fog, which occurs after infection with Coxsackie virus, brucellosis, poliovirus, viral meningitis, Ross River virus, and Epstein-Barr virus. .>R<, >R<, >R<

Another research study found that about 17% of COVID-19 patients continued to have fatigue symptoms after their illness. About 3% met the criteria for CFS/ME. To try an distinguish whether the symptoms may be attributed to other traumatic events, the researchers also included PTSD in the study and found no overlap between patients with PTSD and CFS/ME. >R<

Going back to the SARS CoV-1 outbreak, in 2011, a short research looked at the parallels between chronic post-SARS (SARS-CoV-1) and fibromyalgia patients.

The study discovered that those with chronic post-SARS exhibited persistent fatigue, muscular discomfort, weakness, sadness, and non-restorative sleep — symptoms that coincided with those diagnosed with fibromyalgia and ME/CFS. >R<

OTHER POSSIBLE LONG COVID MECHANISMS

Another theory is linked to a study of upregulated genes in people with long COVID, which showed that platelet-related pathways were downregulated and genes involved in transcription, translation, and the cell cycle were upregulated.

The downregulation of platelet-related genes (e.g. platelet factor 4, coagulation factor XIIII) may correlate with the thrombocytopenia (low platelet count) seen in COVID-19 patients and be a source of fatigue. Interestingly, the researchers also identified interferon-related genes as being downregulated.

When a mitochondrion is no longer functioning correctly, it degrades and recycles via a process called mitophagy (autophagy of mitochondria).

In addition to activating the NLRP3 inflammasome cascade (IL-1 and IL-18), damaged mitochondria can trigger interferons and other pro-inflammatory cytokines. Specifically, when mitochondrial DNA leaks, it triggers the immune response, including interferon activation, as a danger signal from the damaged mitochondria.

Some viral infections also trigger mitophagy, or mitochondrial destruction, which works to help the virus evade the immune response.

Thus, we have immune system activation causing mitochondrial damage as well as mitochondrial damage-causing immune system activation. In a trap of decreased cellular energy, fatigue persists.

Gut Health

According to Nature, two research teams have published findings that suggest SARS-CoV-2 fragments can linger in the gut for months after an initial infection.

“The findings add to a growing pool of evidence supporting the hypothesis that persistent bits of virus – coronavirus “ghosts”, as Stanford Medicine oncologist and geneticist Ami Bhatt has called them, linger on in the body months after “recovery” from infection.”

We touched on this issue in our June ’21 Facebook post, following a similar Harvard report.

COVID-19 and ARDS (Acute Respiratory Distress Syndrome)

Acute respiratory distress syndrome (ARDS) is a result of a viral pneumonia caused by the SARS coronavirus 2 (SARS-CoV-2) infection. Viral pneumonia and ARDS symptoms coexist in their presentations, making severe COVID-19 a hybrid condition. >R<

In patients who are severely sick, acute respiratory distress syndrome (ARDS) is a condition in which oxygen levels drop, fluid accumulates in the lungs, and positive pressure ventilation is required. Lung tissue damage from an unchecked inflammatory reaction is the cause of ARDS.

Fluid escapes into alveoli in ARDS because the epithelial cells lining the alveoli are no longer securely linked together. The gas exchange is halted as soon as the alveoli fill up with the spilled fluid. As a result, the amount of oxygen in the air is reduced, while the amount of carbon dioxide in the air increases.

In critical care units, ARDS goes unnoticed much too often. As many as 42% of patients with COVID-19 pneumonia and 61%–81% of those needing intensive care develop acute respiratory distress syndrome (ARDS). After the beginning of symptoms, the median time to intubation in Singaporean patients is 8.5 days. There have been earlier cases of ARDS developing on days 8 or 9 after the beginning of symptoms. Because of this, individuals with COVID19 infection should be closely monitored for the emergence of ARDS. >R<

Apart from the genetic component, there are several environmental and lifestyle factors that increase the susceptibility to ARDS, as well as some medical conditions: air pollution, age, right ventricular dysfunction, immunosuppression, alcohol abuse, and smoking can all contribute to ARDS.

Your report includes genetic components involved in a number of different viral recognition patterns in the body that recognize the virus and then trigger several different mechanisms of inflammatory cytokine release.

The body’s innate immune response must be managed so that it does not overwhelm it. Patients with COVID-19 may have “a variety of immunological reactions” as well as “the generation of cytokine storms in the body,” which may be linked to their very ill state if their infected lung cells aren’t removed.

Coronaviruses and SARS vs. SARS-CoV2

Coronaviruses are a large and diverse viral family. They have a wide host range, including humans.

Coronaviruses cause both COVID-19 and SARS. SARS-CoV is the virus that causes SARS, whereas COVID-19 is caused by SARS-CoV-2.

Human coronaviruses typically cause mild respiratory infections such as the common cold. Human coronaviruses account for 10 to 30% of upper respiratory tract infections in adult individuals. >R<

SARS is the name given to the respiratory sickness caused by SARS-CoV. SARS is an abbreviation for severe acute respiratory syndrome.

It was discovered for the first time in 2003.

From late 2002 to mid-2003, there was a worldwide SARS outbreak. During this time, almost 8,000 people became infected with the virus, and 774 died. >R<

One of the initial indications of SARS is fever. Other symptoms may accompany this, such as: cough, malaise, or exhaustion; aches and pains in the body;
shortness of breath and headaches.

Respiratory symptoms can deteriorate, resulting in serious symptoms advancing quickly, leading to pneumonia or respiratory failure.

COVID-19 and SARS are comparable in many aspects.

Both are coronavirus-caused respiratory illnesses that are transmitted by respiratory droplets produced when a person with the virus coughs or sneezes.

The transmission can also occur through contact with objects or surfaces containing the virus. >R<

Both infections can lead to potentially serious illness, sometimes requiring oxygen or mechanical ventilation can have worsening symptoms later in the illness.

Both of these coronaviruses have similar at-risk populations, including older persons and those with pre-existing medical issues.

The novel coronavirus also shares 79 percent of its genomic sequence with the SARS virus. >R<

Although SARS-CoV-2 is more closely related to bat coronaviruses in general, the receptor binding site is more comparable to SARS-CoV.

SARS-CoV-2 and SARS-CoV use the same host cell receptor, according to a new study. It was also shown that the viral proteins needed for host cell entrance attach to the receptor with the same tenacity in both viruses – they have similar affinity. >R<

Despite these similarities, there are also some significant distinctions between the two:

SARS cases were often more severe. It is estimated that 20 to 30 percent of people with SARS needed respiratory support and ventilation. >R<

The fatality rate of SARS is higher than that of COVID 19.

The expected mortality rate is around 10%, with mortality rates as high as 45% in particular patient populations. >R<

SARS-CoV-2 seems to be more easily transferred than SARS-CoV.

One theory is that the volume of viral load is greatest in the nose and throat of patients who have COVID-19 immediately after symptoms emerge.

With contrast, in SARS, virus loads peaked relatively late in the infection.

People infected with COVID-19 seem to shed the virus earlier than people infected with SARS, although there haven’t been any confirmed cases of SARS CoV transmission prior to the onset of symptoms.

In another study, researchers compared the part of the viral protein that binds to the host cell receptor. The study also discovered that SARS-CoV-2 has a receptor binding site that binds to the host cell receptor more strongly than SARS-CoV. >R<

On the point of cross immunity to SARS CoV-2 because of an earlier acquired immunity to other coronaviruses, previous studies have found that about 40–50% of the population has cross-reactive T-cells, most likely as a result of another coronavirus exposure in the past.

According to German research, even if COVID-19 patients did not produce antibodies, the majority of them elicited a T-cell response.

The study also discovered that T-cells from previous coronavirus exposure cross-reacted with SARS-CoV2 in about 80% of the control group (patients without COVID-19). Although this cross-reactivity may not provide complete immunity for everyone, it may help to alleviate symptoms. >R<

TLR7 GENE AND COVID-19

TLR7 (toll like receptor 7) is an innate immune system sensor in charge of finding single-stranded RNA and it is therefore one of the ways that our immune systems recognise SARS-CoV-2 as a pathogen.

TLR7, an immune system-related gene, was found to have an uncommon mutation in a genetic investigation of young individuals in their 20s and 30s, with severe instances of COVID-19 (one of which resulted in death) .>R<

Most often a loss in TLR7 function may decrease viral protection and increase severity of viral infections. An overactive TLR7, however, may increase chances of developing lupus.

There are common genetic variants which ca either decrease or increase TLR7 function.

The TLR7 genetics seem to have a severe, inhibitory impact on the production of Interferon type I which can cause much lower antiviral response of the innate immune system and impair its’ key role in fighting off viral infections at the right time.

TLR7 mutations proven to have this effect are most likely the reason why only a small subset of the young and healthy population end up as severe Covid-19 cases. /R/

When researchers examined some of the B cells from young and otherwise healthy males with severe Covid-19, it turned out that these patients’ B cells failed to respond to stimulation of TLR7. This could also potentially help to explain why most of younger patients who end up with severe Covid-19, are male. /R/, /R/

PRETOX: PREPARE FOR DETOX & CLEAR OUT THE EXCRETION ROUTE

Successful detoxification SHOULD be based on communication between THREE phases of biochemical signalling. In this sophisticated process, toxins are removed from inside cells, through cellular membranes, into the lymph and extracellular matrix. They are moved through bile into the gut or from lymph and bloodstream through kidneys. All of this is fulfilled by transport or carrier proteins that bind with toxic conjugates passed on from phases II and I.

This complicated system HAS to be addressed in a reverse order to significantly lower the chances of failure or serious side effects. So made you a favour by placing this section in the right place in your report so you can avoid the most common mistakes in addressing detoxification.

Categories listed here include Kidney Health, Bile Flow, Extracellular Matrix proteins and Multi-Drug resistant proteins (the transporter proteins mentioned above).

TIP: Tackling gut-level pathogens will curb GI inflammation and free up the transporter proteins necessary to remove toxic conjugates via Kidneys, Bile and Extracellular Matrix. This section of your report will focus on ensuring that your body’s drainage system and excretion routes are not “clogged up”. This will also open up phase II detoxification pathways, to make sure that when you address them directly, they can work in their highest capacity.

PREPARE YOUR TERRAIN

Phase One : PREPARE YOUR TERRAIN

The aim of the first section of your report, is to identify your genetic predispositions towards environmental dietary and lifestyle triggers, which can drive inflammatory processes in your body.

This part of your report will address DNA data-based reasons to justify possible changes worth implementing, in order to get your journey to optimal health started.

The primary goal here, is to decrease the load caused by external factors contributing to inflammation, and by measures which you can immediately start controlling. In short – remove yourself as much as possible from the inflammatory environment or remove the inflammatory environment from your surroundings.

Many diseases stemming from chronic stress and inflammation have early warning signs, meaning some cases can be prevented, or improved with lifestyle changes which help manage stress, diet, daily lifestyle choices, and in general by avoiding the environment that you may not be wired so well to handle.

Food allergy or intolerance symptoms can range from inflammation and swelling, to weight problems, digestive issues, aches and pains, mood and cognitive changes, fatigue and more. Inflammation is your body’s immune defence system working to remove something harmful from your system. This part of your report will highlight for you, genetic factors behind sensitivity to most inflammatory foods or food compounds, such as wheat, lactose, fructose, gluten, peanuts, shrimp and food additives and oxalates.

Results for Variants associated with your body’s ability to handle alcohol, caffeine and coffee could perhaps influence your decision-making process, or prompt you to provide your body with extra support and recovery aids, when you treat yourself with substances or beverages that are intended to provide a level of pleasure, but can in fact be more harmful for some compared with others.

Ketogenic Diet

For some time now, the Ketogenic diet has been touted for its anti-inflammatory properties and effects. Whilst a correct implementation of this regimen can most definitely benefit many undertakers, it can also be a double-edged sword to others, and here, your genes can also play a role. It may however, have to be a personalised decision to figure out if your metabolism needs extra support or maybe another approach altogether.

Glucose, Cholesterol and Triglycerides

High blood sugar and connected metabolic disorders drive up inflammatory conditions. Dysfunctional glucose and fat metabolism can impair our immune systems, cellular energy production and accelerate cellular oxidation and ageing.

Metabolic syndrome, characterised by abdominal obesity, insulin resistance, hypertension, and hyperlipidemia, is considered a major health hazard and has been called one of the great challenges of our times.

The relevant categories we’ve listed here will bring to your attention some possible weaknesses in how your biology is designed to react to sugar, fats and cholesterol content in your diet. It can also help you analyse to what extent your genetic blueprint has equipped you to handle good vs. bad cholesterol, which will hopefully help you establish dietary habits that are more in tune with your body’s capacity to use these molecules to your advantage. Genetic variants linked to Triglyceride status may additionally shed more light on your recent lab results, and help you figure out not only what to avoid, but also what to include, in order to improve your metabolic profile.

Fatty Acids Metabolism

The correct balance between fatty acids as well as their levels have potent anti-inflammatory effects, and they may be beneficial for a range of inflammatory conditions if the right balance is maintained.

Studies show that dietary supplementation with fish oil, lowers the activity of chronic inflammatory and autoimmune diseases, including Rheumatoid Arthritis, Crohn’s disease, Ulcerative Colitis, Psoriasis, Lupus Erythematosus, Multiple Sclerosis, and more. On the other hand, imbalanced Omega 3 to Omega 6 ratios, or deficiencies of one or the other, have been implicated in some inflammatory processes and negative outcomes in some conditions. The way your body promotes the production of one fatty acid vs. the other is blueprinted into your DNA, and gaining this information may help you be more precise in using these powerful molecules in a way that will be tailored to your personal needs.

Environmental Exposures

There are a few specific toxic compounds which we were able to tie to genetic variants, and have therefore listed them in your report. We’ve picked these, because our environment and lifestyles mean it is easy for us to consume or interact with them. The available research has naturally turned this section of the report into a valuable source of personalised information, which may be used in prenatal care and family planning.

Pesticides – although our biology is equipped with pathways which handle these toxic compounds, their primary role is not, in fact, to do that. As such, these mechanisms whose primary function would be to ensure healthy cellular procecesses, have to divert their already genetically capped flow, to deal with foreign substances, that do not belong in the cellular environment.

A systematic analysis of the peer reviewed literature, showed an association between prenatal organophosphates exposure and PON1 SNP, with neurobehavioural health outcomes. It linked organophosphate pesticides to neurotoxic and genotoxic effects. Ref.

We have also listed genetic variants connected to poorer cognitive function in people exposed to higher levels of Mercury. Through fish consumption by their mothers, when they were featuses, as well as variants linked to higher mercury levels in pregnant women who consumed fish.

Obviously, there are more routes of mercury exposure, like dental amalgams for example, so this information could be helpful for people contemplating decreasing toxic load on their bodies, by making changes to their dental health.

Similar to pesticides, our bodies were not also designed to have to cope with plastic particles and BPA. The closest chemicals resembling these synthetic structures, are in fact human sex hormones. The pathway that was naturally responsible for hormonal metabolic processes, now has to engage with other chemicals therefore, that do not necessarily belong there. Combine this with polymorphisms, which make some detoxification enzymes in these pathways less abundant, and we may have a recipe for conditions linked to a build up of hormone intermediates, which are toxic and are not being excreted from our bodies at the rate they should be.

Aflatoxin B1 is a highly carcinogenic mycotoxin, which is a product of certain moulds that can be present on some of our favourite snacks and foods like peanuts, sweetcorn and some grains. Children are particularly affected by aflatoxin exposure, which is associated with stunted growth, delayed development liver damage, and liver cancer. An association between childhood stunting and aflatoxin exposurehas been reported in some studies. International sources of commercial peanut butter, cooking oils (e.g. olive, peanut and sesame oil), and cosmetics have been identified as contaminated with aflatoxin.

We have listed variants that make one especially vulnerable to DNA damage due to Aflatoxin B1, and the same variant has also been associated with Hodgkin Lymphoma. Ref Ref.

The variant in question belongs to a gene responsible for DNA repair. This information could perhaps be beneficial for people affected by this SNP, in terms of extra steps that need to be taken to improve food preparation hygiene. For example, heating and cooking under pressure can destroy nearly 70% of aflatoxin in rice, compared to under atmospheric pressure only 50% is destroyed.

Closing the first section of your report is a list of genetic variants linked to coping with stress and response to traumatic events.

Stress management can no longer be considered a complementary approach; it is an essential therapeutic strategy, and it is becoming abundantly clear that dealing with past or recent trauma as well as the ability to manage present stress load, absolutely has to go in tandem with any other interventions.

This couldn’t be more important in view of the most recent developments on the world stage.

Anxiety disorders have been associated with immune-inflammatory disturbances Ref.^.

In a study designed to investigate both pro-and anti-inflammatory cytokines and their balance in patients with General Anxiety Disorders, in comparison to healthy controls, the findings indicated a relatively increased pro-inflammatory response and decreased anti-inflammatory response, which demonstrated an altered cytokine balance in General Anxiety Disorders. Although Cortisol is ordinarily anti-inflammatory and contains the immune response, chronic elevations can lead to the immune system becoming “resistant,”. An accumulation of stress hormones can translate into increased production of inflammatory cytokines, that further compromise the immune response balance. Ref.

SAMe Production

SAMe Production Diagram

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Author: Lifestyle Genomics Research Centre