bookmark_borderLong-COVID: What We Know About Long Haulers Syndrome

COVID=19
by Daniel Brouse
August 25, 2021
help@membrane.com

Post Acute Covid Syndrome 19 (PACS19), long-COVID, and Long Haulers Syndrome are names for the condition that an individual has after recovering from the SARS-CoV-2 virus. Long-COVID is actually a combination of several conditions and syndromes including changes to your genetics, an accelerant to aging, and the persistence of the virus in multiple organs for long periods of time.

The CDC Panel Report Long COVID Panel Survey found:

* 81% of adults with ongoing symptoms of COVID lasting three months or longer — or four out of five adults — are experiencing limitations in their daily activities compared to before they had the virus. (Economic implications include work force participation and long-term health care costs.)

* Young adults between ages 18 and 29 had the highest share of people currently with long COVID who have trouble performing daily tasks, at 86.3%. What will the long-term costs and quality of life be when these people are in their 50’s,60’s, and if they get to live into their 70’s?

There are over 60 proteins involved in the epigenetic response to COVID. So far out of these 60 proteins, three long-COVID epigenetic syndromes have been identified. There are likely many more. (The epigenetic changes are in addition to the organ damage caused by the virus.)

COVID-19 also causes other long term damage that we are still discovering.

Vaccines Help Prevent Secondary Complications
A study shows you are less likely to develop long-COVID Myocardial Infarction and Ischemic Stroke after a COVID-19 Infection if you ARE VACCINATED. Many people may not even know that COVID causes an increased risk of thrombosis. Vaccines can prevent secondary complications.

Association Between Vaccination and Acute Myocardial Infarction and Ischemic Stroke After COVID-19 Infection (Vaccines Help Prevent Long-COVID Complications)

Rogue Antibodies
Autoantibodies are antibodies (immune proteins) that mistakenly attack a person’s own healthy tissues and organs. A study published in Nature found “rogue antibodies involved in almost one-fifth of COVID deaths. The self-targeting antibodies attack type 1 interferons that play a key role in fighting infection. Antibodies that turn against elements of our own immune defences are a key driver of severe illness and death following SARS-CoV-2 infection in some people, according to a large international study. These rogue antibodies, known as autoantibodies, are also present in a small proportion of healthy, uninfected individuals — and their prevalence increases with age, which may help to explain why elderly people are at higher risk of severe COVID-19.”

Up to three percent of the population already has faulty genes that create these autoantibodies. Of those between the ages of 18 and 69, 0.18% had existing autoantibodies against type 1 interferon. “Autoantibodies were present in around 1.1% of 70- to 79-year-olds, and 3.4% of those over the age of 80.”

A follow up study, “New-onset IgG autoantibodies in hospitalized patients with COVID-19,” found “Coronavirus Disease 2019 (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection, is associated with many different clinical features that are commonly found in autoimmune diseases, including arthralgias, myalgias, fatigue, sicca, and rashes. Less common manifestations of autoimmunity have also been observed in COVID-19 patients, including thrombosis, myositis, myocarditis, arthritis, encephalitis, and vasculitis. These clinical observations, and the increasing proportion of “recovered” patients with persistent post-COVID-19 symptoms (so-called “long haulers”, or “long COVID”) suggest that inflammation in response to SARS-CoV-2 infection promotes tissue damage in the acute phase and potentially some of the long-term sequelae. A subset of autoantibodies targeting traditional autoantigens or cytokines develop de novo following SARS-CoV-2 infection.”

“The team also found that individuals with genetic mutations that disrupt the activity of type 1 interferons are at higher risk of life-threatening disease” suggesting COVID causes changes to the genes resulting in the creation of rogue autoantibodies.

In a study of healthcare workers, all had persistent autoantibodies, including ones that can cause chronic inflammation and injury of the joints, skin and nervous system. “We would not normally expect to see such a diverse array of autoantibodies elevated in these individuals or stay elevated for as long six months after full clinical recovery,” said Susan Cheng of the Cedars-Sinai Smidt Heart Institute in Los Angeles. (As reported in Paradoxical sex-specific patterns of autoantibody response to SARS-CoV-2 infection)

“We don’t yet know how much longer, beyond six months, the antibodies will stay elevated and/or lead to any important clinical symptoms,” Cheng said. “It will be essential to monitor individuals moving forward.” The team is investigating autoantibody elevations and their relationship to persistent symptoms in people with long-COVID.

NAD+ Deficiency
COVID both increases the breakdown of NAD+ and decreases the production of NAD+. “NAD regulates the inflammatory response in immune and non-immune cells through Sirtuins. Epigenetic regulation of histones and non-histone proteins is induced by sirtuins and is essential for the development, reprogramming, and differentiation of the immune system and its related pathologies. A deregulation of the NAD+ levels has been associated with metabolic diseases and aging-related diseases, including neurodegeneration, defective immune responses, and cancer.” — NAD-immune-system

The NAD+ deficiency results in a compromised immune system. The body can not properly metabolize vitamins nor mount a proper immune response. The NAD+ deficiency also resembles an autoimmune disease where the immune system appears to be attacking a healthy body. Without NAD+ regulating the immune system, the immune response becomes dysfunctional.

Though there is no cure for the NAD+ Deficiency Syndrome (CISP — COVID-19 Induced Secondary Pellagra), the symptoms can be treated with Niacin (Nicotinic Acid).

Upregulation of IDO
Indoleamine 2,3-dioxygenase (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.

Memory T cells are crucial for the immune system to remember how to fight pathogens. IDO is also related to the viscosity of body fluids and membrane function. 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.

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.”

Coronavirus Transforms Pancreas Cell Function
When COVID infects cells, it impairs cell activity and can also change their function. When insulin-producing beta cells in the pancreas become infected with the virus, they produce much less insulin than usual, and also start to produce glucose and digestive enzymes. “We call this a change of cell fate,” said study leader Dr. Shuibing Chen, who described the work in a presentation at the annual meeting of the European Association for the Study of Diabetes.

It is not clear whether the changes are long-lasting, or if they might be reversible, the researchers reported in Cell Metabolism, “SARS-CoV-2 infection induces beta cell transdifferentiation“. “Single-cell RNA sequencing and immunostaining from ex vivo infections confirmed that multiple types of pancreatic islet cells were susceptible to SARS-CoV-2, eliciting a cellular stress response and the induction of chemokines. Upon SARS-CoV-2 infection, beta cells showed a lower expression of insulin and a higher expression of alpha and acinar cell markers, including glucagon and trypsin1, respectively, suggesting cellular transdifferentiation. Trajectory analysis indicated that SARS-CoV-2 induced eIF2-pathway-mediated beta cell transdifferentiation, a phenotype that could be reversed with trans-integrated stress response inhibitor (trans-ISRIB). Altogether, this study demonstrates an example of SARS-CoV-2 infection causing cell fate change, which provides further insight into the pathomechanisms of COVID-19.”

ALSO SEE: COVID: Insulin Reduction, Diabetes, High Cholesterol, Heart Disease and Stroke

Increased Risk of Cancer
In the case of cancer and tumor suppression, COVID chooses people that have reduced P53 (the tumor suppression gene.) It is also possible that COVID further reduces functional P53 genes. “Mutations in p53 are found in most tumor types, and so contribute to the complex network of molecular events leading to tumor formation.” — The p53 tumor suppressor protein

COVID also suppresses NK cells. “A type of immune cell that has granules (small particles) with enzymes that can kill tumor cells or cells infected with a virus. A natural killer cell is a type of white blood cell. Also called NK cell and NK-LGL.” — Natural Killer Cell

A study “Cancer Prevention with Resistant Starch” (conducted over the last 30 years) shows that resistant starch reduces your risk of cancer. The resistant starches produce good bacteria that reduces a type of acid that promotes changes to your DNA. The changes to your DNA increase the risk of many types of cancer. The discovery may also explain in part why COVID increases your risk of cancer. COVID is known to destroy good gut bacteria.

Permanent Organ Damage

“Dr Betty Raman, from the University of Oxford and one of the lead investigators on the study, says it is clear that those living with long-COVID symptoms are more likely to have experienced some organ damage.”

The biggest impact was seen on the lungs, where MRI scans were 14 times more likely to show abnormalities. Scans were also three times more likely to show abnormalities in the brain, and twice as likely in the kidneys, among people who had severe COVID.

The article Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study was published September 22, 2023 in The Lancet Respiratory Medicine.

After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification.

ABOUT LONG-COVID
Long-standing multiorgan impairment following SARS-CoV-2 infection has been a major concern for individuals recovering from severe disease and is thought to be caused by a multitude of factors, including direct viral cytotoxicity, chronic inflammation, ischaemic injury, acute reactivation of other viruses, metabolic derangements, and acute treatment effects (especially invasive ventilation). Numerous reports of delayed organ complications such as myocarditis, stroke, and pulmonary emboli have led to speculations that the multiorgan dysfunction caused by COVID-19 might be responsible for impaired recovery and ongoing symptoms in individuals, a condition referred to as long COVID.

 

Long COVID Update:3 Years of Living With It

COVID-19 Chronic Conditions

COVID in Your Genes

MORE ON COVID: COVID-19 / SARS-CoV-2 / Novel Coronavirus

bookmark_borderCOVID-19: Immunity, Antibodies, Memory T Cells and B Cells

by Daniel Brouse
email: help@membrane.com

Omicron Update January 4, 2022

The effects of antibodies produced by the immune system’s “memory B cells” against the Omicron variant of the coronavirus are weakened. After the body learns to recognize SARS-CoV-2, B cells generate fresh antibodies against the virus if there are not enough antibodies circulating in the blood.

“Omicron seemed to evade a very large share of the memory B cells,” said Matthieu Mahevas and Pascal Chappert of Universite de Paris.

The research was published in Immune escape of SARS-CoV-2 Omicron variant from mRNA vaccination-elicited RBD-specific memory B cells. “Memory B cells (MBCs) represent a second layer of immune protection against SARS-CoV-2. Whether MBCs elicited by mRNA vaccines can recognize the Omicron variant is of major concern. We used bio-layer interferometry to assess the affinity against the receptor-binding-domain (RBD) of Omicron spike of 313 naturally expressed monoclonal IgG that were previously tested for affinity and neutralization against VOC prior to Omicron. We report here that Omicron evades recognition from a larger fraction of these antibodies than any of the previous VOCs. Additionally, whereas 30% of these antibodies retained high affinity against Omicron-RBD, our analysis suggest that Omicron specifically evades antibodies displaying potent neutralizing activity against the D614G and Beta variant viruses. Further studies are warranted to understand the consequences of a lower memory B cell potency on the overall protection associated with current vaccines.”

Updated August 4, 2021

COVID-19 Delta Variant and Vaccines
The efficacy of mRna vaccines is about 79% against contracting the Delta variant. Non-mRna vaccines are between 40-60% effective against Delta. Vaccines lose efficacy at about 3%/month after six months of being fully vaccinated. Vaccines appear to help contain the Delta variant to the nasal passage — you are less likely to develop the epigenetic changes to your genes (long-COVID).

We know the epigenetic changes caused by COVID partially dismantle your immune system including dysfunction of NAD+ optimization and suppression of T and NK cells.

There is no natural immunity from previous infection. Everybody needs to get vaccinated.

COVID Vaccine Breakthrough Cases
Q: Why are there so many breakthrough cases of COVID in the vaccinated?

A: There are several reasons why there are breakthrough cases with any vaccine; however, COVID is different. Many of the vaccinated people getting COVID already had COVID prior to being vaccinated. This is the second time they have contracted the virus. Once you have had COVID, your immune system is compromised. You should consider yourself immune compromised. The vaccine will not fully compensate for that fact.

THE ORIGINAL COVID STRAIN
A study published in The Lancet entitled Dynamics of SARS-CoV-2 neutralising antibody responses and duration of immunity: a longitudinal study found the immunity from a COVID reinfection varies widely from individual to individual from days to decades.

“We identified five distinctive patterns of neutralising antibody dynamics as follows:
* negative, individuals who did not, at our intervals of sampling, develop neutralising antibodies at the 30% inhibition level [12%];
* rapid waning, individuals who had varying levels of neutralising antibodies from around 20 days after symptom onset, but seroreverted in less than 180 days [27%];
* slow waning, individuals who remained neutralising antibody-positive at 180 days post-symptom onset [29%];
* persistent, although with varying peak neutralising antibody levels, these individuals had minimal neutralising antibody decay [32%];
* and delayed response, a small group that showed an unexpected increase of neutralising antibodies during late convalescence (at 90 or 180 days after symptom onset [2%]).

Persistence of neutralising antibodies was associated with disease severity and sustained level of pro-inflammatory cytokines, chemokines, and growth factors. By contrast, T-cell responses were similar among the different neutralising antibody dynamics groups. On the basis of the different decay dynamics, we established a prediction algorithm that revealed a wide range of neutralising antibody longevity, varying from around 40 days to many decades.

The question may also apply to vaccines: will the COVID immunity offered by vaccinations last for 40 days to many decades? What is the durability of vaccines and will it be uniform or vary widely from person to person?

Previously released on January 24, 2021:
1) Natural Immunity
If you get a moderate to severe case of COVID-19, most people maintain viable antibodies for 90 days and memory T-cells for 5 months. This will likely give you natural immunity to the same strain of COVID for up to 5 months. The resistance to the UK variant is thought to be diminished. The resistance to the South African variant is thought to be none. There is some concern that COVID may erase all or part of your T cells’ memory for other pathogens.

2) Vaccines
You should anticipate that vaccines will give you a very similar immune response as the natural immunity acquired from contracting COVID. It doesn’t matter which vaccine you receive. You should get whatever vaccine you can get and as soon as possible. You should anticipate needing to get vaccinated every 90 days once vaccines are developed for all the different variants.

The message is — we have to stop the community spread and the exponential rise in variants WORLDWIDE. Individual countries can not obtain herd immunity.

More Information on COVID-19



What We Use to Know about Immunity
Q: What do we know about immunity to COVID-19, the immune system, antibodies, memory T cells, and autoimmune disfunctions?
A: Not much. Today is September 2, 2020. The virus is still new. We probably won’t be able to know the longterm affects of COVID-19 until the longterm; however, there is a growing body of research that is starting to uncover some of the mysteries.

Q: Do we know if recovered COVID-19 patients have immunity to reinfection.
A: No. We do not know the durability of the antibodies, nor the length of memory of the T cells. Originally, researchers thought you could only catch COVID-19 once, and you would gain immunity. Scientists started off thinking you would have a minimum of 1 year immunity and quite possibly 2-3 years. Now, 6 months later, that theory is history.

There are several cases globally where reinfection was confirmed by identifying that the second infection was by a different mutation of COVID than the original infection. “So far, there are three patients known to have been infected with SARS-CoV-2 twice, and in at least one case the second time around was asymptomatic.”(1) Reinfection is rare, researchers said, but people should still be cautious. “If you’ve had it, you can’t necessarily be considered invulnerable to the infection,” Mark Pandori, one of the authors and director of the Nevada State Public Health Laboratory said.(2)

An extensive case study was conducted on the reinfection case from Nevada”
“These findings suggest that the patient was infected by SARS-CoV-2 on two separate occasions by a genetically distinct virus. Thus, previous exposure to SARS-CoV-2 might not guarantee total immunity in all cases. All individuals, whether previously diagnosed with COVID-19 or not, should take identical precautions to avoid infection with SARS-CoV-2. The implications of reinfections could be relevant for vaccine development and application.”(3) Half of the those that became reinfected had more serious symptoms with the reinfection.

Since this paper was first published, a study done by the Imperial College of London found a 26% decline in antibodies over a three month period. The study all but eliminates the possibility of herd immunity. The study also indicates any post-COVID immunity is short lived and chances of being reinfected are large.(4)

Q: Why do so many recovered patients appear to be getting reinfected?
A: Most recovered individuals are not getting reinfected, rather their immune system mistakes inactive strands of COVID RNA as active virus. The autoimmune system reacts with an autoimmune disconnect resulting in cycles of recurring symptoms.(5) In the short term, it is thought the recurring symptoms will not cause irreparable damage. The long haul for long haulers is less certain with the duration of your body attacking your own organs in question.

Q: How long do COVID antibodies last?
A: Again, we do not know. Originally, it was thought the antibodies would last for a long period and the memory T cells might give you lifelong immunity. That is no longer the science. “There is currently no evidence that people who have recovered from COVID-19 are protected from a second infection.”(6) A study published in the New England Journal of Medicine, found that antibody levels against the novel coronavirus decreased by about half every 73 days and, if that rate were sustained, would be depleted within about a year. The findings are similar to those of several previous reports showing rapidly decreasing antibody levels after infection, including one published Jun 18 in Nature, which showed that levels of antibodies against COVID-19 began to decrease within 2 or 3 months of infection.(7)

Q: What immunity do T Cells give?
A: We don’t know. There are two types of T Cells. Memory T cells live for six months or less in healthy humans (Westera et al., 2013), whereas naive T cells can live for up to nine years (Vrisekoop et al., 2008). Memory T cells are the ones that remember your previous infections and how to fight them. Memory T cells reproduce passing on their memory. There is growing concern that the memory T cells may be forgetting. It is possible that COVID erases the memory of your T cells making you susceptible to get infected by any other disease or illness you have previous had or have been vaccinated for (as measles can do.) Measles seem to wipe out immune cells that ‘remember’ encounters with specific bacteria and viruses.(8)

RECOMMENDATION:
Until more is known, recovered COVID patients should take great care and avoid exposure to all bacteria and viruses, including COVID, that may cause illness.

1. Patients Reinfected with Coronavirus in Hong Kong, Europe (The Scientist)
2. 1st U.S. COVID-19 Reinfection Reported in Nevada Patient (WebMD / NBC)
3. Genomic evidence for reinfection with SARS-CoV-2: a case study (The Lancet)
4. Declining prevalence of antibody positivity to SARS-CoV-2: a community study of 365,000 adults Imperial College London
5. COVID-19 Long Haulers: autoimmune response due to inactive particles of the virus (Daniel Brouse)
6. “Immunity passports” in the context of COVID-19 (WHO)
7. COVID-19 antibodies decay quickly after mild illness (Center for Infectious Disease Research and Policy)
8. Measles erases immune ‘memory’ for other diseases (Nature)

COVID-19 Index