COVID VACCINES, LONG COVID and SPIKE PROTEIN by Nika Cristiani
This is a developing blog based on research by Nika Cristiani and scientific studies as we learn more. Beginning of Nika's research : August 2022, with studies going back to 2021.
My name is NIKA Cristiani , Co-founder of GYM IN A BOX ® NextGen StimFitTech. I am also a certified nutritionist and renowned wellness and fitness technology professional with over 30 years of experience. My commitment to the health and well-being of my clients and customers motivated me to research Long Covid, the vaccines, and the rise of Spike Protein levels in patients, beginning in August 2022. I am a passionate advocate for vaccination and strongly encourage everyone to receive the Covid vaccine, unless they have allergies or underlying conditions that contraindicate it.
Recent studies have demonstrated that, first, vaccines lower the risk of severe acute infections, which are associated with an increased risk of Long COVID. Additionally, vaccines enhance the immune system's ability to eliminate the virus more rapidly, minimizing the chances that residual viral particles remain in the body.
Is there anything that helps long COVID symptoms?
Physical therapy & fitness. Physical therapy incorporates exercise, massage and other treatments that can help you with pain or movement issues. Pulmonary rehabilitation. Pulmonary rehabilitation is a special kind of exercise and education program that can help you breathe better and learn how to manage breathing issues at home. Youn may use all of our GYM IN A BOX StimFit Massager devices.
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I hope my research contributes to improving the health of many individuals. Thanks to scientific advancements and the work of remarkable scientists around the globe, we are making significant and rapid progress in our understanding of these issues.
Most recent Source 2024: Yale Medicine https://www.yalemedicine.org/news/covid-vaccines-reduce-long-covid-risk-new-study-shows#:~:text=First%2C%20vaccines%20reduce%20the%20risk,viral%20particles%20are%20left%20behind
For their study, Dr. Al-Aly’s team utilized databases within the VA to identify nearly 450,000 veterans who had been infected with SARS-CoV-2, as well as healthy controls. They divided this cohort into era-specific groups based on the SARS-CoV-2 variant: pre-Delta era (no vaccination), Delta era (no vaccination), Delta era (vaccinated), Omicron era (no vaccination), and Omicron era (vaccinated). They followed each group for a year to identify which one was most at risk for developing Long COVID symptoms. The researchers found that the rate of new Long COVID cases declined with each variant, and that the numbers of cases were significantly lower in the vaccinated cohorts.
Then, the team conducted analyses to uncover the reasons for the observed decline in Long COVID cases from the pre-Delta to Omicron eras. About 70% of the decline was attributable to vaccination, they found.
There are several reasons to explain why vaccines may prevent Long COVID, says Dr. Al-Aly. First, vaccines reduce the risk of severe acute infections, which are linked to a greater risk of Long COVID. Vaccines also help the body’s immune system to eliminate the virus more quickly, reducing the likelihood that lingering viral particles are left behind.
Viral persistence is one of researchers’ multiple hypotheses for the drivers of Long COVID. “That really means that maintaining vaccination uptake is likely to be an important driver to keep the lid on Long COVID,” Dr. Al-Aly says.
The other 30% was related to changes in viral characteristics. In other words, as SARS-CoV-2 evolved, it changed in ways that may have made people less susceptible to developing Long COVID.
Interestingly, while the overall risk of Long COVID has declined, the researchers found that unvaccinated individuals now face a greater chance of developing metabolic and gastrointestinal disorders, including diabetes and dyslipidemia (abnormal levels of fat in blood), post-COVID compared to earlier groups. “We have a large cohort of people with metabolic disorders in the United States who may be at particular risk of those being exacerbated with COVID,” says Dr. Roberts. “This needs to be looked at in greater detail.”
How will Long COVID risk continue to evolve?
Long COVID afflicts 400 million people around the world, and experts estimate that the disease has an economic impact as high as $1 trillion each year, according to a recent review including Dr. Al-Aly and Akiko Iwasaki, PhD, Sterling Professor of Immunobiology. The latest study inspires the question—will SARS-CoV-2 continue to evolve so that one day the risk of Long COVID might become negligible? Experts still don’t know, says Dr. Al-Aly. “Theoretically, it’s possible, but from what we’ve seen so far, I doubt it.”
The risk of Long COVID is not static, the findings show. It could continue to decline or might potentially bounce back if more people choose to forgo vaccination. Scientists will need to continue to monitor SARS-CoV-2 and how it evolves to understand how Long COVID risk patterns change with it. Dr. Al-Aly’s team plans to conduct long-term studies and characterize the effects of Long COVID on various organ systems. In the meantime, keeping up with vaccinations will be very important for reducing your personal risk, he says.
“If Long COVID was a kid, it would be in kindergarten,” he says. “It’s very young and very new, and there’s a lot to learn.”
Isabella Backman is associate editor and writer at Yale School of Medicine
How NIKA’s research started:
Study from Jan 14, 2021
Domains and Functions of Spike Protein in SARS-Cov-2 in the context of Vaccine Design
https://pmc.ncbi.nlm.nih.gov/articles/PMC7829931/
Study from July 25, 2022 :
Coronavirus spike protein activated natural immune response, damaged heart muscle cells
A few months later, according to available data, by 30 September 2022, 68% of the world’s population had received at least one dose of the COVID-19 vaccine, and 12.74 billion doses had been administered . The vaccines most commonly administered were Comirnaty (Pfizer/BioNTech), Covishield (Astrazeneca), CoronaVac (Sinovac), Spikevax (Moderna), and Jcovden (Johnson & Johnson). Of these, approximately 30% of the doses produced by 22 January 2022 were in the form of a novel vaccine with a synthetic N1-methyl-pseudoiridinylated mRNA encapsulated in a lipid nanoparticle (LNP) .
LNPs are a new technology that was not used in vaccine delivery until the emergency use authorization (EUA) of the Pfizer/BioNTech BNT162b2 and Moderna mRNA-1273 COVID-19 vaccines . This was also unprecedented in the approval process, being the fastest for any vaccine , leaving many concerns with regard to long-term safety , which was difficult to evaluate due to the unblinding of the initial clinical trials .
Whilst the delivery technology of LNPs have previously been used to deliver small molecules, it has only recently been used to deliver RNA. LNPs are advantageous for targeting brain tissue, as they can cross the blood–brain barrier (BBB) . The first drug used and LNP to deliver RNA was a small interfering RNA (siRNA)-based drug, known as Onpattro (Alnylam Pharmaceuticals), first approved in 2018 for the treatment of polyneuropathies .
Given both the novelty of the technology and the paucity of data on which approval was based (which was also subject to data integrity issues , long-term effects cannot be definitively ruled out, especially because many of the foundational claims on which approval was based have been contested by recent experiments . For example, in contrast to claims that the injection stayed at the injection site, and that spike protein would only be expressed for a short period of time (based on the lability of non-pseudouridylated RNA, the contents and products of the COVID-19 vaccines have been found in the blood stream of most vaccinees studied within hours to days.
Long COVID-19 patients (post SARS-CoV-2 infection) show spike protein persistence up to 15 months . Another study showed spike protein persistence in the gut of long COVID-19 patients, but not in the bloodstream.
Spike proteins can be packaged in exosomes , possibly resulting in inflammation and immune activation in organs and tissues distant from the injection site . Extracellular vesicles are capable of crossing the blood–brain barrier, and LNPs, as well as exosomes, will exchange more readily in small diameter vessels with low flow rates (i.e., capillaries and small vessels). Importantly, the spike protein seems to additionally impact blood–brain barrier permeability . These results challenge the initial mechanistic foundation on which the presumption of safety is contingent.
Methods
This review begins by summarizing the mechanisms of harm from spike protein, either from COVID-19 illness or form COVID-19 vaccination. We also cover the clinical aspects, which can affect the course of the disease. The review then moves to therapeutic mechanisms, which can address the spike protein via different pathways.
The spike protein on the SARS-CoV-2 virus binds to cells in the human body, allowing the virus to replicate.
Several hypotheses for the mechanisms of long COVID-19 exist, including immune dysregulation, auto-immunity, endothelial dysfunction, activation of coagulation, and latent viral persistence , though this review focuses on the elements common to both COVID-19 infection and vaccine injury. Cardiovascular complications, particularly microthrombus formation, feature both in the etiologies of long COVID-19 as well as COVID-19 vaccine injury.
The SARS-CoV-2 (infection or vaccine produced) spike protein can bind to the ACE2 receptor on platelets, leading to their activation , and it can cause fibrinogen-resistant blood clots .
Ontologically, both infection and vaccination express the spike protein, though some subtle differences exist between the vaccine-generated and the infection-generated spike protein. Importantly, the spike protein encoded by vaccines is static and does not undergo evolution, whereas the spike protein produced by infection evolves as the virus evolves .
In 2021, a comprehensive investigation revealed consistent pathophysiological alterations after vaccination with COVID-19 vaccines, including alterations of immune cell gene expression.
Clinical Observations
Although no official definition exists for ‘post-COVID-19-Vaccine Syndrome,’ a temporal correlation between receiving a COVID-19 vaccine and the beginning or worsening of a patient’s clinical manifestations is sufficient to make the diagnosis of a COVID-19 vaccine-induced injury when the symptoms are unexplained by other concurrent causes. It should, however, be recognized that there is a significant overlap between the symptoms and features of the long COVID-19 syndrome and the post-COVID-19-Vaccine Syndrome . However, a number of clinical features appear to be distinctive of the post-COVID-19 vaccine syndrome; most notably, severe neurological symptoms (particularly small fiber neuropathy) appears to be more common following vaccination . To complicate matters further, patients with long COVID-19 are often vaccinated , making the issue of definition more difficult.
Unfortunately, only post mortem examination to date can prove causal relationship when tissues damaged demonstrate the presence of spike protein and absence of nucleocapsid protein (SARS-CoV-2 only) .
The true magnitude of post-COVID-19-Vaccine Syndrome is unknown, as data are limited to short duration clinical trials. From a survey of vaccinated individuals, approximately 1% required medical attention immediately following vaccination . A nationwide cohort study of U.S. veterans reported adverse reactions in 8.5% of recipients of the Pfizer vaccine and 7.9% of those receiving the Moderna vaccine .
A number of factors are associated with an increased risk of adverse events; these include:
- Genetics: first-degree relatives of people who have suffered a vaccine injury appear to be at a very high risk of vaccine injury. People with a methylenetetrahydrofolate reductase (MTHFR) gene mutation and those with Ehlers-Danlos type syndromes, may be at an increased risk of injury. Increased homocysteine levels have been linked to worse outcomes in patients with COVID-19 . Increased homocysteine levels may potentiate the microvascular injury and thrombotic complications associated with spike protein-related vaccine injury .
- mRNA load and quantity of spike protein produced: this may be linked to specific vaccine lots that contain a higher concentration of mRNA due to variances in manufacturing quality, as well as heterogeneity within the vial .
- Type and batch of vaccine: variances in the levels of adverse reactions were observed, depending on the manufacturer of the vaccine .
- Number of vaccines given: the risk of antibody enhancement (ADE) increases with each exposure to the virus or a vaccine. A negative inverse correlation of dosages given, as well as effectiveness, was also observed .
- Sex: the majority of vaccine-injured people are female, and vaccines historically have sex-specific effects .
- Underlying nutritional status and comorbidities: certain preexisting conditions may likely have primed the immune system to be more reactive after vaccination . This includes those with preexisting autoimmune disorders .
Given the intricate influence of gut microbiota (GM) on host immune effectors and subsequent inflammatory profile, GM composition and function might contribute to explaining the individual resilience/fragility with respect to COVID-19 and/or the response to therapeutics (vaccines), which deserve further research. Microbial diversity can be improved by consuming many prebiotics and probiotics, such as sauerkraut and kimchi.
The design and discovery of spike protein inhibitors have followed a typical drug repurposing process. Given the structural similarity of the SARS-CoV-2 spike protein to other coronaviruses , compounds that work for these could potentially be repurposed for SARS-CoV-2 spike inhibition.
Given the many uncertainties around the duration of spike protein production and the variables determining production, adopting a preventive approach seems sensible, provided the proposed interventions are safe. It remains unknown whether full recovery from COVID-19 Vaccine Injury is possible. However, we suggest targeting several different processes to reduce symptoms associated with both vaccine injury and long COVID-19. These include:
- (1) Establishing a healthy microbiome
- (2) Inhibiting spike protein cleavage and binding (stopping ongoing damage)
- (3) Clearing the spike protein from the body (clearing the damaging agents)
- (4) Healing the damage caused by the spike protein (restoring homeostasis and boosting the immune system)
https://pmc.ncbi.nlm.nih.gov/articles/PMC10010667/
May 17,2023
Compounds which bind to the ACE2 receptor can also antagonistically compete with the spike protein for a limited number of receptor sites. For example, the diabetes medication metformin has been identified as a potential long COVID-19 therapeutic agent due to this mechanism of action.
How to remove spike proteins from the body?
Clearing of spike proteins can also be accomplished by increasing autophagy, which clears proteins and recycles their amino acids
The novel coronavirus’ spike protein plays additional key role in illness
Salk researchers and collaborators show how the protein damages cells, confirming COVID-19 as a primarily vascular disease
LA JOLLA—Scientists have known for a while that SARS-CoV-2’s distinctive “spike” proteins help the virus infect its host by latching on to healthy cells. Now, a major new study shows that the virus spike proteins (which behave very differently than those safely encoded by vaccines) also play a key role in the disease itself.
The paper, published on April 30, 2021, in Circulation Research, also shows conclusively that COVID-19 is a vascular disease, demonstrating exactly how the SARS-CoV-2 virus damages and attacks the vascular system on a cellular level. The findings help explain COVID-19’s wide variety of seemingly unconnected complications, and could open the door for new research into more effective therapies.
COVID-19: New Research Shows How the Virus Enters Our Cells and May Lead to Better VaccinesVaccines
https://medicine.yale.edu/news-article/covid-19-new-research-shows-how-the-virus-enters-our-cells-may-lead-to-better-vaccines/
August 15, 2024
by Rachel Tompa, PhA study has captured new views of the intricate molecular dance between our cells and the COVID-19-causing virus, SARS-CoV-2—findings that could inform the development of more effective vaccines as additional variants emerge.
Published August 15 in the journal Science, the study reveals how SARS-CoV-2 uses its spike protein, pointy molecules that stud the virus’s outer surface, to grab onto and drag itself to touch the surface of human cells and eventually deliver its viral genomes into cells. The study was carried out by researchers at Yale School of Medicine (YSM), Northeastern University, and Rice University.
This is the first time we’ve seen the structure of the intermediate stages of the spike during fusion. We found that this region is even more dynamic than what we thought before. Wenwei Li, PhD
The virus’s attachment to cells via its spike protein is the first key step for the virus to fuse with and infect the cells. Current COVID-19 vaccines work by blocking the virus from attaching to cells; the new study shows details of how certain human antibodies can block the next step, virus-to-cell fusion. This is important, because as effective as the vaccines have been for millions of people, they could come up short against future SARS-CoV-2 variants due to the virus’s rapid mutation.
“Understanding how these antibodies work to block the fusion machine can help us understand how to better design immunogens [for better vaccines],” said Michael Grunst, the first author on the study and a doctoral student working in the lab of Walther Mothes, PhD, Paul B. Beeson Professor of Medicine at YSM.
A two-part viral spike
The viral spike protein is made of two parts: one that binds to the human protein ACE2, which sits on the surface of many kinds of human cells and is the virus’s portal for infection, and another part that changes its shape to move the virus closer to the human cell once it is attached. Bringing the virus and cell very close together is necessary for infection, as the membranes of the virus and the cell need to fuse for the virus to enter the cell.
COVID-19 vaccines now on the market were designed to include the ACE2-binding portion of the spike protein, which is prone to pick up mutations as the virus evolves. Even with yearly updates to the vaccine, COVID vaccine designers won’t be able to keep up with mutations that have occurred in this part of the protein. But a different potential target of opportunity — the shape-changing part of the protein — is very unlikely to mutate, because its structure is so critical for narrowing the gap between virus and cell.
The stable structure in that area suggests future vaccines that target it might be universally effective against more dangerous SARS-CoV-2 variants, and could even work against other coronaviruses, such as the viruses that cause Middle East Respiratory Syndrome (MERS) or the original Severe Acute Respiratory Syndrome (SARS), said Mothes. Antibodies against this region are effective against a wide variety of SARS-CoV-2 variants, including so-called variants of concern, which are newly evolved variants that may be more infectious or more transmissible than the original virus.
To simulate binding between the proteins that is close to real-life conditions, the Yale scientists used virus-like particles coated with either the spike protein or ACE2. They imaged the interaction between the two proteins using a microscopy technique known as cryogenic electron tomography, or cryo-ET, which captures detailed 3D structures of molecules. Their collaborators at Northeastern and Rice then used the imaging data gathered by the Yale team to build computational simulations of the entire process.
The cutting-edge imaging technique combined with the computer models allowed the team to take images of the spike-ACE2 interaction and the following fusion intermediates that had not been seen before with that level of detail. For example, they were able to see new details of the spike protein’s dramatic shape change—it looks somewhat like a jackknife folding shut, as Grunst described it.
“This is the first time we’ve seen the structure of the intermediate stages of the spike during fusion,” said Wenwei Li, PhD, associate research scientist in the Mothes Laboratory, who led the study along with Mothes and Paul Whitford, PhD, associate professor of physics at Northeastern. “We found that this region is even more dynamic than what we thought before.”
Imaging to inform vaccine design
They also captured images of the two proteins together with antibodies that bind to the shape-changing region of the spike protein. With the computer simulations, the team was able to show that the antibody blocks the spike protein from folding in on itself, preventing it from pulling the virus and cell membranes close enough to fuse.
They also found that antibodies bind to a transient folded form of the spike protein, perhaps explaining why these antibodies are naturally relatively rare—our immune systems only have a short window of time of exposure to this particular shape of the protein. The details about the shapes the spike protein undergoes as it folds could help vaccine developers pick the ideal part of the virus to stimulate the production of more of these antibodies, Mothes said.
“COVID variants can escape our immune systems and vaccines by mutating, but these fusion machines have only one pattern of how to do their job,” he said. “It’s a hardwired, conserved machine; you can’t change them. So this is why understanding more about how that mechanism works means we can learn more about their vulnerability, to [use vaccines to] block this process with antibodies.”
A new study found that a protein most commonly found in blood vessels and the brain may enhance COVID-19's ability to bind with cells.
When SARS-CoV-2 enters the human body, the virus’ spike protein binds to a cell, allowing the virus to infiltrate and begin replicating.
A new study from Tulane University, conducted in partnership with Florida International University and published in Protein Science, has identified a protein that may be the glue that helps COVID’s spike protein stick.
The study found that a small piece of a proteoglycan called perlecan LG3 – a protein most commonly found in blood vessels and the brain – readily formed a stable bond with the COVID spike protein and perhaps enhanced the virus’ ability to bind with cells.
Recent studies have identified proteoglycans as potential key factors in COVID infections. By identifying key interactions between perlecan LG3 and SARS-CoV-2, this study may open the door for new forms of treatment, said co-corresponding author Dr. Gregory Bix, director of Tulane University School of Medicine’s Clinical Neuroscience Research Center.
“The takeaway is this major extracellular matrix proteoglycan found in blood vessels throughout the body most likely plays a significant role in how the virus sticks to and infects cells,” said Bix, who has studied perlecan for 25 years as a treatment for cerebrovascular diseases such as stroke and dementia. “Perhaps this explains COVID’s impact on the vascular system and the brain, but LG3 seems to act as a sort of bridge for the virus.”
Using molecular modeling simulations, the study found that LG3 displayed a “high affinity stable interaction” with the COVID spike protein’s receptor-binding domain, the area that attaches to host cells. This attraction was confirmed using surface plasmon resonance instruments, which use electrons to measure interactions and affinity between molecules.
One prominent type of hydrogen bond found between the COVID spike protein and a host cell only appeared in the study when LG3 was present, suggesting that LG3 may enhance COVID’s ability to bind to a cell.
Further studies are needed to determine if these binding interactions can be affected by mutations in various strains of COVID.
Bix also hopes these findings can lead to new forms of COVID prevention or treatment.
“Can decoy pieces of perlecan prevent the virus from binding to cells? Can antibodies block this interaction between LG3 and the spike protein? There’s still so many theories and so much we don’t know,” Bix said. “Continuing to understand how the virus infects cells is critical, especially when you have an ever-evolving virus.”
https://news.tulane.edu/pr/study-protein-may-be-glue-helps-covid-virus-stick
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