Covid-19 News

Researchers Connect Spinal Fluid Autoantibodies to Neurological Symptoms in COVID-19 Patients

https://medicine.yale.edu/news-article/30370/

In March of 2020, Shelli Farhadian, MD, PhD, assistant professor of medicine (infectious diseases) and neurology, began to see parallels in her pre-pandemic research on neurologic effects in patients with HIV infection and the possibility of neurologic effects on patients with SARS-CoV-2, or COVID-19.

“There was some literature out there that suggested that coronaviruses could have an effect on the brain. So, knowing that that was a potential possibility, even before we had our first case at Yale New Haven Hospital, I worked with other people to set up a protocol where we could consent patients to collect tissue specimens and information to try to see if this was also going happen with SARS-CoV-2,” explained Farhadian.

The first COVID-19 positive patient was admitted to Yale New Haven Hospital (YNHH) on March 14, 2020. Farhadian and her infectious diseases colleagues encountered patients with neurological complaints with the absence of other traditional COVID-19 symptoms, who then later tested positive for the disease.

“Large cohort studies in China, France, and New York City, estimated that somewhere around 30% of hospitalized patients with COVID-19 have some sort of neurological component to their illness. So in that context and with our background in studying the neurological effects of systemic infections, we started to ask whether there was inflammation or some other consequence of this infection affecting the brain,” said Farhadian.

Patients enrolled in the study underwent a lumbar puncture to drain cerebral spinal fluid from their back, the same fluid that surrounds the brain. Farhadian and her collaborators across Yale School of Medicine and the University of California, San Francisco (UCSF), knew that by looking at the spinal fluid, they would learn what is going on within the brain.

“We took the spinal fluid to try to see if we can get a window into what was going on in the brain.,” said Farhadian.

The study, “Exploratory neuroimmune profiling identifies CNS-specific alterations in COVID-19 patients with neurological involvement,” currently in preprint on bioRxiv found that unique immune responses were seen in the spinal fluid compared to what was going on in the rest of the body, including increased levels of antibody producing cells than would typically be expected in the spinal fluid. They also found a high level of autoantibodies in the spinal fluid, which suggests that these brain-targeting antibodies are a potential contributor for the neurological complications.

“We found that most of the patients we studied had autoantibodies, or antibodies that target brain tissue, circulating in the spinal fluid. In one case, we found that antibodies that are directed against the virus were also cross-reacting against the brain. We think this might prove to be a link between the virus and the high rates of neurological symptoms that people show during and after COVID-19.” Now, Farhadian and Yale neurologists Dr. Serena Spudich and Dr. Lindsay McAlpine are seeing patients in the Yale Post-COVID neurology clinic who are two to six months out from their COVID diagnosis, and are still having neurological problems. “For example, I saw one a patient last week who is normally a vivacious and active woman, but after her COVID illness, is unable to work. She says she cannot think straight, gets lost easily, and can't do simple tasks like grocery shopping. Are those auto-antibodies contributing to that? That's something that we need to get to the bottom of,” said Farhadian.

The researchers are actively enrolling patients with post-COVID neurological problems in their study. For more information on the COVID Mind Study at Yale, visit their website.

Farhadian commended the collaboration in this work, like UCSF neurologists Michael Wilson, MD, Samuel Pleasure, MD, PhD, and Christopher Bartley, MD, PhD, along with many colleagues at YSM, such as Eric Song, an MD/PhD student in the Iwasaki Lab.

“My UCSF partners, Michael Wilson and Sam Pleasure, are leaders in their field. I knew of them, but hadn’t worked with them before. We connected early on in the pandemic and were able to combine my background and interest in neuro-infectious disease with their expertise in auto-immunity, to bring this project together. Here at Yale, I was delighted to collaborate with Eric Song and Akiko Iwasaki in Immunobiology. Eric had been working to develop mouse models of SARS-CoV-2 infection, including mice that specifically had brain infection. It was good opportunity to study the similar phenomenon that we were seeing in our patients in that animal model.”

Cheap, potent pathway to pandemic therapeutics

https://www.eurekalert.org/pub…2021-02/uop-cpp021121.php

PITTSBURGH, Feb. 15, 2021 - By capitalizing on a convergence of chemical, biological and artificial intelligence advances, University of Pittsburgh School of Medicine scientists have developed an unusually fast and efficient method for discovering tiny antibody fragments with big potential for development into therapeutics against deadly diseases.

The technique, published today in the journal Cell Systems, is the same process the Pitt team used to extract tiny SARS-CoV-2 antibody fragments from llamas, which could become an inhalable COVID-19 treatment for humans. This approach has the potential to quickly identify multiple potent nanobodies that target different parts of a pathogen--thwarting variants.

"Most of the vaccines and treatments against SARS-CoV-2 target the spike protein, but if that part of the virus mutates, which we know it is, those vaccines and treatments may be less effective," said senior author Yi Shi, Ph.D., assistant professor of cell biology at Pitt. "Our approach is an efficient way to develop therapeutic cocktails consisting of multiple nanobodies that can launch a multipronged attack to neutralize the pathogen."

Shi and his team specialize in finding nanobodies--which are small, highly specific fragments of antibodies produced by llamas and other camelids. Nanobodies are particularly attractive for development into therapeutics because they are easy to produce and bioengineer. In addition, they feature high stability and solubility, and can be aerosolized and inhaled, rather than administered through intravenous infusion, like traditional antibodies.

By immunizing a llama with a piece of a pathogen, the animal's immune system produces a plethora of mature nanobodies in about two months. Then it's a matter of teasing out which nanobodies are best at neutralizing the pathogen--and most promising for development into therapies for humans.

That's where Shi's "high-throughput proteomics strategy" comes into play.

"Using this new technique, in a matter of days we're typically able to identify tens of thousands of distinct, highly potent nanobodies from the immunized llama serum and survey them for certain characteristics, such as where they bind to the pathogen," Shi said. "Prior to this approach, it has been extremely challenging to identify high-affinity nanobodies."

After drawing a llama blood sample rich in mature nanobodies, the researchers isolate those nanobodies that bind specifically to the target of interest on the pathogen. The nanobodies are then broken down to release small "fingerprint" peptides that are unique to each nanobody. These fingerprint peptides are placed into a mass spectrometer, which is a machine that measures their mass. By knowing their mass, the scientists can figure out their amino acid sequence--the protein building blocks that determine the nanobody's structure. Then, from the amino acids, the researchers can work backward to DNA--the directions for building more nanobodies.

Simultaneously, the amino acid sequence is uploaded to a computer outfitted with artificial intelligence software. By rapidly sifting through mountains of data, the program "learns" which nanobodies bind the tightest to the pathogen and where on the pathogen they bind. In the case of most of the currently available COVID-19 therapeutics, this is the spike protein, but recently it has become clear that some sites on the spike are prone to mutations that change its shape and allow for antibody "escape." Shi's approach can select for binding sites on the spike that are evolutionarily stable, and therefore less likely to allow new variants to slip past.

Finally, the directions for building the most potent and diverse nanobodies can then be fed into vats of bacterial cells, which act as mini factories, churning out orders of magnitude more nanobodies compared to the human cells required to produce traditional antibodies. Bacterial cells double in 10 minutes, effectively doubling the nanobodies with them, whereas human cells take 24 hours to do the same.

"This drastically reduces the cost of producing these therapeutics," said Shi.

Shi and his team believe their technology could be beneficial for more than just developing therapeutics against COVID-19--or even the next pandemic.

"The possible uses of highly potent and specific nanobodies that can be identified quickly and inexpensively are tremendous," said Shi. "We're exploring their use in treating cancer and neurodegenerative diseases. Our technique could even be used in personalized medicine, developing specific treatments for mutated superbugs for which every other antibiotic has failed."

Quote from Navid

This is witchcraft. They are saying that they believe scientifically the vaccine reduced the severity of the illness. That is one of the most garbage unscientific statements I've ever heard.

No, it is common knowledge. True of many vaccines, going back to Jenner. Reduced severity was reported for the double blind tests of both vaccines, and in Israel and the UK.

Quote from Fm1

In speaking with Contagion® on the matter of the new ChAdOx1 findings, expert vaccinologists stressed the utility of the vaccine in reducing severe COVID-19 disease and hospitalizations. That said, they estimated alteration to the vaccine to appropriate respond to the South Africa variant would take another 6 months, and in the meantime, mRNA platform-based vaccines may be more suitable to respond to more transmissible variants than adenovirus-based vector platforms including ChAdOx1 and Ad26.COV2.S

Reports say the mRNA vaccines can be adjusted for the South Africa variant quickly. Within weeks if necessary. Researchers are discussing a plan to give the first set of patients a third shot (a second booster) for the South Africa variant, if that is needed, after everyone gets the first two. I think this is the plan:

1. People now get shots 1 and 2. They are group 1.

2. The vaccine is reprogrammed to fit the South Africa variant. It still works for earlier forms.

3. The people who were not vaccinated in step 1 get reprogrammed shots 1 and 2. They are safe from the South Africa variant. They are group 2.

4. After everyone is vaccinated, people in group 1 get a third vaccine; the booster developed in step 2. A mopping-up up operation, if you will.

As noted, the J&J vaccine cannot be reprogrammed as quickly, and it may not protect against some of the newer variants. It is also not as effective. So it might also need a booster. For now, though, it would be tremendous help getting most of the population covered quickly. I think if you stop the most common form of the virus, you reduce the likelihood of additional dangerous variants emerging.

Quote from Alan Smith

Navid.

So, the pool of fully vaccinated citizens the report covers 677,000 people, and the reinfections total 4 cases. A percentage so small I cannot be arsed to calculate it. Even if it were 4,000 it would represent only a tiny fraction of the vaccinated population.

When you consider that (for example) chronic alcohol abuse and extreme obesity are both factors which negate the immune response to vaccines, I think that this is a great example of useful science at work,

If people are getting serous immune reactions or even dying from the vaccine, due to immune stimulation, or antibody dependent enhancement, or pathogenic priming, then saying the vaccine works is contra-reality.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7142689/

Reality could be, and looks to be imo, 180 degrees. The vaccine just may cause the thing you say you are preventing in the very population who are at risk...but what's worse the pathogenic priming could happen to everyone.

Because of the above, saying the vaccine 'lowers the burden of disease' is rather interesting. I am quite sure if you look at the VAERS database this is likely already proving out.

Quote from Navid

If people are getting serous immune reactions or even dying from the vaccine, due to immune stimulation, or antibody dependent enhancement, or pathogenic priming, then saying the vaccine works is contra-reality.

Since none of that is happening, it isn't a problem, is it? Imaginary problems are not real problems.

Quote from RobertBryant

Unfortunately not all doctors can read.

Dr. Ebony Hilton." These (ivermectin) trials exclude lots of people ... one of which is me.. I.'m a woman"

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""Dr. Ebony Hilton shares that we should make sure that this drug is truly safe to treat everyone".

So tell me, Dr. Ebony Hilton, your opinion on injecting people with vaccines

that are barely tested and of which nobody knows the consequences in the long term. Please, enlighten me!

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What contract did these people sign that they can't sign on to straightforward science about a well known drug with benefit to risk ratio through the roof!

And you know Dr. Hilton would be talking about "vaccine equality" and "racial justice with vaccines" and "vaccine nationalism" --- who's pulling their strings?

Quote from JedRothwell

Reports say the mRNA vaccines can be adjusted for the South Africa variant quickly. Within weeks if necessary. Researchers are discussing a plan to give the first set of patients a third shot (a second booster) for the South Africa variant, if that is needed, after everyone gets the first two. I think this is the plan:

1. People now get shots 1 and 2. They are group 1.

2. The vaccine is reprogrammed to fit the South Africa variant. It still works for earlier forms.

3. The people who were not vaccinated in step 1 get reprogrammed shots 1 and 2. They are safe from the South Africa variant. They are group 2.

4. After everyone is vaccinated, people in group 1 get a third vaccine; the booster developed in step 2. A mopping-up up operation, if you will.

As noted, the J&J vaccine cannot be reprogrammed as quickly, and it may not protect against some of the newer variants. It is also not as effective. So it might also need a booster. For now, though, it would be tremendous help getting most of the population covered quickly. I think if you stop the most common form of the virus, you reduce the likelihood of additional dangerous variants emerging.

Display More

I keep hearing that these vaccines can be adjusted but how many adjustments can be made to a vaccine that targets the spike protein? This could potentially create a vaccine resistant virus, more mutations to the original strain are happening all over the world, a boatload was discovered in california just this past week.

Quote from Fm1

I keep hearing that these vaccines can be adjusted but how many adjustments can be made to a vaccine that targets the spike protein? This could potentially create a vaccine resistant virus, more mutations to the original strain are happening all over the world, a boatload was discovered in california just this past week.

This is "the plan." Having people walk around with partial antibody responses is the best way to make new strains! EVERYBODY knows it. The Paul Offit's of the world just say - thats fine we'll deal with this later!

U.S. cases are declining rapidly. This is the third decline, and by far the largest and most rapid. The other two were in July 2020 and Dec. 18, 2020. Experts say all three declines were caused by the same factors: increased use of masks, social distancing and lockdowns. They also say some natural seasonal decline may be taking place. See:

https://www.cnn.com/2021/02/14…navirus-sunday/index.html

https://www.worldometers.info/coronavirus/country/us/

One expert (in an article I cannot find) said the vaccines are not yet playing a large role in the decline. Japan is also experiencing a rapid decline. That cannot be caused by the vaccines, because vaccinations will not begin there until tomorrow. Reports say the decline in Japan is due to partial lockdowns, masks, and case tracking, which faltered for a while when the numbers were higher.

https://www.worldometers.info/coronavirus/country/japan/

There is no doubt that vaccines are playing a major role in the decline in Israel.

This is mere speculation by me, but I think the vaccinations may be affecting the U.S. numbers more than you might expect. First, because there may be the beginning of herd immunity. Second, because vaccines may not be reducing cases as much as they are changing the number of reported cases. Here is what I suppose:

In the U.S., 8.5% of the population has been "officially" infected. Those are people who thought they were sick, and were tested to confirm that. Many more people probably got sick but never went to the doctor or got tested. Estimate vary. It might be 18 to 30% of the entire population. Add to that the 12% that has now been vaccinated and ~40% of the population is immune. That is enough to show the first signs of herd immunity. The curve should flattening. You can see that in computer simulations.

Many young people have had mild cases and were never tested. I know several like that. Older people who are infected tend to have more serious cases, or they are frightened because the disease is more dangerous for them, so they go to the doctor and get tested. So, the official numbers are probably slanted toward older patients. They are counted more often. Here's the thing: Most vaccines have been given to the older population. 12% of the whole population has been vaccinated, but it is ~25% of old people, who are part of the "prioritized" population. (The vaccinated elderly population ranges from 10% to 34% in different states. See Fig. 4: https://www.kff.org/coronaviru…s-supply-remains-limited/) So, I suppose the number of reported cases is falling more rapidly than unreported cases. Young people are still getting sick at the same rate, but as before, they are not being counted as much.

Fatalities may be falling faster than total cases. That is hard to sort out from the data, because there is a 6-week lag from infection to death. If deaths are falling rapidly, this trend is probably real, because a large fraction of the elderly population has been vaccinated.

Quote from Fm1

I keep hearing that these vaccines can be adjusted but how many adjustments can be made to a vaccine that targets the spike protein? This could potentially create a vaccine resistant virus,

The experts in the mass media are sanguine. They say there is no likelihood the spike protein will evolve in a way that makes it resistant to reprogrammed mRNA vaccines. This particular form of coronavirus has a slow rate of change and it cannot change in ways the will be resistant to a reprogrammed vaccine, unlike some other viruses. They say the doctors must remain vigilant, and genotype testing has to be expanded to detect new variants, but they are confident the mRNA vaccines can be tweaked to deal with any emerging variant. It may require a third dose for people who got today's version.

That's what I read. The technical details are over my head.

One researcher who was interviewed seemed very confident of this. She said that this particular coronavirus is actually an easy target for a vaccine compared to others. Not to say it was easy to develop the vaccine, but once you have a vaccine, the virus is vulnerable and easy to kill off. I recall she also said the virus does not survive outside the body for long, unlike some others.

Quote from JedRothwell

The experts in the mass media are sanguine. They say there is no likelihood the spike protein will evolve in a way that makes it resistant to reprogrammed mRNA vaccines. This particular form of coronavirus has a slow rate of change and it cannot change in ways the will be resistant to a reprogrammed vaccine, unlike some other viruses. They say the doctors must remain vigilant, and genotype testing has to be expanded to detect new variants, but they are confident the mRNA vaccines can be tweaked to deal with any emerging variant. It may require a third dose for people who got today's version.

That's what I read. The technical details are over my head.

One researcher who was interviewed seemed very confident of this. She said that this particular coronavirus is actually an easy target for a vaccine compared to others. Not to say it was easy to develop the vaccine, but once you have a vaccine, the virus is vulnerable and easy to kill off. I recall she also said the virus does not survive outside the body for long, unlike some others.

This is an article from March of 2019 on mrna vaccines. Posted are some questions asked then that are still being asked now. How did Moderna and Pfizer answer these questions.

Advances in mRNA Vaccines for Infectious Diseases

https://www.frontiersin.org/ar…389/fimmu.2019.00594/full

Mechanism of Immune Response Induced by mRNA Vaccines

The immune response mechanism instigated by mRNA remains to be elucidated. The process of mRNA vaccine recognition by cellular sensors and the mechanism of sensor activation are still not clear. Intracellularly, two kinds of RNA sensors, endosomal toll-like receptors (TLRs) and the RIG-I-like receptor family, have been identified. The former set is divided into TLR-3, TLR7, TLR8, and TLR9, which are localized in the endosomal compartment of professional immune surveillance cells, such as DCs, macrophages and monocytes. TLR3 recognizes dsRNA longer than 45 base pair as well as dsRNA resulting from single strand RNA (ssRNA) forming secondary structures or derived from viral replication intermediates. TLR7 and TLR8 are activated by RNAs rich in polyuridines, guanosines and/or uridines. TLR7 can bind both dsRNA and single-stranded RNA (ssRNA), whereas TLR8 recognizes ssRNA only (123). TLR7 activation can increase antigen presentation, promote cytokine secretion and stimulate B cell responses (124). The latter family, functioning as a pattern recognition receptor (PRR), includes RIG-I, MDA5, and LGP2 (125). RIG-I preferentially recognize ssRNA and dsRNA bearing a 5′triphosphate, and stimulate IFN production (126–130). The panhandle structure in viral genome segments was directly involved IFNinduction through RIG-I activation (131). MDA5 is another cytosolic RNA sensor that detects long dsRNA generated during RNA virus replication (132) as well as RNA of synthetic origin, including poly I:C. Recognition by dsRNA induces the activation of IRF3 and NF-κB, subsequently leading to increased production of type I IFN (127, 133, 134). Sometimes, the elements of dsRNA recognized by PRR sensors can function as an adjuvant through the induction of IFN (135–137). mRNA vaccines can stimulate innate immunity through TLRs 3,7, and 8, RIG-I and MDA5 (138, 139). IFN induction by mRNA vaccines through RNA sensors is dependent on the quality of in vitro transcribed mRNA, delivery vehicle, and administration route. mRNA sensing by the innate immune system is a double-edged sword in the elimination of invading molecules. Natural exogenous mRNA stimulates strong induction of type I INFs and potent inflammatory cytokines, which instigate T and B immune responses but may negatively affect antigen expression (140–143). Interestingly, Blanchard and colleagues established a method to measure PRR activation by IVT mRNA in cells and in tissue section. In this method, proximity ligation assays (PLAs) was employed (144).

i.d. vaccination with the RNactive vaccine technology from CureVac AG, induced strong immune responses that are dependent on TLR7 signal. TLR7 activation leads to upregulation of chemokines, which in turn recruit innate immune cells such as DCs and macrophages to the site of injection (100). Activation of pro-inflammatory cytokines, such as TNF-α andIL-6 which are known to contribute to immune cells recruitment have been observed at the injection site (145).

On the other hand, an early shut-down of antigen expression after the mRNA vaccination due to PRRs activation might be detrimental. Consistently antigen expression, humoral and T cell responses to mRNA vaccination, both from conventional and amplifying mRNA, were significantly enhanced in IFNAR1/2 −/− mice (105, 146) or by co-administration of IFN antagonist (147). The negative impact from excessive IFN activation could derive not only from preventing RNA amplification, in case of self-amplifying mRNA vaccines, and expression, but also at the level of T cells. While type I IFN can determine the differentiation of antigen-primed CD8+ T cells into cytotoxic effectors, they may also promote T cell exhaustion (140). Whether type I IFN inhibits or stimulates the CD8 T cell response to mRNA vaccines might depend from the timing and intensity of type I IFN induced (140). T cell inhibition could prevail if triggering of type I IFN receptors precedes that of T cell receptors.

Modified mRNA with pseudouridines and mRNA purified with HPLC can reduce immune activation and increase antigen stability and expression (35, 148, 149). For an instance, i.p injection with mRNA containing pseudouridines induced antigen expression without the induction of cytokines in mice (150). Furthermore, some publications have shown that purity and delivery systems affect the immune response stimulated by mRNA vaccines (35). More interestingly, a recent study showed that modified mRNA encapsulated into LNPs has an adjuvant effect and induces a potent T follicular helper response and a large number of germinal center B cells with long-living, high affinity neutralizing antibodies (78).

Dentritic cell(DC) maturation is crucial to the effectiveness of mRNA-based vaccines. Generally, TLR7 was expresssed in plasmacytoid dentritic cells (pDCs) and B cells in humans, and TLR8 was expressed in conventional dentritic cells (cDCs), monocytes and macrophages. cDCs constitute the major resident DC population in normal human dermis and are characterized by CD1c expression (also known as blood dendritic cell antigen-1 (BDCA-1), whereas plasmacytoid DCs are present in the skin (129, 151, 152). The TLR7 and TLR8 locations in different DC subsets and DC locations in different organs may clarify the relationship between immune efficacy and the administration route and formulation of mRNA vaccines. Replacement of modified nucleotidesin mRNA decreased activation by binding mRNA to PRRs and reduced the innate immune response (153). mRNA vaccines not only stimulated the specific humoral immune response by the translated antigen but also the antigen-specific T cell response. Administration route and vaccine formulation determine the peak of antigen expression, which is another way to modulate the immune response (94, 154, 155). Liang et al. have shown that the kinetics of cell infiltration was largely similar between i.m. and i.d. administration in NHPs (156). The i.d. group showed stronger initial responses, probably because of rapid targeting, activation and transport to dLNs of skin DCs. Furthermore, only skin monocytes and DCs showed evidence of antigen translation at day 9, indicating prolonged antigen availability after i.d. delivery, and confirming the longer expression of mRNA-encoded antigen observed in mice (94).

A better elucidation of the sequence of events leading to mRNA translation and immune activation will help engineer mRNA vaccines to induce the correct balance of type I IFN induction, positively affecting vaccine outcome.

Clinical Trials

Compared with the prophylactic and therapeutic application of mRNA in cancer, clinical trials of mRNA vaccines for infectious disease are still in their early age. Pilot clinical trials with DCs transfected with mRNA encoding various HIV-1 antigens, cellular molecules, or pp65 of human cytomegalovirus showed that mRNA vaccines are safe and that they elicited antigen-specific CD4+ and CD8+ T cell immune responses; however, no reduction of viral load was observed (157–160).

In a recent clinical trial of protamine complexed mRNA vaccine against rabies virus, the results showed that RNA complexed with protamine is safe and well-tolerated in vivo, but efficacy was highly dependent on the dose and route of administration. The efficacy of administration with a needle-free device was much better than with direct needle injection (57, 161). Results of a phase I showed LNP-formulated modified H10N8 mRNA vaccine induced robust humoral immune response in volunteers with mild or moderate adverse reaction (108).

Prospective of RNA-based Vaccines

A plethora of publications have shown that mRNA-based vaccines are a promising novel platform that is high flexible, scalable, inexpensive, and cold-chain free. Most importantly, mRNA-based vaccines can fill the gap between emerging pandemic infectious disease and a bountiful supply of effective vaccines. A variety of preclinical and clinical projects have made enormous strides toward the conceivable application of mRNA vaccines and have suggested that mRNA-based prophylaxis and therapy can be translated to human applications. Although in medical application, magnitude of responses was lower than predicted from than those observed into animal models, the results of pilot clinical trials have shown good tolerability and that mRNA vaccination can induce antigen-specific T and B cell immune responses (57, 108). Therefore, mRNA holds great promises, but further insights into the mechanism of action and potency are still needed for full development of mRNA vaccines. The exploration of new strategies is needed to create applicable mRNA vaccines and to decrease the dose. As described above, the molecular impact of the innate immune response stimulated by mRNA through PAMP recognition is still not clear. Multiple efforts have been made to improve the stability and delivery efficiency of in vivo mRNA vaccine, including incorporation of 5′ and 3′ terminal untranslated regions and chemically modified nucleosides (162–164). Study demonstrated removal of dsRNA contaminants by high performance liquid chromatography purification of in vitro transcribed mRNA prolonged the translation (35). Research has demonstrated that modified nucleoside decreases the innate immune response and enhances protein expression. Optimization of the 5′-untranslated region (5′-UTR) of mRNA, whose secondary structures are recognized by cell-specific RNA binding proteins or PAMP molecules can maximize the translational yield of mRNA therapeutics and vaccines (43, 165). However, improper incorporation of modified nucleosides can have a negative impact on transcription products and increase costs.

Based on the results of the above described studies, a better understanding of the mechanism of action of mRNA vaccines, the identification and development of a new delivery system, and improvement of mRNA vaccine design will be attained (166).

mRNA vaccines have great potential and offer advantages over conventional vaccines. The growing body of preclinical and clinical results demonstrates that prophylaxis and therapy with mRNA promises to be useful for preventing infectious disease and treating tumors and that mRNA vaccines are safe and tolerated in animal models and humans. Additionally, future improvements should increase antigen-specific immune responses and the magnitude of memory immune cell responses, including memory B and T cell responses. Although mRNA vaccine technology has still not extensively tested in humans, publications of preclinical and early clinical tests have emerged in recent years, in which promising results were reported. This evoked the momentum of biocompanies to commercialize mRNA vaccines with great enthusiasm (167, 168). Some private funding resources and institutes have supported the research and development of mRNA vaccines (169, 170). Despite the need for further optimization of manufacturing processes to generate mRNA vaccines, these processes hopefully will be streamlined to be establish large-scale production. It is just a matter of time for RNA vaccines to be used in humans and animals.

Quote from Alan Smith

So, the pool of fully vaccinated citizens the report covers 677,000 people, and the reinfections total 4 cases.

Alan, you should not reproduce big pharma public relation statements. All in the above sentence is totally wrong. More than 1.6 mio. people are fully vaccinated in Israel. Choosing some of them makes no sense at all. Most likely Pfizer did choose people that are isolated in care homes. Also nobody ever did publish data just after the end of a vaccination. Usually you wait at least 3 months.

More serious is that hundreds of Israeli people got sick (with usual %age of death) due to the vaccination by the Pfizer vaccine as this is a known side effect during the first 2 weeks after the first shot.

All this you can see in the Worldometer data as a two week long extra peek with about 40-50 deaths due to vaccination promoted CoV-19.

more on vitamin D

Here some old stuff about how/what https://science.sciencemag.org/content/336/6088/1534/tab-pdfresearchers did before the mutated the bat virus.

Highly pathogenic avian influenza A/H5N1 virus cancause morbidity and mortality in humans but thus farhas not acquired the ability to be transmitted by aerosol or respiratory droplet (“airborne transmission”)between humans. To address the concern that the virus could acquire this ability under natural conditions,we genetically modified A/H5N1 virus by site-directed mutagenesis and subsequent serial passage inferrets.

The Obama action of stop: https://www.sciencemag.org/new…alls-voluntary-moratorium

Swiss background portal : https://swprs.org/ursprung-des…-minenarbeiter-hypothese/ (There is an English version too)

https://swprs.org/covid-19-virus-origin-the-mojiang-miners/

Covid-origin: The Mojiang-Mine workers event. Possibly this virus 96% match (still 1200 base mutations needed) has been used for further manipulations. Criminal action like fudging a DNA database and changing medical reports point to cover up action.

Quote from JedRothwell

Since none of that is happening, it isn't a problem, is it? Imaginary problems are not real problems.

“Group Think Red” believed, (some still do), that Covid-19 was an imaginary problem didn't they?

ALL of the data should be reviewed, not just the data that supports an opinion.

Quote from Navid

What contract did these people sign that they can't sign on to straightforward science about a well known drug with benefit to risk ratio through the roof!

And you know Dr. Hilton would be talking about "vaccine equality" and "racial justice with vaccines" and "vaccine nationalism" --- who's pulling their strings?

I like what Dr Kory says not what Dr. Hilton says. But somehow Dr. Hilton looks soooo much better when she says things.

She's a very smart cookie : "In just 4 short years she graduated Magnum Cum Laude from CofC with 3 degrees: two Bachelor of Science degrees in Biochemistry and Molecular Biology, and a Bachelor of Arts in Inorganic Chemistry."

She works at the Medical University of South Carolina specializing as an an anesthesiologist and is very knowledgeable in patient treatment and risk factors as it pertains to gender and race. She's a community activist, speaker and even authors childrens' books.

It seems she could be very influential in leading an ivermectin treatment charge. But she probably won't. She has a career in front of her and she is employed by a university hospital which is no doubt very heavily funded by big Pharma. I have little doubt she has been cautioned about what she can say. What else is new. Big business and big 'philanthropy' with their tentacles entwining throughout government, media, academia and healthcare agencies, has a chokehold on much of the world. Even smart people especially on the left don't seem to mind or care that money is speaking, often at the expense of the truth.

Quote from Roseland67

“Group Think Red” believed, (some still do), that Covid-19 was an imaginary problem didn't they?

ALL of the data should be reviewed, not just the data that supports an opinion.

There is no data. The assertion was pure fantasy. Let's review all of the data, shall we? The assertion was:

"If people are getting serous immune reactions or even dying from the vaccine, due to immune stimulation, or antibody dependent enhancement, or pathogenic priming, then saying the vaccine works is contra-reality."

FACTS:

People are NOT getting serious immune reactions. Only a few reactions have been reported, about the same number as from other vaccinations.

People are NOT dying from the vaccine. There has not been a single instance of that. None. Bupkis. Zero. If people were dying, it would be in all over the mass media. 178 million doses have been given and NOT A SINGLE PERSON HAS DIED FROM THE VACCINE. Got it? That's not surprising. Most vaccines kill fewer than 1 in a million, so you would expect ~178 deaths even if this were a particularly dangerous vaccine.

That's all of the data. The assertion by Navid is not data. It is bullshit from the Anti-Science Death Cult.

South Africa switches from Astrazeneca to J&J vaccine.. first jabs this week.

"“It’s incredible that we can switch so quickly,” Glenda Gray, president of the South African Medical Research council and a co-principal investigator of the J&J vaccine trial,

. “We were going to start the AstraZeneca program on Monday, and we are announcing the initiation of an alternative program to start the same week, which I think is phenomenal. The shift to the J&J was an important decision, because it’s the only vaccine that we knew would help against hospitalization and death.”

https://qz.com/africa/1973285/…johnson-covid-19-vaccine/

Quote from Mark U

It seems she could be very influential in leading an ivermectin treatment charge.

There is no need to lead any charge. Any doctor who wants to use ivermectin is free to do so. It is being widely used, even though most experts feel that tests show it does not work.

Quote from Mark U

She has a career in front of her and she is employed by a university hospital which is no doubt very heavily funded by big Pharma.

This statement makes no sense. Merck, the Big Pharma that makes the ivermectin, says it does not work! It discourages the use of this drug. Why would this company tell people not to use its own product? If it was only interested in making money, why would it not want people to use the drug? This is contrary to the company's interest. The drug has been proven safe when used in the proper doses, so the company has nothing to lose if doctors use it, and no risk of lawsuits, even though it is not effective against COVID-19. Off-label use is allowed in the U.S. even when there is no demonstrated efficacy.

Here is the Merck statement:

https://www.merck.com/news/mer…ng-the-covid-19-pandemic/

Merck Statement on Ivermectin use During the COVID-19 Pandemic

February 4, 2021 11:45 am EST

KENILWORTH, N.J., Feb. 4, 2021 – Merck (NYSE: MRK), known as MSD outside the United States and Canada, today affirmed its position regarding use of ivermectin during the COVID-19 pandemic. Company scientists continue to carefully examine the findings of all available and emerging studies of ivermectin for the treatment of COVID-19 for evidence of efficacy and safety. It is important to note that, to-date, our analysis has identified:

• No scientific basis for a potential therapeutic effect against COVID-19 from pre-clinical studies;
• No meaningful evidence for clinical activity or clinical efficacy in patients with COVID-19 disease, and;
• A concerning lack of safety data in the majority of studies.

We do not believe that the data available support the safety and efficacy of ivermectin beyond the doses and populations indicated in the regulatory agency-approved prescribing information.