Covid-19 News

And this (from the above paper) is why we still have not really got much of a clue about how to deal with COVID's effects, or how best to boost useful immune response to it:

Peripheral immune cells of COVID-19 patients were enriched in T cells, NK cells, and γδ T cells with a highly activated phenotype and elevated expression of genes associated with cytotoxic effector functions (GZMA, GZMB, GZMH, PRF1, GNLY, NKG7, and IL-32). We observed the presence of cytotoxic CD4 T cells in COVID-19 patients that were largely absent in healthy volunteers following immunization. While hyperactivation of inflammatory responses and cytotoxic cells may contribute to immunopathology in severe illness, in mild and moderate disease, these features are indicative of protective immune responses and resolution of infection^71,105. A multi-cohort analysis of immune responses across different viral infections showed that increased frequency of NK cells and expression of NK-associated genes is inversely correlated with severity¹⁰⁶. This is consistent with previous studies that show that reduced NK frequency and function are associated with increased tissue damage and severe COVID-19¹⁰⁷.

Our study, together with others, underscores the fine balance between antiviral immune responses that achieve clearance of the infection and durable protective immunity, and those that lead to inflammation and immunopathology. Better understanding of the immunological features associated with protective immunity, immunopathology, and durability of protective immunological memory will aid not only in better treatments for viral diseases, but also facilitate the rapid development of effective vaccines for new and re-emerging viral diseases that threaten public health.

Were I an anti-vaxxer - suspicious of long-term bad effects from anything that interferes with the immune system, I'd take this as obvious evidence (further proved by long COVID) that COVID infection, with its unique interference with the immune system, can deliver long-term damaging results. I'd see COVID as some sort of self-propagating sinister bio-engineered vaccine, and would therefore see vaccination, with a less extreme effect on the immune system, as less harmful. That would create a severe cognitive dissonance.

Since I'm not an anti-vaxxer I cannot draw such a conclusion, except this does underline my strong wish not to catch COVID, or at least not to catch severe COVID (milder versions have less effect on the immune system). If vaccines help with that (as they do) I'm for them.

Quote from Mark U

Happy "Freedom Day" for all the Brits out there! I hear most continue to wear their masks anyway. Still, "Freedom Day" sounds good doesn't it!

Did you hear the one about the French cafe owners who were told that in a few days, if they don't check their customers for a Covid pass, they can get up to a year in jail and a 45K Euro fine? Spoiler : it's no joke.

Freedom day has sounded increasingly stupid as the COVID rate here has climbed so dramatically. The mixed messages : "we want you to be free and take personal responsibility, you don't have to wear marks, but hey, look you need to be very careful and wear masks", have resulted in terminal confusion.

Luckily, we are used to this by now from Boris. For quite a while everyone has ignored what he has said and just done what they think best. It is not as good a response as when countries are well led, and it makes things difficult for business where you are damned either way, but it is the best we can do!

After saying that freedom day would be irreversible Boris has now said that come September a COVID pass will be needed for night clubs (double vaccination). There is speculation that the list of things you need this for will increase over the next few weeks in line with the apparently inexorable upward trend of COVID infection.

Other countries are seriously worried that we are creating a special UK whole-country breeding ground for optimally vaccine and (prior) infection evading new variants of COVID.

Quote from Fm1

Now Professor Martin shares with the world that the Pittsburgh-based VTU will conduct the mRNA vaccine investigating the safe dosage regimens for children 6 to 11 years old.

There are many more Dr. Mengeles on this planet. Keep in mind most doctors are of lowest grade intellect. A doctor needs other qualities. So if doctors do studies this is a bad sign.

Children age 0..12 have Zero risk from CoV-19. Ivermectin is safe for children too.

Once more the CoV-19 IFR from Swiss data::

1/3 of Switzerland has been infected so far =2.8 mio. Reported infections 0.7 mio. Under reporting 4x what is the value confirmed by many studies also in Germany.

Total deaths as of 19.07.2021 Death 10'900 --> IFR = 0.389 (Overall)

Age group > 65 97% of all death about 28% of population --> IFR 1.34

Age group < 65 IFR = 0.015

Age group < 25 IFR < 0.0001 deaths to few for calculation.

Hypothetical question regarding the proper dosage of Ivermectin paste to use if I feel that I have been exposed to COVID and have symptoms. I would like to work this out now so that I/we do not get the dosing wrong should we chose to use it in the future.

The ivermectin purchased is a paste containing 1.87% ivermectin sold in a 6.08-gram syringe tube. Directions state that the tube is sufficient to treat a 1250-pound horse at the recommended dosage of 91 mcg ivermectin per pound (200 mcg/Kg) body weight.

As I interpret it, the I-mask+ protocol for those exposed to and having symptoms of Covid calls for a dosage of 0.2mg/kg or 0.09 mg/lb. of body weight taken once a day for 5 days. The protocol is given by tablet, with each tablet containing 3mg ivermectin. However, the syringe tube I have is not marked in mg but with graduations of 250lb, 500lb, 750lb. 1,000lb and 1,250lb to achieve the concentrations outlined above.

It would seem that the dosage/lb. recommended for horses is virtually identical to the dosage recommended by the I-mask+ protocol for humans 0.09mg/lb. humans vs 0.091mg/lb. horses.

So, a 250lb person should take approximately 27.7 mg (250/0.09) of the paste per day. So, using the graduations on the tube one would express paste at the 250lb mark, correct? I would appreciate your input on this so that if the time ever comes to use it, I get it right.

Thank you in advance for your help!

Quote from Wyttenbach

as we in future will see much more vaccinated patients going to hospital (India! 9.8% instead of 2%).

W. Have you noticed how few of the hospital patients in the US are vaccinated, where vaccination is political so there is a significant proportion of the at-risk population that stays unvaccinated in some states? Those are the ones we see in hospital, together with a few of the vaccinated ones.

You keep on misunderstanding these number from India (and elsewhere).

You can properly point out that vaccine protection decreases as variants get further form the original virus. What you cannot do (and have informed people believe you) us say that the vaccine provides eitehr no or negative protection from hospitalisation relative to not being vaccinated. It provides strong positive protection.

I very seriously hope you do not go around telling other people that vaccines are anti-protective in this way. It might encourage them (if they are otherwise uninformed) not to take vaccines and therefore put themselves at unnecessary risk.

I apologise if I am misunderstanding what you are saying here.

Quote from THHuxleynew

Since I'm not an anti-vaxxer I cannot draw such a conclusion,

You should anyway not draw any conclusion unless you do read into immunology.

This paper confirms as many other papers before: Natural immunity from CoV-19 infection is much broader and does prevent reinfection much better than a vaccine. Then only positive I see from the vaccine that it lowers the death risk from the cytokine storm. But you will potentially pay this with a higher risk from all future viral infections because the induce antibodies really do harm (suppress interferon path mechanism is clear). Whether this harm is 1% or 10% larger ? or whether it(teh antibodies) will go away we don't yet know.

So for me there is more and more evidence that all the RNA/Astra vaccinated in future will have a more risky live.

This is from a fully vaccinated person that only takes seriously tested vaccines!

Quote from Wyttenbach

Children age 0..12 have Zero risk from CoV-19

Assessing the age specificity of infection fatality rates for COVID-19: systematic review, meta-analysis, and public policy implications - European Journal of Epidemiology

Determine age-specific infection fatality rates for COVID-19 to inform public health policies and communications that help protect vulnerable age groups.…

link.springer.com

Children age 10 certainly have a much lower IFR (0.002%) from COVID than older people, but it is not zero. The paragraph below is found by many people and pretty uncontentious. Worth noting thet UK regulators are still waiting for more information before agreeing COVID vaccination is worthwhile for anyone under 18. They recommend this in specific cases, but not universally. Regulators are very aware of that exponential curve and therefore that we need to be cautious. I think they may end up with a different view after we have more information about the risks of long COVID in children. We shall see.

Our analysis finds a exponential relationship between age and IFR for COVID-19. The estimated age-specific IFR is very low for children and younger adults (e.g., 0.002% at age 10 and 0.01% at age 25) but increases progressively to 0.4% at age 55, 1.4% at age 65, 4.6% at age 75, and 15% at age 85. Moreover, our results indicate that about 90% of the variation in population IFR across geographical locations reflects differences in the age composition of the population and the extent to which relatively vulnerable age groups were exposed to the virus. These results indicate that COVID-19 is hazardous not only for the elderly but also for middle-aged adults, for whom the infection fatality rate is two orders of magnitude greater than the annualized risk of a fatal automobile accident and far more dangerous than seasonal influenza. Moreover, the overall IFR for COVID-19 should not be viewed as a fixed parameter but as intrinsically linked to the age-specific pattern of infections. Consequently, public health measures to mitigate infections in older adults could substantially decrease total deaths.

Quote from Wyttenbach

You should anyway not draw any conclusion unless you do read into immunology.

This paper confirms as many other papers before: Natural immunity from CoV-19 infection is much broader and does prevent reinfection much better than a vaccine. Then only positive I see from the vaccine that it lowers the death risk from the cytokine storm. But you will potentially pay this with a higher risk from all future viral infections because the induce antibodies really do harm (suppress interferon path mechanism is clear). Whether this harm is 1% or 10% larger ? or whether it(teh antibodies) will go away we don't yet know.

So for me there is more and more evidence that all the RNA/Astra vaccinated in future will have a more risky live.

This is from a fully vaccinated person that only takes seriously tested vaccines!

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I do not claim to be an immunologist: and hope you would also not claim that.

What I do claim is to understand probability theory enough to make sense of the many different statistics around vaccination efficacy. I think your approach is to ignore all of that real-world evidence and stick with some theoretical view that somehow vaccination does not protect from hospitalisation? It may be that actually getting COVID protects more than vaccination: we do not yet have much evidence: that is not the point as long as vaccination reduces the risks from getting COVID. There is good evidence that getting COVID, followed by vaccination, is better than just getting COVID.

Take home: real-world evidence trumps theory.

Quote from THHuxleynew

And this (from the above paper) is why we still have not really got much of a clue about how to deal with COVID's effects, or how best to boost useful immune response to it:

Peripheral immune cells of COVID-19 patients were enriched in T cells, NK cells, and γδ T cells with a highly activated phenotype and elevated expression of genes associated with cytotoxic effector functions (GZMA, GZMB, GZMH, PRF1, GNLY, NKG7, and IL-32). We observed the presence of cytotoxic CD4 T cells in COVID-19 patients that were largely absent in healthy volunteers following immunization. While hyperactivation of inflammatory responses and cytotoxic cells may contribute to immunopathology in severe illness, in mild and moderate disease, these features are indicative of protective immune responses and resolution of infection^71,105. A multi-cohort analysis of immune responses across different viral infections showed that increased frequency of NK cells and expression of NK-associated genes is inversely correlated with severity¹⁰⁶. This is consistent with previous studies that show that reduced NK frequency and function are associated with increased tissue damage and severe COVID-19¹⁰⁷.

Our study, together with others, underscores the fine balance between antiviral immune responses that achieve clearance of the infection and durable protective immunity, and those that lead to inflammation and immunopathology. Better understanding of the immunological features associated with protective immunity, immunopathology, and durability of protective immunological memory will aid not only in better treatments for viral diseases, but also facilitate the rapid development of effective vaccines for new and re-emerging viral diseases that threaten public health.

Were I an anti-vaxxer - suspicious of long-term bad effects from anything that interferes with the immune system, I'd take this as obvious evidence (further proved by long COVID) that COVID infection, with its unique interference with the immune system, can deliver long-term damaging results. I'd see COVID as some sort of self-propagating sinister bio-engineered vaccine, and would therefore see vaccination, with a less extreme effect on the immune system, as less harmful. That would create a severe cognitive dissonance.

Since I'm not an anti-vaxxer I cannot draw such a conclusion, except this does underline my strong wish not to catch COVID, or at least not to catch severe COVID (milder versions have less effect on the immune system). If vaccines help with that (as they do) I'm for them.

Display More

Chance of long term COVID is a valid concern that should be considered for those still undecided about getting vaccinated. They have to weigh that, along with many other factors, against the risks of vaccine side effects.

To your credit, I think you have made a good argument that tips the balance a little more in favor of the vaccine...for me at least. Question is: where is the age cut-off where the vaccine risks outweigh the benefits? I am still far from convinced those under 30 need it, but then again, recently I was against those under 50 needing it.

And yes, I know you are for all ages, children included. Over time, and as the data accumulates, that may come to past. Who knows?

Quote from THHuxleynew

What I do claim is to understand probability theory enough to make sense of the many different statistics around vaccination efficacy.

I look at real data only as most doctors either cannot do the math/modelling properly or the result is given to them by big pharma.

As said. Phase III study of Pfizer real result from base data: Vaccinated got about 3x CoV-19 than unvaccinated.

Reason: Induced immune suppression by spike protein: See paper above and many others interferon path is blocked. This "immune suppression" only helps a bit for damping a strong infection.

By the way: Did you understand the Swiss IFR?

On The Battlefield of Misinformers, Dissenters & Staunch Stakeholders of the Almighty Narrative

On The Battlefield of Misinformers, Dissenters & Staunch Stakeholders of the Almighty Narrative

Note that views expressed in this opinion article are the writer’s personal views and not necessarily those of TrialSite. ErinKate Stair, MD, MPH

trialsitenews.com

ErinKate Stair, MD, MPH

Throughout the pandemic, I’ve worked as a public health analyst and have been part of several scientific communication initiatives dealing with how and what information is relayed to a particular audience. These include tasks like explaining how mRNA or viral vector-based vaccines work, using only plain language, and monitoring and dispelling myths about the vaccines. Right now, there is an aggressive campaign to purge misinformation from social media platforms. My main issue with this campaign is that, whatever the motive, scientific dissent is being incorrectly categorized as misinformation. Not surprisingly, a war over information has emerged on a digital battlefield crowded with Misinformers, Dissenters, Staunch Stakeholders of the Almighty Narrative and Confused-AF Spectators. This has allowed for keen observations related to strategy and tactics. Stay tuned for a self-published playbook on Amazon (that may even be available for purchase for a few days before being banned for violating something or other), but first I’d like to share some thoughts with you.

It’s important to acknowledge the existence of misinformation, or information that is false. If you don’t believe in misinformation, then you are essentially saying that everything you see or hear is true. Sometimes misinformation has a nefarious intention behind it, and then it’s called disinformation. Scientific dissent, however, is not misinformation. Scientific dissent is logical arguments, legitimate concerns and opinions, often expert ones, that challenge the overarching, scientific narrative. Dissenters might challenge pieces of that narrative or even all of it.

Scientific dissent is paramount, because it can help identify problems with a methodology, policy, drug, therapy, health program or even a widespread belief. I like to think of dissent as a Checks and Balances for science, ever important today when much of our medical system, regulatory bodies, health organizations and research agendas are under the spell of puissant pharmaceutical companies. They may not “love it when you call them Big Pharma” but big, they are.

Can you think of a time when scientific dissent was historically valuable? I mean, I hope so, as there are plenty of examples, one of which I’ll highlight: dissent concerning the relationship between the earth and the sun. Once upon a time, there was a man called Nicolaus Copernicus. He was an astronomer from Poland, and he was also a Dissenter. He published a book promoting a controversial theory about the earth revolving around the sun. At the time, everyone stood firmly behind the physics of Aristotle and believed the earth was the center of the universe, so they told Copernicus that his theory violated the science. If Copernicus had a Twitter or Facebook, he’d be branded a Misinformer and banned for spreading misinformation. You guys know who turned out to be right…, right? It’s not all the time, maybe not even half the time, that Dissenters prove correct, though it was the case with Copernicus.

Unfortunately, scientific dissent is not being recognized on social media platforms. It’s being misclassified as misinformation and banished. Now, I’m not a constitutional lawyer, but I believe private companies have the right to remove whatever content they want, and I’d only worry about a First Amendment violation if the government starts policing content for those companies. (Oh wait.) Either way, people deserve to know that these companies aren’t good at distinguishing misinformation from scientific dissent, and the baby will most likely get tossed with the bathwater.

In fairness, it can be extremely difficult to distinguish between misinformation and scientific dissent, which, given the importance of dissent, is an argument for doing away with censorship entirely. Others feel that misinformation can harm or even “kill” people, and therefore Misinformers, and the misinformation they spew, should be banned from every social media platform. But how is misinformation identified? It’s usually the job of “independent” fact checkers, sometimes journalists with no scientific background or journalists who consult with blue-check-mark scientists on Twitter who have similar biases and affiliations. And usually if information deviates from the almighty narrative, often dictated by a regulatory body, government or large health organization, it’s marked as misinformation. Scientific Dissenters are not invited to the fact-checking party, and why would they be? That would complicate the process, often create more questions than answers and sabotage the business plans of companies turning profits by posting the names of Misinformers as a righteous duty for all of humanity.

Another question is what to do with anecdotes. An anecdote is a person’s experience, so it’s hard to call that misinformation or dissent. Still, many anecdotes are purged from social media sites under the umbrella of misinformation. I don’t support deleting personal experiences, because I fear it could push someone over the edge, and since I don’t really know the person’s mental state or level of brainpower, I don’t want to be the one to tell that person to shut up and quit sharing. There isn’t a “test” to join a social media site, and not everyone has the same intellectual power or is a master of online discourse. Furthermore, the heart of the internet is the democratic sharing of information. No level of censorship can stop people from interacting. If sites ban them, they’ll create new digital places to exchange ideas. It’s no mystery why sites like BitChute, Telegram, Newtube and Odysee, not to mention private newsletter subscriptions, are growing. The war on misinformation is like fighting guerilla fighters who don’t care about holding terrain, can set up camp anywhere, and make it very difficult for the other side to declare victory.

Anecdotes may also be useful for the evolution of science and medical practice. For example, take some people’s experience with antidepressants and antidepressant withdrawal symptoms. Traditional medical wisdom was that withdrawal symptoms from antidepressants lasted up to two weeks. Regular people took to Twitter, Facebook and online forums to dispute that. They shared their experience of coming off antidepressants and having withdrawal symptoms lasting for a significantly longer time. While often accused of “pill-shaming” or being “anti-psychiatry” or spreading “dangerous misinformation”, they persisted in sharing their stories. Their persistence is why, for example, the UK’s National Institute for Health and Care Excellence and Royal College of Psychiatrists changed their guidance regarding antidepressant withdrawal symptoms.

No matter who gets classified as what, there are notable tactics and predictable responses on the battlefield of Misinformers, Dissenters and Staunch Stakeholders of the Almighty Narrative. Those who misinform, knowingly or not, latch on to Dissenters like parasites, so as to bolster their position and gain credibility. The Staunch Stakeholders of the Almighty Narrative love when this happens, because they use the Misinformers’ parasitic behavior to discredit the Dissenters. It’s the old guilt-by-association bit.

A dirty but highly effective tactic of the Staunch Stakeholders of the Almighty Narrative is to hit the Dissenters with reductive, stigmatizing labels. “Quack” is their favorite, and I’d argue excruciatingly overused. I recommend spicing it up a bit with alternatives like “Flimflammer” or William “Devil Bill” Rockefeller, not to be confused with the Rockefeller Center that just donated millions to fight misinformation, but the guy who was a famous Snake Oil Salesman. Other go-tos are “conspiracy theorist” or “anti-vaxxer” if you express an iota of concern about vaccines. Sometimes they disguise condescension as concern and ask questions like, “Is he/she okay?” or they treat Dissenters like radicals…, as if the Dissenter went from Gizmo to Stripe in a blink of an eye and can no longer be saved. Such pigeonholes can cost Dissenters their social media profiles, their reputations and even their jobs, and anyone considering dissention will observe this backlash and keep mum. Also, let me be clear about something: There are folks who could qualify as Quacks, but not everyone who gets called a Quack is a Quack. There are folks who could qualify as radicals, but not everyone who gets called a radical is a radical, and so on and so forth. The main thing the Dissenters should be wary of is to not become illogical or tribal due to the overwhelming bitterness and frustration that inevitably ensues. Meditation helps here, perhaps copious glasses of wine too.

What about the Confused-AF spectators? They simply observe the Cyber Charlie Foxtrot of Misinformers, Dissenters and Staunch Stakeholders of the Almighty Narrative and end up having no idea what or who to trust. Some might say their confusion is a reason to censor information, like forging a path through the forest for them so they don’t have to do it themselves. Others believe censorship will only fuel their distrust. For example, if you fear your significant other is cheating on you and want to know for sure, do you want to read all his/her text messages, or only the ones he/she shows you?

In conclusion, what one considers the best path forward probably comes down to personal, philosophical and political beliefs, but I think we can all agree that scientific dissent has propelled science forward, not backwards. Scientific dissent is information, not misinformation. Right now we lack tech overlords and consistent, unbiased fact checkers who can successfully distinguish scientific dissent from misinformation, and that’s a problem.

Quote from Bjohnk

0.2mg/kg or 0.09 mg/lb. of body weight taken once a day for 5 days.

the current protocol calls for 24 mg IVM daily for those over 40 kg...

there is no 0.2 mg/kg anymore..the target is now >=0.4

if your paste is 1.87% IVM

24 mg divided by 1.87% yields equivalent mass of paste...=`1.28 gm..

you cannot measure this accurately on a kitchen scale

there should be enough for 4.7 days at 24 mg/D dosing.

which is about 5 days..

Pragmatically I would use the Marked gradations to divide the total paste volume by 5..

As Shane says... ask a doctor at FLCCC.

Also do not rely on IVM alone... keep taking Vit D one 25mcg capsule per day... at least

Irish research ..

"It was also discovered that 47 per cent of people aged 18-39 are deficient in the vitamin. Thirty-five per cent of 50-59 year olds are also deficient.

"The report says that vitamin D supplementation of 20-25 micrograms per day should be recommended to the entire adult population, and higher doses should be recommended for vulnerable groups under medical supervision

Every adult in Ireland should take vitamin D supplements, report recommends

Urgency needed as deficiency linked to worse health outcomes for Covid patients

www.irishtimes.com

JAMA Pediatrics Editors Retract Children’s Mask Study

JAMA Pediatrics Editors Retract Children's Mask Study

Note that views expressed in this opinion article are the writer’s personal views and not necessarily those of TrialSite. Dr. Ron Brown – Opinion

trialsitenews.com

Trialsitenews.com recently reported a study published in JAMA Pediatrics on June 30, 2021, which found unacceptable levels of carbon dioxide in children wearing face masks. Needless to say, this was a very popular article. Children’s face masks increase carbon dioxide 6-fold over acceptable levels (trialsitenews.com). However, Trialsitenews.com has learned that the JAMA Pediatrics study was subsequently retracted by the journal editors on July 16, 2021. Notice of Retraction. Walach H, et al. Experimental Assessment of Carbon Dioxide Content in Inhaled Air With or Without Face Masks in Healthy Children: A Randomized Clinical Trial. JAMA Pediatr. Published online June 30, 2021. | Pediatrics | JAMA Pediatrics | JAMA Network.

The JAMA Pediatrics editors’ notice of retraction does not mention who raised scientific issues regarding the study’s methodology and other concerns, or reveal all the detailed evidence supporting the specific concerns raised, or identify possible conflicts of interest by the parties raising the concerns. Nor were the study authors’ responses to the concerns revealed.

During these times of unprecedented censorship, it is difficult to accept the legitimacy of this retraction on face value alone, especially considering that Facebook censored the original article when it was first published in JAMA Pediatrics. Facebook warns JAMA study on children’s COVID masks ‘false news,’ sharers will be punished | Just The News.

Furthermore, neither of the journal’s two editors holds doctoral degrees, which requires advanced knowledge of research methodology, inferring that the editors may have over-relied on outside sources for “additional scientific review.”

The editors are right about at least one point—the retracted study has “potential public health implications.” In view of the great significance to public health concerning the issue of masks and children’s health, the public should have access to all details of the specific concerns raised, and the authors’ complete responses, so that an open debate can fairly review and discuss the retracted the study.

Even if an open critical appraisal supports problems in methodology, this should not automatically disqualify the thesis of the study. I can’t think of a single study that doesn’t have methodological limitations. It is simply not possible to address every single issue in one study. More importantly, publishing study limitations helps point the direction toward designing further studies to continue to pursue the investigation.

It’s not likely that any one study is capable of establishing the final word on this issue, and many more studies should continue to investigate carbon dioxide exposure in children wearing masks. However, criticizing a study’s validity based on design limitations is one thing, which happens frequently in the research literature, but it is quite another to retract a study from the scientific research literature altogether. Even a weak study can function within the literature as an exploratory investigation, which is intended to present the feasibility of the study, upon which other researchers can improve with stronger designs.

Only through shared information in the research literature can further studies zero in on resolving vitally important issues. In the meantime, chopping off the children’s mask investigation at the root by retracting the current study potentially censors the scientific literature, which is unacceptable. The message sent is loud and clear: This topic is off limits. We don’t want to know!

Single cell profiling of T and B cell repertoires following SARS-CoV-2 mRNA vaccine

Single cell profiling of T and B cell repertoires following SARS-CoV-2 mRNA vaccine

mRNA based vaccines for SARS-CoV-2 have shown exceptional clinical efficacy providing robust protection against severe disease. However, our understanding of…

www.biorxiv.org

ABSTRACT

mRNA based vaccines for SARS-CoV-2 have shown exceptional clinical efficacy providing robust protection against severe disease. However, our understanding of transcriptional and repertoire changes following full vaccination remains incomplete. We used single-cell RNA sequencing and functional assays to compare humoral and cellular responses to two doses of mRNA vaccine with responses observed in convalescent individuals with asymptomatic disease. Our analyses revealed enrichment of spike-specific B cells, activated CD4 T cells, and robust antigen-specific polyfunctional CD4 T cell responses in all vaccinees. On the other hand, CD8 T cell responses were both weak and variable. Interestingly, clonally expanded CD8 T cells were observed in every vaccinee, as observed following natural infection. TCR gene usage, however, was variable, reflecting the diversity of repertoires and MHC polymorphism in the human population. Natural infection induced expansion of larger CD8 T cell clones occupied distinct clusters, likely due to the recognition of a broader set of viral epitopes presented by the virus not seen in the mRNA vaccine. Our study highlights a coordinated adaptive immune response where early CD4 T cell responses facilitate the development of the B cell response and substantial expansion of effector CD8 T cells, together capable of contributing to future recall responses.

The BNT162b2 mRNA vaccine against SARS-CoV-2 reprograms both adaptive and innate immune responses

Summary

The mRNA-based BNT162b2 vaccine from Pfizer/BioNTech was the first registered COVID-19 vaccine and has been shown to be up to 95% effective in preventing SARS-CoV-2 infections. Little is known about the broad effects of the new class of mRNA vaccines, especially whether they have combined effects on innate and adaptive immune responses. Here we confirmed that BNT162b2 vaccination of healthy individuals induced effective humoral and cellular immunity against several SARS-CoV-2 variants. Interestingly, however, the BNT162b2 vaccine also modulated the production of inflammatory cytokines by innate immune cells upon stimulation with both specific (SARS-CoV-2) and non-specific (viral, fungal and bacterial) stimuli. The response of innate immune cells to TLR4 and TLR7/8 ligands was lower after BNT162b2 vaccination, while fungi-induced cytokine responses were stronger. In conclusion, the mRNA BNT162b2 vaccine induces complex functional reprogramming of innate immune responses, which should be considered in the development and use of this new class of vaccines.

Quote from Wyttenbach

I no this dissipative reports made by the pharma clerks. They do not use proper math. If cloths occur within 3-6 hours then you must take the survival rate for e.g. 1/8 of a day. Then you must take a mirror set of same age groups and look often such people did die after the flu shot within 3-6 hours. Crucial is the time point of onset of symptoms not the final death. You can always cheat this. A said in VAERS you can find a large set of cases with all details.

Survival rate calculations is done all the time by scientists. Yes the clerks that get the reports will read and fill in the database and what not I do not know the exact details, but the statistics is handled by experts, and they know how to analyze life data. Typically you make a Kapplan Meyer Graph For the subgroup of interest. The software knows how to correct for fractions of days.

Yes studying the onset of symptoms in stead of actual death can lead to a sharper tool to find out issues with medicines. So the reason is this.

If you get a symptom in a sharp time period (a peak) after the vaccine shot, we would expect that due to the big variation of responses, the actual time to death will smooth out the peak and it can hide in the background noise. On the other hand we know the background of deaths and the onset should have the same rate as deaths as both timepoints are very flat during a week time scale and has the same frequency if we do not count onsets from people that survive hence the same. Now how could we get hold on that data?, are the medical records that exact? VERS has onsets but is not complete - people tend to report more if it is closer to the jab time. One could go through all medical records and do the statistics on the onset rate just as with deaths, that could probably be an innovation but how reliable is this information. Also a possibility, but less powerful but more easy to get statistics to use is the time when people is hospitalized. I find this approach really interesting. I will ask my friend about this.

Thomas, here's your chance. Think about it, you'd be good at this!

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Quote from Shane D.

Chance of long term COVID is a valid concern that should be considered for those still undecided about getting vaccinated. They have to weigh that, along with many other factors, against the risks of vaccine side effects.

To your credit, I think you have made a good argument that tips the balance a little more in favor of the vaccine...for me at least. Question is: where is the age cut-off where the vaccine risks outweigh the benefits? I am still far from convinced those under 30 need it, but then again, recently I was against those under 50 needing it.

And yes, I know you are for all ages, children included. Over time, and as the data accumulates, that may come to past. Who knows?

Just a correction.

I don't think my ball park calculations can easily second guess the regulators. Thus far we have:

FDA 12+

MHRA (UK) 18+ with a few exceptions for 12+

Were it my children < 18 i would not be too bothered either way (for them). < 12 it would not be allowed anyway.

> 18 the risk/benefit analysis is very clearly in favour of vaccine.

While that is my view as far as personal risk of death goes at the moment, it will probably change in favour of vaccine. And in the US where > 12 is allowed I'd look very foolish if I did not encourage a child to get vaccinated, and the child then ended up with long COVID symptoms for a year. That is a relatively high chance.

The other issue is collective society risk. The more people are vaccinated the faster we can get to a position where COVID rates go down and things can be more normal. We will not (anywhere) get herd immunity just from vaccine because delta is so highly infectious. We can achieve herd immunity (I hope) through vaccine + people catching COVID., And the vaccine can very gretaly reduce the cost of this in terms of deaths and long COVID future burden.

One more thing - the chances of a newer nastier variant emerging, and effecting everyone badly, is directly proportional to the COVID rate. So given that high vaccination rates reduce that (eventually) that is another reason to gte vaccinated if your personal risk judgement is unclear either way.

THH

Quote from THHuxleynew

Peripheral immune cells of COVID-19 patients were enriched in T cells, NK cells, and γδ T cells with a highly activated phenotype and elevated expression of genes associated with cytotoxic effector functions (GZMA, GZMB, GZMH, PRF1, GNLY, NKG7, and IL-32). We observed the presence of cytotoxic CD4 T cells in COVID-19 patients that were largely absent in healthy volunteers following immunization. While hyperactivation of inflammatory responses and cytotoxic cells may contribute to immunopathology in severe illness, in mild and moderate disease, these features are indicative of protective immune responses and resolution of infection71

Do you really understand it or must I explain it one more time ??

Only in the rare case of a severe infection a vaccine antibody response could be better than natural immunization. In all other mild to medium severe cases vaccines are much worse. This explains the 40: 1 ratio of breakthrough infections/v.s. re-infection!

Quote from THHuxleynew

I very seriously hope you do not go around telling other people that vaccines are anti-protective in this way.

I tell people if they did use the crappy Pfizer/Astra vaccine to keep Ivermectin,Quercetin,V-D,zinc ready in case they get symptoms as their chance to get a severe reaction is much higher than from a natural infection. Also the time to react on symptom onset with delta is much shorter!

I never did recommend vaccination for people age <65 or without severe comorbidity. Only criminals can recommend experimental untested vaccines to people age < 65 without comorbidity, as the IFR is lower than from flu.

Quote from Fm1

AMA Pediatrics Editors Retract Children’s Mask Study

Already the idea to give children age < 12 masks shows the criminal intent of the acting people.

Once more: Switzerland never recommended masks for children. Not even in the most crowded location of a superstore. We never closed schools for children, what did kill (0 = zero) a large number of them....

Quote from stefan

If you get a symptom in a sharp time period (a peak) after the vaccine shot, we would expect that due to the big variation of responses, the actual time to death will smooth out the peak and it can hide in the background noise

For me people with symptom onset within max 3-6 hours after jab are 100% vaccine deaths within 24..48 hours need a more carefully look. Exceptions are the myocarditis cases that usually die 4 weeks later as symptoms do onset much later > 1 week. So most likely heart stroke vaccine victims (5/mio vaccines US military data) will never end up in VAERS etc..