The Playground

Vitamin D and marine omega 3 fatty acid supplementation and incident autoimmune disease: VITAL randomized controlled trial

Abstract

Objective To investigate whether vitamin D and marine derived long chain omega 3 fatty acids reduce autoimmune disease risk.

Design Vitamin D and omega 3 trial (VITAL), a nationwide, randomized, double blind, placebo controlled trial with a two-by-two factorial design.

Setting Nationwide in the United States.

Participants 25 871 participants, consisting of 12 786 men ≥50 years and 13 085 women ≥55 years at enrollment.

Interventions Vitamin D (2000 IU/day) or matched placebo, and omega 3 fatty acids (1000 mg/day) or matched placebo. Participants self-reported all incident autoimmune diseases from baseline to a median of 5.3 years of follow-up; these diseases were confirmed by extensive medical record review. Cox proportional hazard models were used to test the effects of vitamin D and omega 3 fatty acids on autoimmune disease incidence.

Main outcome measures The primary endpoint was all incident autoimmune diseases confirmed by medical record review: rheumatoid arthritis, polymyalgia rheumatica, autoimmune thyroid disease, psoriasis, and all others.

Results 25 871 participants were enrolled and followed for a median of 5.3 years. 18 046 self-identified as non-Hispanic white, 5106 as black, and 2152 as other racial and ethnic groups. The mean age was 67.1 years. For the vitamin D arm, 123 participants in the treatment group and 155 in the placebo group had a confirmed autoimmune disease (hazard ratio 0.78, 95% confidence interval 0.61 to 0.99, P=0.05). In the omega 3 fatty acids arm, 130 participants in the treatment group and 148 in the placebo group had a confirmed autoimmune disease (0.85, 0.67 to 1.08, P=0.19). Compared with the reference arm (vitamin D placebo and omega 3 fatty acid placebo; 88 with confirmed autoimmune disease), 63 participants who received vitamin D and omega 3 fatty acids (0.69, 0.49 to 0.96), 60 who received only vitamin D (0.68, 0.48 to 0.94), and 67 who received only omega 3 fatty acids (0.74, 0.54 to 1.03) had confirmed autoimmune disease.

Conclusions Vitamin D supplementation for five years, with or without omega 3 fatty acids, reduced autoimmune disease by 22%, while omega 3 fatty acid supplementation with or without vitamin D reduced the autoimmune disease rate by 15% (not statistically significant). Both treatment arms showed larger effects than the reference arm (vitamin D placebo and omega 3 fatty acid placebo).

Study registration ClinicalTrials.gov NCT01351805 and NCT01169259

Quote from ZenoOfElea

However, for those saying the pandemic is now "over" I would say that may be true in some parts of the world but in many other parts that do not have the access to medical treatments that the USA and Europe have then Covid is still a significant threat and there remains the likelyhood of further variants arising.

Ironically this is not true. Third world like Africa India does far better than UK with low cost Ivermectin treatment. India - the Ivermectin treatment country - just had a short Omicron peak with little death except Kerala (gene therapy only)...

Ivermectin work brilliantly for Omicron just some factor more reliable as for delta. This is also confirmed by today's Newspaper posts e.g. in Zeit that again warn of the poisonous drug Ivermectin...

Omicron is not CoV-19. No deep lung attacks no ICU. If somebody tells you ICU load with Omicron does increase then this is fear mongering. Yes: ICU with Omicron does increase because traffic victims, Cancer folks, heart attacks etc.. are diagnosed upon entry...

Zürich had no Omicron admission to ICU.

'1 in 3 dies, should we worry': Wuhan scientists warn of new Covid virus 'NeoCov' with high death rate and spread, says Report

According to researchers, only one mutation is required for the virus to infiltrate human cells

'1 in 3 dies, should we worry': Wuhan scientists warn of new Covid virus 'NeoCov' with high death rate and spread, says Report

Scientists from China’s Wuhan, where the Covid-19 virus was first discovered in 2019, have warned of a new type of coronavirus ‘NeoCov’ in…

m.tribuneindia.com

Chandigarh, January 28

Scientists from China’s Wuhan, where the Covid-19 virus was first discovered in 2019, have warned of a new type of coronavirus ‘NeoCov’ in South Africa, stated to have a high death and transmission rate, according to a report by the Russian news agency Sputnik. The new variant of NeoCov virus is not new, says report.

Associated with the MERS-CoV virus, it was discovered in outbreaks in Middle Eastern countries in 2012 and 2015 and is similar to the the SARS-CoV-2, which causes coronavirus in humans.

While NeoCoV was discovered in a bat population in South Africa and has only been known to spread among these animals, a new study published as a preprint on the bioRxiv website discovered that NeoCoV and its close relative PDF-2180-CoV can infect humans.

According to researchers from Wuhan University and the Chinese Academy of Sciences’ Institute of Biophysics, only one mutation is required for the virus to infiltrate human cells.

The research findings stated that the novel coronavirus poses a risk because it binds to the ACE2 receptor differently than the coronavirus pathogen. As a result, neither antibodies nor protein molecules produced by people with respiratory diseases or who have been immunised can protect against NeoCoV.

According to Chinese researchers, NeoCoV carries the potential combination of MERS-high CoV’s mortality rate (one in every three infected person dies) and the current SARS-CoV-2 coronavirus’s high transmission rate.

Following a briefing on NeoCoV, experts from the Russian State Virology and Biotechnology Research Center issued a statement on Thursday, the report stated.

Close relatives of MERS-CoV in bats use ACE2 as their functional receptors

Middle East Respiratory Syndrome coronavirus (MERS-CoV) and several bat coronaviruses employ Dipeptidyl peptidase-4 (DPP4) as their functional receptors.…

www.biorxiv.org

Looks like its mutated again with this new 'NeoCov' strain. Should kill off all our pensioners in care homes and inundate the NHS. Self-isolate, self-isolate, self-isolate.

Quote from Fm1

Vitamin D and marine omega 3 fatty acid supplementation and incident autoimmune disease: VITAL randomized controlled trial

https://www.bmj.com/content/376/bmj-2021-066452

Abstract

Objective To investigate whether vitamin D and marine derived long chain omega 3 fatty acids reduce autoimmune disease risk.

Design Vitamin D and omega 3 trial (VITAL), a nationwide, randomized, double blind, placebo controlled trial with a two-by-two factorial design.

Setting Nationwide in the United States.

Participants 25 871 participants, consisting of 12 786 men ≥50 years and 13 085 women ≥55 years at enrollment.

Interventions Vitamin D (2000 IU/day) or matched placebo, and omega 3 fatty acids (1000 mg/day) or matched placebo. Participants self-reported all incident autoimmune diseases from baseline to a median of 5.3 years of follow-up; these diseases were confirmed by extensive medical record review. Cox proportional hazard models were used to test the effects of vitamin D and omega 3 fatty acids on autoimmune disease incidence.

Main outcome measures The primary endpoint was all incident autoimmune diseases confirmed by medical record review: rheumatoid arthritis, polymyalgia rheumatica, autoimmune thyroid disease, psoriasis, and all others.

Results 25 871 participants were enrolled and followed for a median of 5.3 years. 18 046 self-identified as non-Hispanic white, 5106 as black, and 2152 as other racial and ethnic groups. The mean age was 67.1 years. For the vitamin D arm, 123 participants in the treatment group and 155 in the placebo group had a confirmed autoimmune disease (hazard ratio 0.78, 95% confidence interval 0.61 to 0.99, P=0.05). In the omega 3 fatty acids arm, 130 participants in the treatment group and 148 in the placebo group had a confirmed autoimmune disease (0.85, 0.67 to 1.08, P=0.19). Compared with the reference arm (vitamin D placebo and omega 3 fatty acid placebo; 88 with confirmed autoimmune disease), 63 participants who received vitamin D and omega 3 fatty acids (0.69, 0.49 to 0.96), 60 who received only vitamin D (0.68, 0.48 to 0.94), and 67 who received only omega 3 fatty acids (0.74, 0.54 to 1.03) had confirmed autoimmune disease.

Conclusions Vitamin D supplementation for five years, with or without omega 3 fatty acids, reduced autoimmune disease by 22%, while omega 3 fatty acid supplementation with or without vitamin D reduced the autoimmune disease rate by 15% (not statistically significant). Both treatment arms showed larger effects than the reference arm (vitamin D placebo and omega 3 fatty acid placebo).

Study registration ClinicalTrials.gov NCT01351805 and NCT01169259

Display More

This is an interesting win for Vit D.

The results look significant to me, and reducing autoimmune disease could have knock-on good effects.

Contrast this with many other claimed benefits of Vit D that alas have not held up to double-blind RCT scrutiny.

Yes, but don't be disappointed, these Anti-Bat anti-virals from the start have to be taken in combination.

US scientists who downplayed COVID-19 lab leak origins theory sang a different tune in private, emails show

US scientists who downplayed COVID-19 lab leak origins theory sang a different tune in private, emails show

American scientists who publicly attributed the COVID-19 pandemic to natural origins rather than human engineering were far less confident in private,…

www.foxnews.com

U.S. scientists who publicly attributed the COVID-19 pandemic to natural origins rather than human engineering were far less confident in private, transcripts and notes from previous meetings show.

However, conversations between public officials seem to indicate that some experts may have consciously chosen to suppress evidence that could fuel "conspiracists."

"I really can't think of a plausible natural scenario where you get from the bat virus ... to nCoV where you insert exactly four amino acids 12 nucleotide that all have to be added at the exact same time to gain this function," Dr. Robert Garry from Tulane's School of Medicine said, according to notes from a February 2020 meeting released by House Republicans.

NEW INTEGRAL DOCUMENTS REVEAL COVID ORIGINS DOWNPLAYED

"I just can't figure out how this gets accomplished in nature," Garry added in his group comments at the time. "Don't mention a lab origin, as that will just add fuel to the conspiracists."

Now, fresh questions are being raised about what American scientists and federal health officials knew about the origins of the coronavirus and whether conflicting evidence was suppressed and hidden from the public.

White House medical advisor Dr. Anthony Fauci was warned as early as Jan. 27, 2020, that the National Institute of Allergy and Infectious Diseases (NIAID) he oversaw was indirectly linked to the infamous Wuhan lab through EcoHealth, a U.S.-based scientific nonprofit that had been working with novel coronaviruses.

NIAID Principal Deputy Director Hugh Auchinloss floated the idea to Fauci that the research partially tied to the U.S. government may not have gone through the appropriate biosafety evaluations, saying that he will "try to determine if we have any distant ties" to the facility

(NIH) and the state of medical research on Capitol Hill in Washington, D.C., May 26, 2021. (Sarah Silbiger/POOL/AFP via Getty Images)

Dr. Kristian Anderson, a prominent virologist at the Scripps lab, told Fauci Jan. 31 2020, that "the genome is inconsistent with expectations from evolutionary theory," an observation that points to synthetic manufacturing.

After Fauci was made aware of Anderson's observations, a conference call with dozens of expert virologists around the world was organized.

Dr. Mike Farzan, another researcher at the Scripps lab, expressed doubts about the virus's origins in nature at the time as well. However, Fauci and others in the meeting pointed to evidence that the virus originated in a seafood and wild animal market in Wuhan.

Investigation into the food hypothesis was complicated by the suspected market being shut down and scrubbed clean by Chinese authorities before a full analysis could be performed.

By the end of the meeting, then-National Institutes of Health Director Francis Collins had tentatively sided with the natural causation theory, stating that an emphasis on blame for the outbreak could threaten "international harmony."

"I am coming around to the view that a natural origin is more likely," Collins wrote at the time. "But I share your view that a swift convening of experts in a confidence inspiring framework (WHO seems really the only option) is needed, or the voices of conspiracy will quickly dominate."

Just four days later, five researchers who were on the call authored preliminary findings abandoning their early private beliefs that the virus was likely the result of a lab leak. The March 17, 2020, article published in Nature Medicine stated, "Our analysis clearly shows that [COVID] is not a laboratory construct or a purposefully manipulated virus."

The concerns and questionable evidence originally debated by experts just months earlier were not just dismissed but went completely unacknowledged in the article's analysis. It is unclear what new evidence prompted the reversal of opinion, but private communications show that various drafts were sent to Fauci and Collins for approval.

Individuals within the federal government continued to consciously suppress accusations of human involvement with the COVID-19 outbreak despite the standing evidence against such a theory.

After then-President Trump said he would not discount the theory that the virus spread from a Chinese wet market due to unsafe hygiene practices, Collins wrote to Fauci, "Wondering is there something NIH can do to put down this very destructive conspiracy."

"I would not do anything about this right now. It is a shiny object that will go away in time," Fauci assured Collins.

At an April 17 press conference, Fauci assured the public that the makeup of COVID-19 was in line with what could be expected from a natural virus.

All the way up until his last days in office, Collins continued to focus on natural explanations of the pandemic.

In an interview near the end of his time at the head of the NIH, Collins did not outright deny any possibility of human influence on the virus, but he stopped short of entertaining the idea COVID-19 was made from the ground up.

I don't think I have any more new information to be able to tip the balance," he said. "Certainly possible that this was somehow under study in the lab even though it was not human engineered from scratch, I am quite confident of that."

Collins stood by the natural cause hypothesis through the rest of his time in his position.

On the guidance of world virology experts, Facebook actively suppressed reporting on the lab leak theory, utilizing "false information" warnings and listing relevant investigations as "debunked" until May 2021.

The Smithsonian’s National Portrait Gallery announced its 2022 Portrait of a Nation Honorees on Wednesday with a list that includes Chief Medical Adviser to the President Dr. Anthony Fauci.

"We are proud to introduce the 2022 Portrait of a Nation Honorees who embody creativity, individuality, excellence, and service to the people of our country," the Smithsonian National Portrait Gallery said in a statement revealing that Fauci, along with six others will be honored at a November gala to "celebrate seven remarkable individuals for their transformational impact on the nation’s history, development, and culture."

Quote from THHuxleynew

This is an interesting win for Vit D.

The results look significant to me, and reducing autoimmune disease could have knock-on good effects.

Contrast this with many other claimed benefits of Vit D that alas have not held up to double-blind RCT scrutiny.

This is exactly the point to many posters frustration with the pandemic response and often yours....., almost more so than the mRNA treatments.....

Many have said here since day one... two years ago.... that vitamin D, Zinc and quercetin had known immune system benefits. That EVEN if they did not help much against Covid, there were many good reasons to take it anyway.... thus in light of the many reports that it helped Covid outcomes, governments should have been pushing this as much as masks and hand washing at least.

But no.... it was not THE mRNA jab and anything that may distract from those had to be demonized. Not a peep about D, Zn or other. Silence or even demonizing.

How many peoples lives would have been saved if there had been a national campaign to take the readily available D, Zinc and possible a few other compounds IN ADDITION to the mRNA jabs since Jan. 2020? I suspect a lot!

But it was the vaccine warriors all out campaign against everything other than the mRNA jabs that was stopping this.

I have taken Ivermectin twice now. the latest was yesterday as I felt symptoms coming on. Significant symptoms as in low grade fever ...99, a small cough, scratchy throat. As in many places, Omicron is active here. Both times the next morning (12 hours) I was symptom free and no "deathly side affects". Proof? not really.... will I take it again... 100% certainty....

I know of 3 local people who died this week... all twice jabbed and boostered to no avail as the hospital did little to help other than ventilate and all victims were younger than 60! Main stream medical treatment concerning Covid is a death sentence.

I am caring for my 91 year old mother.. (fully vaccinated)... but she cannot risk getting ANY covid. For me to "do nothing" is simply unacceptable.... .which is what the major medical field does, until you get so bad they can put you on a ventilator. And we all know, even you admit that being vaccinated does not stop one from getting or transmitting the virus.

What are you going to say when it comes out that Ivermectin actually does work as promoted? I know this is a bold statement, but I feel it is going to be so, however, it may be well into the future as it surely will be kept buried as long as possible.

Will your many, many posts aggressively against Ivermectin be worth the lives it would have saved? Remember, just like Vit. D, doctor prescribed Ivermectin is so safe that there is no downside it taking it...... there were no alternatives the past two years.

Low risk and possible protection, was immediately available, could be self administered... just like D, ZN and others?

In the meantime.... "Damn if anyone should take it because there was not a double blind, RCT done by Phizer" all while hundreds of thousands die.... the scores of other positive trials MUST be demonized as well.

"Follow the science my ass"! I should compile a post here that shows what countries are discontinuing mRNA jabs for young people versus those like the US who are demonizing those who do not fall in line... where is the science in that? Sincerely!

WHO has several conflicting policies versus the US.... which is following the science?

Of the 70 plus positive studies for ivermectin having hundreds of qualified researchers from several countries involved.... all evidently are incompetent because THH says those studies do not meet his approval and do not amount to ANY evidence at all and that ivermectin MUST be demonized?

So again, during two years when there was no treatment, there were some very, very safe compounds with 30+ year histories and 70+ reports showing that these compounds helped.

But simply because they did not meet ones own yard stick, they had to be demonized and fought against at all costs. Patients were left to die on ventilators because ivermectin, D, Zn etc. did not follow the agenda.

Your response probably will be... the trials were bad, Ivermectin will not work and thus this is all moot and emotional argument. Well...this same argument was about D we were saying the same thing as well were we not...... and as more info comes out, who was right?

This is quite sad really....and who is "following the science"...?????

It would be very nice to meet you some day and set down and have a cup of coffee... it really would! But the with the "Vaccine passports" being mandated from those that "follow the science", that may never happen!

Quote from THHuxleynew

Whether this embalmer is really seeing more white fibrous clots than normal I would not want to judge, but if he were, the obvious reason would be the upsurge in COVID cases. As we know, COVID has now one way or another infected mots of the world's population. We know that it permeates the body and produces both unusual bleeding of blood vessels and blood clotrs.

It could be due to Covid infection, yes. The embalmer admitted he didn't have proof to tie it to the vaccine, only that he started noticing the unusual clots in late 2020. Mount Sinai did autopsies in spring of 2020 and found unusual clotting patterns but noted nothing about long fibrous white clots.

Mount Sinai Analysis of COVID-19 Autopsies Reveals Many New Details About This Disease | Mount Sinai - New York

Quote from ZenoOfElea

But I thought it was Fauci and the Covid mafia that were spreading the scary propaganda to use fear to control people.

Looks like both sides are at it.

One video and one embalmer sharing his findings is not propaganda! Geez. If you want real propaganda, come to Canada.

Quote from Mark U

One video and one embalmer sharing his findings is not propaganda! Geez. If you want real propaganda, come to Canada.

I think there have been other claims from the anti-vaxx side that "vaccines turn you into crocodiles" (Jair Bolsonaro). OK I know that Bolsonaro was not being serious .

But others have said vaccines will kill you or mutate your DNA etc.

So I stand by my claim that both sides are guilty of fear-mongering.

Quote from ZenoOfElea

But others have said vaccines will kill you or mutate your DNA etc.

So I stand by my claim that both sides are guilty of fear-mongering.

To much TV makes you impotent... Drinking 6l water kills you... Driving drunk is fun...for who?

The real problem are so called fact checkers that give you fake results for such questions like ivermectin = poison or CoV-19 gene therapy is harmless or has been tested for years...

Money = the FM/R/J/B mafia likes to define your world - so it is much easier to predict share prizes and they know all business opportunities in advance...

50!!!! state deputies of the Former German ruling party CDU have been involved in fraudulent mask deals...Certainly many more in USA...Money is the real drug/disease that poisons your brain and unluckily no vaccine exist for this disease.

A fool per definition is a person that himself is not able to recognize/understand the truth/facts. Fools need help <--> fact checkers --> (fool)² !

The UK seems to have written off around £4.7Bn in fraudulent Covid support payments, some made to newly formed companies that were not even trading.

TFF Pharmaceuticals Advancing Niclosamide, an Inhaled COVID-19 Treatment with Potential Activity Against Multiple Variants

TFF Pharmaceuticals Advancing Niclosamide, an Inhaled COVID-19 Treatment with Potential Activity Against Multiple Variants

TFF Pharmaceuticals announced it has completed enrollment of 40 healthy subjects in its Phase 1 clinical trial of a dry powder formulation of niclosamide,

trialsitenews.com

TFF Pharmaceuticals announced it has completed enrollment of 40 healthy subjects in its Phase 1 clinical trial of a dry powder formulation of niclosamide, an antiviral treatment with potential to address COVID-19 and other respiratory viral diseases. TFF develops and commercializes products based on its Thin Film Freezing (TFF) platform, which is designed to improve the solubility and absorption of poorly water-soluble drugs. The platform is particularly suitable to generate dry powder particles with properties targeted for inhalation delivery, especially to the deep lung. TFF Pharma intends to share detailed safety data from the Phase 1 study later this quarter.

The Phase 1 trial consisted of a Single Ascending Dose (SAD) and Multiple Ascending Dose (MAD) portion. The SAD phase of the trial consisted of single inhalation doses of 0.5, 2.0, and 6.0 mg in three cohorts of healthy volunteers, including six volunteers who received active drug and two that received placebo, while the MAD phase consisted of doses of 3.0 and 6.0 mg administered twice per day (BID) for 4.5 days (9 total doses). The Safety Management Committee did not raise questions or concerns about safety and recommended the 6.0 mg BID (12 mg total daily dose) as safe for progression into Phase 2 testing.

Per a global licensing agreement, following results from the phase 1 study UNION Therapeutics A/S has an option to exclusively license the dry powder formulation of niclosamide and will be responsible for the next phase of development.

Niclosamide was approved as an oral anthelmintic drug by the U.S. FDA in 1982. It was recently shown to exhibit potent antiviral activity against SARS-CoV-2 but has limited water solubility as well as low absorption and bioavailability when administered orally. TFF Pharmaceuticals intends to utilize its Thin Film Freezing technology to produce an inhaled formulation of niclosamide to target the lungs directly where SARS-CoV-2 infection occurs, avoiding gastrointestinal side effects and overcoming the bioavailability limitations of systemic administration. As niclosamide targets human cell pathways rather than the SARS-CoV-2 virus itself, it is not affected by mutations in the spike protein and could theoretically work against any emerging variant. A preclinical in vivo efficacy study that showed a seven-fold reduction in lung viral load in a hamster model when dry powder niclosamide was administered 24 hours after inoculation with SARS-CoV-2 when the disease was already severe.

A mother's perspective on Bigpharma and instutionalised health culture

Quote from Fm1

External Content youtu.be

Content embedded from external sources will not be displayed without your consent.

Display all external content

Through the activation of external content, you agree that personal data may be transferred to third party platforms. We have provided more information on this in our privacy policy.

Dr. Campbell is a very level thinking person.

His video about data not being released will be decried by the liberal elite as "the majority of the people should not see the data... they are too stupid to interpret it" (We know who here really thinks that!)

It is true, something is afoul and really stinks...

Also, New Zealand... 97 - 99% vaccinated .... and yet forecasting 80,000 cases per day in a 5 million population.... so much for those who say the vaccines would stop this cold if the "damn unvaccinated" would get their jabs.. pandemic of the unvaccinated my ass..

It is this sole, "vaccination only and lockdown approach" that has not only ruined the economy, lives and and perhaps the worst.... brought more division to this world than anything in recent history!

....and "the data should not be released!"

Guess I was right all along.........................................................................................................................................................

Pfizer Tries To Join FDA Lawsuit To Defend Trade Secrets

Pfizer Tries To Join FDA Lawsuit To Defend Trade Secrets

Pfizer told a federal judge in Fort Worth, Texas that the company should be allowed to intervene on behalf of the United States Food and Drug

trialsitenews.com

Pfizer told a federal judge in Fort Worth, Texas that the company should be allowed to intervene on behalf of the United States Food and Drug Administration, which is attempting to delay releasing thousands of documents related to the firm’s experimental mRNA-based COVID-19 vaccine.

Pfizer Wants to Join the FDA in its FOIA Lawsuit Defense

The federal regulatory agency and the pharmaceutical giant asked Texas Northern District Judge Mark Pittman to slow disclosure of most of the requested vaccine documents and to entirely prevent disclosure of others.

Pfizer argued that it had a compelling interest in the case since its proprietary technologies are included in documents Judge Pittman ordered the FDA to turnover. The group demanded that the federal government share all data that factored into the agency’s hasty decision to grant Pfizer’s experimental mRNA vaccine an emergency use authorization – a trove of over 329,000 documents.

One of the documents released so far, entitled “Cumulative Analysis of Post-Authorization Adverse Event Records Reports” revealed that within 90 days of the vaccine’s introduction under the FDA’s emergency use authorization between December 2020 and March 2021, tens of thousands of people reported potential adverse reactions and more than 1,200 deaths were reported.

Judge Rejected the FDA’s Request for 75-Year Delay for Vaccine Records

Pittman’s January 6 ruling rejected the FDA’s proposal to parse out 500-pages-per-month of Pfizer vaccine data over a period of 75 years. Instead, the court ordered the federal agency to produce vaccine data at a rate of 55,000 pages per month.

Pfizer and FDA Want to Withhold Chemistry, Manufacturing and Control Documents

The government and Pfizer have requested that Pfizer’s Chemistry, Manufacturing and Control (CMC) forms, a set of reports that detail analytical methods, validation procedures, and manufacturing processes for the vaccine, be omitted from the public records release.

The FDA and Pfizer lawyers argued that reviewing and redacting trade secrets from among these sensitive papers would be too onerous and would lead to more delays.

The FDA to Federal Court: Release 10,000 Instead of 55,000 Documents-Per-Month

In written pleadings to the court, the FDA requested “that the Court modify its January 6 Order so as to provide that, for the first two 30-day periods following FDA’s scheduled January 31, 2022 production, FDA’s monthly quota be adjusted to 10,000 pages per month,” the FDA said. “Following this initial two-month ‘stand up’ period, the FDA would then be required to process 55,000 pages per month, beginning with its May 2, 2022, production until such time as production is complete.”

Throughout the hearing, the judge noted that despite the divisiveness of the legal case at hand, “we are all Americans and we are all on the same side here.”

Judge Concerned More Delays Will Spawn Fears Of Pfizer Document Shredding

Judge Pittman noted several times his concern that allowing Pfizer to intervene in the case might fuel conspiracy theories of Pfizer and FDA in “some backroom shredding documents.”

He mused that this might undermine the government’s credibility as well as contribute to skepticism about the vaccines. Judge Pittman also said he was concerned that allowing Pfizer to intervene would set a dangerous precedent for a range of other Freedom of Information Act cases.

Pfizer argued that the circumstances of this case were so extreme that no judge would allow it to be used precedent, a sentiment with which the judge seemed to disagree.

Aaron Siri, the attorney for Public Health and Medical Professionals for Transparency, the nonprofit organization of medical professionals and journalists that sued for access to Pfizer vaccine documents, acknowledged that the FDA would likely redact large portions of these documents anyway.

Siri asked why Pfizer perceived a need to intervene after it has already been closely cooperating with the FDA to protect its trade secrets. This has been ongoing since the government approached the firm to develop the vaccines and since the firm first sought emergency use authorization months ago.

As the judge pressed upon the government’s attorneys the need to produce the documents, he also counseled Siri to be cognizant of the difficulty of extracting information from a large federal bureaucracy for which even to “get a tissue box in the restroom” was a tall order.

Judge Pittman noted, however, that in this case, the FDA appeared to be “moving the mountain.”

Vaccine Clinical Trial Data Easy to Release

Apart from the CMC documents, all parties agreed that other documents, including case report forms, which outline clinical trial protocols and results, and the statistical software database related to the vaccine’s development, could be released relatively easily.

Siri argued that Pfizer should help the agency produce the documents but objected to Pfizer intervening in a lawsuit over disclosure of public health agency records and to any further delays of document production.

“Indeed, Pfizer, for over a year now, has been “working closely with the FDA” regarding its Covid-19 vaccine and is already working with the FDA to identify, on or before February 1, 2022, all documents in its application that do not include trade secrets,” Siri argued in his motion. “Nor does Pfizer have any need now to intervene to protect any trade secrets because Plaintiff has not sought to challenge any redactions.”

Siri argued that Pfizer’s intervention was unnecessary and should not cause further delays in producing vaccine data.

“On the other hand, if the Court concludes Pfizer intervening in this action will increase the rate of production beyond what the FDA could do if Pfizer were not granted leave to intervene, and Pfizer’s involvement is limited to prevent delay or prejudice as set forth below, Plaintiff does not object to Pfizer intervening,” Siri said.

In addition to Siri, 15 doctors represented the plaintiffs with specialties such as pediatrics, general surgery, dentistry, family medicine, anesthesiology, rehabilitation medicine, and oncology.

“This is so important even though I had just a few hours notice. I dropped everything. I feel honored to participate in this milestone case,” said Dr. Rebecca Mulholland, a neurologist from Prosper, Texas.

One of The Biggest Public Records Lawsuits in History

According to the recollection of all attorneys present, this case represents the largest and most rapid release of documents under the FOIA.

Hearing Held in Historic Courthouse That Made LBJ, Who Approved FOIA

The sense of history and its consequences was underscored at the outset of the hearing by Judge Pittman, who noted that the hearing was taking place in the very Fort Worth courthouse that the senatorial election fraud case against Lyndon B. Johnson in 1948 was heard.

It was due to that case that Johnson eventually ascended to the vice presidency and, after the assassination of President John F. Kennedy in Houston, the presidency.

Pittman noted that it was President Johnson who had to be dragged “kicking and screaming” to sign the Freedom of Information Act into law.

It was in LBJs presidency that the FOIA was signed into law, but according to Judge Pittman, LBJ had to be dragged “kicking and screaming” to the signing ceremony.

COVID COVER-UP: Pfizer INTERFERES Just Days Before Massive FOIA Vaccine Data Drop, FDA Claims The Vaccine Manufacturer Must Help Review and Redact Documents Before Public Release

COVID COVER-UP: Pfizer INTERFERES Just Days Before Massive FOIA Vaccine Data Drop, FDA Claims The Vaccine Manufacturer Must Help Review and Redact Documents Before Public Release

Who does the US FDA answer to? Well, apparently it’s Pfizer, the German-based Big Pharma megalith. Just days before the FDA was set to release over 12,000…

www.thegatewaypundit.com

Where did Omicron come from? Three key theories

The highly transmissible variant emerged with a host of unusual mutations. Now scientists are trying to work out how it evolved.

Where did Omicron come from? Three key theories

The highly transmissible variant emerged with a host of unusual mutations. Now scientists are trying to work out how it evolved.

www.nature.com

Little more than two months after it was first spotted in South Africa, the Omicron variant of the coronavirus SARS-CoV-2 has spread around the world faster than any previous versions. Scientists have tracked it in more than 120 countries, but remain puzzled by a key question: where did Omicron come from?

There’s no transparent path of transmission linking Omicron to its predecessors. Instead, the variant has an unusual array of mutations, which it evolved entirely outside the view of researchers. Omicron is so different from earlier variants, such as Alpha and Delta, that evolutionary virologists estimate its closest-known genetic ancestor probably dates back to more than a year ago, some time after mid-2020 (ref. 1). “It just came out of nowhere,” says Darren Martin, a computational biologist at the University of Cape Town, South Africa.

The question of Omicron’s origins is of more than academic importance. Working out under what conditions this highly transmissible variant arose might help scientists to understand the risk of new variants emerging, and suggest steps to minimize it, says Angela Rasmussen, a virologist at the University of Saskatchewan Vaccine and Infectious Disease Organization in Saskatoon, Canada. “It’s very difficult to try to mitigate a risk that you can’t even remotely wrap your head around,” she says.

How does Omicron spread so fast? A high viral load isn’t the answer

The World Health Organization’s recently formed Scientific Advisory Group for the Origins of Novel Pathogens (SAGO) met in January to discuss Omicron’s origins. The group is expected to release a report in early February, according to Marietjie Venter, a medical virologist at the University of Pretoria in South Africa, who chairs SAGO.

Ahead of that report, scientists are investigating three theories. Although researchers have sequenced millions of SARS-CoV-2 genomes, they might simply have missed a series of mutations that eventually led to Omicron. Alternatively, the variant might have evolved mutations in one person, as part of a long-term infection. Or it could have emerged unseen in other animal hosts, such as mice or rats.

For now, whichever idea a researcher favours “often comes down to gut feeling rather than any sort of principled argument”, says Richard Neher, a computational biologist at the University of Basel in Switzerland. “They are all fair game,” says Jinal Bhiman, a medical scientist at the National Institute for Communicable Diseases in Johannesburg, South Africa. “Everyone has their favourite hypothesis.”

Craziest genome

Researchers agree that Omicron is a recent arrival. It was first detected in South Africa and Botswana in early November 2021 (see ‘Omicron takeover’); retrospective testing has since found earlier samples from individuals in England on 1 and 3 November, and in South Africa, Nigeria and the United States on 2 November. An analysis of the mutation rate in hundreds of sequenced genomes, and of how quickly the virus had spread through populations by December, dates its emergence to not long before that — around the end of September or early October last year2. In southern Africa, Omicron probably spread from the dense urban province of Gauteng, between Johannesburg and Pretoria, to other provinces and to neighbouring Botswana.

But because Johannesburg is home to the largest airport on the African continent, the variant could have emerged anywhere in the world — merely being picked up in South Africa because of the country’s sophisticated genetic surveillance, says Tulio de Oliveira, a bioinformatician at the University of KwaZulu-Natal in Durban and at Stellenbosch University’s Centre for Epidemic Response and Innovation, who has led South Africa’s efforts to track viral variants, including Omicron.

What stands out about Omicron is its remarkable number of mutations. Martin heard about it when he took a phone call from de Oliveira, who asked him to look at the craziest SARS-CoV-2 genome he had ever seen.

The variant has more than 50 mutations when compared with the original SARS-CoV-2 virus isolated in Wuhan, China (see go.nature.com/32utxva). Some 30 of these contribute to changes in amino acids in the spike protein1, which the coronavirus uses to attach to and fuse with cells. Previous variants of concern have had no more than ten such spike mutations. “That is a hell of a lot of changes,” says Neher (see ‘Most mutated’).

Researchers have seen many of these mutations before. Some were previously known to give the virus an increased ability to bind to the ACE2 receptor protein — which adorns host cells and is the docking point for SARS-CoV-2 — or to help it evade the body’s immune system. Omicron forms a stronger grip on ACE2 than do previously seen variants3. It is also better at evading the virus-blocking ‘neutralizing’ antibodies4 produced by people who have been vaccinated, or who have been infected with earlier variants. Other changes in the spike protein seem to have modified how Omicron enters cells: it appears to be less adept at fusing directly with the cell’s membrane, and instead tends to gain entry after being engulfed in an endosome (a lipid-surrounded bubble)3.

But more than a dozen of Omicron’s mutations are extremely rare: some have not been seen at all before, and others have popped up but disappeared again quickly, presumably because they gave the virus a disadvantage1.

Another curious feature of Omicron is that, from a genomic viewpoint, it consists of three distinct sublineages (called BA.1, BA.2 and BA.3) that all seem to have emerged at around the same time — two of which have taken off globally. That means Omicron had time to diversify before scientists noticed it. Any theory about its origins has to take this feature into account, as well as the number of mutations, notes Joel Wertheim, a molecular epidemiologist at the University of California, San Diego.

Silent spread

Researchers have explained the emergence of previous variants of concern through a simple process of gradual evolution. As SARS-CoV-2 replicates and transmits from person to person, random changes crop up in its RNA sequence, some of which persist. Scientists have observed that, in a given lineage, about one or two single-letter mutations a month make it into the general viral circulation — a mutation rate about half that of influenza. It is also possible for chunks of coronavirus genomes to shuffle and recombine wholesale, adds Kristian Andersen, an infectious-disease researcher at Scripps Research in La Jolla, California. And viruses can evolve faster when there is selection pressure, he says, because mutations are more likely to stick around if they give the virus an increased ability to propagate under certain environmental conditions.

Some scientists think that person-to-person spread would not be conducive to accumulating as many changes as Omicron has since mid-2020. “It does seem like a year and a half is a really short period of time for that many mutations to emerge and to apparently be selected for,” says Rasmussen.

But Bhiman argues that enough time has elapsed. She thinks the mutation process could have occurred unseen, in a region of the world that has limited genomic sequencing and among people who don’t typically get tested, perhaps because they didn’t have symptoms. At some point in the past few months, she says, something happened to help Omicron explode, maybe because the progress of other variants — such as Delta — was gradually impeded by the immunity built up from vaccination and previous infection, whereas Omicron was able to evade this barrier.

Although researchers have submitted almost 7.5 million SARS-CoV-2 sequences to the GISAID genome database, hundreds of millions of viral genomes from people with COVID-19 worldwide have not been sequenced. South Africa, with some 28,000 genomes, has sequenced less than 1% of its known COVID-19 cases, and many nearby countries, from Tanzania to Zimbabwe and Mozambique, have submitted fewer than 1,000 sequences to GISAID (see ‘Missing genomes’).

Martin says that researchers need to sequence SARS-CoV-2 genomes from these countries to get a better sense of the likelihood of unobserved evolution. It is possible that the three sublineages of Omicron each separately arrived in South Africa from a region with limited sequencing capacity, he says.

But de Oliveira says the scenario that Omicron evolved unseen through person-to-person transmission is “extremely implausible”. Intermediate steps in Omicron’s evolution should have been picked up in viral genomes from people travelling from countries that do little sequencing to those that do a lot.

“This is not the nineteenth century, where you take six months to go from point to point by sailboat,” says Sergei Pond, a computational evolutionary biologist at Temple University in Philadelphia, Pennsylvania.

And Andersen adds that, because some of Omicron’s mutations haven’t been seen before, the variant might have evolved in an environment not involving person-to-person chains of transmission. Some of the changes in Omicron don’t match any seen even in the broader viral group of sarbecoviruses, which includes the virus that causes severe acute respiratory syndrome (SARS). For example, one particular site on the genomes of all known sarbecoviruses encodes a serine amino acid, but a mutation in Omicron means the variant has a lysine at that position1, which changes the biochemistry of that region, Andersen says.

However, says Jesse Bloom, a viral evolutionary geneticist at the Fred Hutchinson Cancer Research Center in Seattle, Washington, SARS-CoV-2 has not yet explored all of its possibilities in people. “The virus is still expanding in the evolutionary space.”

Chronic infection

An alternative incubator for fast-paced evolution is a person with a chronic infection. There, the virus can multiply for weeks or months, and different types of mutation can emerge to dodge the body’s immune system. Chronic infections give the virus “the opportunity to play cat and mouse with the immune system”, says Pond, who thinks it is a plausible hypothesis for Omicron’s emergence.

Such chronic infections have been observed in people with compromised immune systems who cannot easily get rid of SARS-CoV-2. For example, a December 2020 case report described a 45-year-old man with a persistent infection5. During almost five months in its host, SARS-CoV-2 accumulated close to a dozen amino-acid changes in its spike protein. Some researchers suggest Alpha emerged in someone with a chronic infection, because, like Omicron, it seems to have accumulated changes at an accelerated rate (see go.nature.com/3yj6kmh).

“The virus has to change to stick around,” says Ben Murrell, an interdisciplinary virologist at the Karolinska Institute in Stockholm. The receptor-binding domain, where many of Omicron’s mutations are concentrated, is an easy target for antibodies, and probably comes under pressure to change in a long-term infection.

But none of the viruses from individuals with chronic infections studied so far has had the scale of mutations observed in Omicron. Achieving that would require high rates of viral replication for a long time, which would presumably make that person very unwell, says Rasmussen. “It seems like a lot of mutations for just one person.”

Further complicating the picture, Omicron’s properties could stem from combinations of mutations working together. For example, two mutations found in Omicron — N501Y together with Q498R — increase a variant’s ability to bind to the ACE2 protein by almost 20 times, according to cell studies6. Preliminary research by Martin and his colleagues suggests that the dozen or so rare mutations in Omicron form three separate clusters, in which they seem to work together to compensate for the negative effects of any single one1.

If this is the case, it means that the virus would have to replicate sufficiently in a person’s body to explore the effects of combinations of mutations — which would take longer to achieve than if it were sampling the space of possible mutations one by one.

One possibility is that multiple individuals with chronic infections were involved, or that Omicron’s ancestor came from someone with a long-term infection and then spent some time in the general population before being detected. “There are a lot of open questions,” says Rasmussen.

Proving this theory is close to impossible, because researchers would need to be lucky enough to find the particular person or group that could have sparked Omicron’s emergence. Still, more comprehensive studies of SARS-CoV-2’s evolution in chronic infections would help to map out the range of possibilities, says Neher.

Mouse or rat

Omicron might not have emerged in a person at all. SARS-CoV-2 is a promiscuous virus: it has spread to a wild leopard, to hyenas and hippopotamuses at zoos, and into pet ferrets and hamsters. It has caused havoc in mink farms across Europe, and has infiltrated populations of white-tailed deer throughout North America. And Omicron might be able to enter a broader selection of animals. Cell-based studies have found that, unlike earlier variants, Omicron’s spike protein can bind to the ACE2 protein of turkeys, chickens and mice3,7.

One study found that the N501Y–Q498R combination of mutations allows variants to bind tightly to rat ACE2 (ref. 6). And Robert Garry, a virologist at Tulane University in New Orleans, Louisiana, notes that several other mutations in Omicron have been seen in SARS-CoV-2 viruses adapting to rodents in laboratory experiments.

‘Killer’ immune cells still recognize Omicron variant

The types of single-nucleotide substitution observed in Omicron’s genome also seem to reflect those typically observed when coronaviruses evolve in mice, and do not match as well with the switches that are observed in coronaviruses adapting to people, according to a study of 45 mutations in Omicron8. The study noted that, in human hosts, G to U substitutions tend to occur in RNA viruses at a higher rate than C to A switches do, but that Omicron does not show this pattern.

It is possible, then, that SARS-CoV-2 could have acquired mutations that gave it access to rats — jumping from an ill person to a rat, possibly through contaminated sewage — and then spread and evolved into Omicron in that animal population. An infected rat could later have come into contact with a person, sparking the emergence of Omicron. The three sublineages of Omicron are sufficiently distinct that, according to this theory, each would represent a separate jump from animal to human.

A large population of animals with infections lasting longer than in humans could give SARS-CoV-2 room to explore a wide diversity of mutations and “build up a large ghost population of viruses that no one knows about”, says Martin, who says he finds this ‘reverse zoonosis’ theory convincing. Changes that make the virus better at spreading in its animal host won’t necessarily affect its ability to infect people, he says.

An animal reservoir could also explain why some of the mutations in Omicron have been rarely seen before in people, says Andersen.

In the dark

But others say that even a single viral jump from an animal to a person is a rare event — let alone three. Meanwhile, the virus has had plenty of opportunities to slip between people. And although some of Omicron’s mutations have been seen in rodents, that doesn’t mean they can’t happen or haven’t occurred in people, too, and have simply been missed.

Murrell also points out that SARS-CoV-2 didn’t immediately go through a period of accelerated evolution after jumping to people for the first time. When it spread to mink and deer, it did pick up changes, but not as many mutations as Omicron has accumulated, says Spyros Lytras, an evolutionary virologist at the University of Glasgow, UK. This means that the evidence isn’t sufficient to suggest Omicron’s predecessor would have undergone rapid selection after finding a new home in the wild.

To confirm this theory, researchers would need to find close relatives of Omicron in another animal, but they haven’t been looking — “something that has been horribly neglected”, says Martin. Since the pandemic began, researchers have sequenced fewer than 2,000 SARS-CoV-2 genomes isolated from other animals, mostly from mink, cats and deer.

Now that Omicron has taken off, how it evolves in people could offer more clues about its origins. It might, for instance, shed mutations that, in retrospect, are found to have helped it adapt to a different animal host, or in a person with a chronic infection. But it could also not change by much, leaving researchers in the dark.

The answer to Omicron’s emergence will probably be one or a combination of the three scenarios, says Bloom. But, he adds, researchers are far from explaining the processes that brought Omicron here, let alone predicting what the next variant will look like.

And many scientists say they might never find out where Omicron came from. “Omicron really shows us the need for humility in thinking about our ability to understand the processes that are shaping the evolution of viruses like SARS-CoV-2,” says Bloom.

Nature 602, 26-28 (2022)

Selection analysis identifies significant mutational changes in Omicron that are likely to influence both antibody neutralization and Spike function (Part 1 of 2)

Selection analysis identifies significant mutational changes in Omicron that are likely to influence both antibody neutralization and Spike function (part 1 of…

virological.org

doi: https://doi.org/10.1038/d41586-022-00215-2

References

1.

Martin, D. P. et al. Preprint at bioRxiv https://doi.org/10.1101/2022.01.14.476382 (2022).

2.

Viana, R. et al. Nature https://doi.org/10.1038/s41586-022-04411-y (2022).

PubMed

Article

Google Scholar

3.

Peacock, T. P. et al. Preprint at bioRxiv https://doi.org/10.1101/2021.12.31.474653 (2022).

4.

Cele, S. et al. Preprint at medRxiv https://doi.org/10.1101/2021.12.08.21267417 (2021).

5.

Choi, B. et al. N. Engl. J. Med. 383, 2291–2293 (2020).

PubMed

Article

Google Scholar

6.

Bate, N. et al. Preprint at bioRxiv https://doi.org/10.1101/2021.12.23.473975 (2021).

7.

Cameroni, E. et al. Preprint at bioRxiv https://doi.org/10.1101/2021.12.12.472269 (2021).

8.

Wei, C. et al. J. Genet. Genom. 48, 1111–1121 (2021).

Mink to humans, rats to humans and hamsters to human, Houston we have a problem

Transmission of SARS-CoV-2 (Variant Delta) from Pet Hamsters to Humans and Onward Human Propagation of the Adapted Strain: A Case Study

Hong Kong study shows hamster-to-human Covid-19 spread: Lancet

Hong Kong study shows hamster-to-human Covid-19 spread: Lancet

It is the first documented evidence of hamster-to-human transmission of the Delta variant. . Read more at straitstimes.com.

www.straitstimes.com

HONG KONG (BLOOMBERG) - Hong Kong researchers have found evidence that pet hamsters can spread Covid-19 to people, and linked the animals to human infections in the city.

The study, published on Saturday (Jan 29) in The Lancet as a preprint and not yet peer-reviewed, provided the first documented evidence of hamster-to-human transmission of the Delta variant.

Researchers from the University of Hong Kong and the city's government found two independent cases of such transmission, after testing viral swabs and blood samples from animals collected from local pet shops.

The hamsters in question were infected around Nov 21, before they were imported to Hong Kong, suggesting pet animal trade may be a pathway that facilitates Covid-19 to spread across borders, according to the study.

"This study reveals that pet hamsters can acquire Sars-CoV-2 infection in real-life settings and can transmit the virus back to humans," the researchers said in the study.

"The Sars-CoV-2 circulating in hamsters can allow sustainable virus transmission in humans

It advised members of the public earlier this month to surrender hamsters purchased on or after Dec 22 for "humane dispatch", after some pet store workers and customers tested positive for the virus, and some of the animals imported from the Netherlands at the store tested preliminary positive.