Posts by Fm1

Awake prone positioning for COVID-19 acute hypoxaemic respiratory failure: a randomised, controlled, multinational, open-label meta-trial

DEFINE_ME

Summary

Background

Awake prone positioning has been reported to improve oxygenation for patients with COVID-19 in retrospective and observational studies, but whether it improves patient-centred outcomes is unknown. We aimed to evaluate the efficacy of awake prone positioning to prevent intubation or death in patients with severe COVID-19 in a large-scale randomised trial.

Methods

In this prospective, a priori set up and defined, collaborative meta-trial of six randomised controlled open-label superiority trials, adults who required respiratory support with high-flow nasal cannula for acute hypoxaemic respiratory failure due to COVID-19 were randomly assigned to awake prone positioning or standard care. Hospitals from six countries were involved: Canada, France, Ireland, Mexico, USA, Spain. Patients or their care providers were not masked to allocated treatment. The primary composite outcome was treatment failure, defined as the proportion of patients intubated or dying within 28 days of enrolment. The six trials are registered with ClinicalTrials.gov, NCT04325906, NCT04347941, NCT04358939, NCT04395144, NCT04391140, and NCT04477655.

Findings

Between April 2, 2020 and Jan 26, 2021, 1126 patients were enrolled and randomly assigned to awake prone positioning (n=567) or standard care (n=559). 1121 patients (excluding five who withdrew from the study) were included in the intention-to-treat analysis. Treatment failure occurred in 223 (40%) of 564 patients assigned to awake prone positioning and in 257 (46%) of 557 patients assigned to standard care (relative risk 0·86 [95% CI 0·75−0·98]). The hazard ratio (HR) for intubation was 0·75 (0·62−0·91), and the HR for mortality was 0·87 (0·68−1·11) with awake prone positioning compared with standard care within 28 days of enrolment. The incidence of prespecified adverse events was low and similar in both groups.

Interpretation

Awake prone positioning of patients with hypoxaemic respiratory failure due to COVID-19 reduces the incidence of treatment failure and the need for intubation without any signal of harm. These results support routine awake prone positioning of patients with COVID-19 who require support with high-flow nasal cannula

26 of the 27 Scientists Dismissing Lab-Leak Theory Have Ties to Wuhan Institute of Virology

The UK’s Daily Telegraph recently investigated the resurgent controversy as to the origin of the COVID-19 pandemic. Two predominant explanations include 1) natural cause—that is some zoonotic animal-to-animal-to-human transmission or 2) the lab-leak theory. Early on, experts in the National Institutes of Health (NIH) cautioned Dr. Anthony Fauci that aspects of the new pathogen looked lab engineered. A frantic set of meetings occurred, and a unified message emanated thereafter—that the disease came from a natural zoonotic process like the last two coronaviruses. Yet concern was there from the start that the proximity of the Wuhan Institute of Virology to the wet market where the pandemic supposedly started. Despite such suspicions, however, 27 prominent scientists wrote a letter published in the influential “The Lancet” medical journal unilaterally dismissing the lab-leak theory as did Fauci and the NIH leadership apparatus. From then on, any mention of lab leak theory on social media led to immediate censorship evidencing early on in the pandemic coordination between government and private technology companies such as Facebook, Google, and Twitter. Of course, most recently, the specter of a lab leak became a prominent discussion, and in fact, President Joe Biden ordered an investigation into the matter. Now thanks to the Daily Telegraph probe, it turns out that of the 27 scientists that collaborated on the letter outright dismissing any possibility that COVID-19 originated from the Wuhan Institute of Virology, 26 of them actually have substantial links to Chinese researchers, colleagues or its benefactors at the Wuhan-based lab.

In a report by Sarah Knapton, UK’s Daily Telegraph details the intimate and intricate ties these scientists have to the Wuhan Institute of Virology. One of the more notable signatories to The Lancet letter included Dr. Peter Daszak, the president of EcoHealth Alliance and beneficiary of NIH funds that were channeled to the Wuhan-based lab at a time that gain-of-function research was banned in America.

But was Daszak involved with gain-of-function research? TrialSite reported that a recent document dump at The Intercept indicates that gain-of-function research was possibly going on and that Dr. Anthony Fauci was aware of such research, thus implicating the honesty of his recent testimony in front of Congress categorically denying that any gain-of-function research was occurring. Fauci and backers would propose that these probes are purely political in nature.

Follow the link to review the entire list of scientists covered by The Daily Telegraph investigation.

What is the Evidence

Thus far, no one in China has come forward to prove the natural origin hypothesis and by May 14 in Science, a group of 18 experts penned that “we must take hypothesis about both natural and laboratory spillovers seriously until we have sufficient data.”

While another study obtained by the Daily Mail in May led by Angus Dalgleish of the UK and Dr. Birger Sorensen of Norway declared they had a ‘prima facie evidence of retro-engineering in China for a year.”

Their study suggests Chinese destroyed, concealed, or withheld data indicating a cover-up. In January, the World Health Organization sent a team to Wuhan to investigate the origins of COVID-19 further.

Interestingly Dr. Peter Daszak led WHO’s American representation, which seems odd at best and raises the prospect of a possible conflict of interest.

The trip wasn’t that helpful, and in fact, WHO’s director-general Dr. Tedros Adhanom Ghebreyesus, implied the Chinese authorities hadn’t cooperated fully. Lately, jingoistic propaganda in China implies SARS-CoV-2 originates in possibly a U.S. military laboratory.

Check TrialSite’s “Origin of COVID-19” for a timeline of events that could indicate a possible lab connection to the pathogen. However, no one is certain as to the truth.

But assuming the Daily Telegraph’s assessment is correct, that the 26 scientists that were so adamant as to the nonsensical lab leak theory actually have material ties to the Wuhan lab, one’s mind can easily wander into conspiratorial land.

https://www.telegraph.co.uk/news/2021/09/10/revealed-scientists-dismissed-wuhan-lab-theory-linked-chinese/

The US is nearing immunity from COVID-19

The US is nearing immunity from COVID-19

The numbers of COVID-19 cases, new hospitalizations, and deaths nationwide peaked and started to decline around the beginning of September.

nypost.com

Despite media claims that “We Can’t Turn the Corner on COVID,” the numbers of COVID-19 cases, new hospitalizations, and deaths nationwide peaked and started to decline around the beginning of September. The combination of this milestone, new findings from the Centers for Disease Control and Prevention showing widespread levels of vaccination and natural immunity, and improved availability of treatments suggests that, outside of isolated pockets, COVID-19 is likely to become a diminishing health risk in the United States.

The CDC looked for evidence of prior infection or vaccination in the blood of approximately 1.5 million blood donors from around the country between July 2020 and May 2021. Based on the antibodies found in the specimens, they were able to distinguish between those who had been vaccinated and those with antibodies resulting from infection. As of the end of May, the combined vaccine and infection seroprevalence (indicating the proportion of the population with antibodies and some level of immune protection) was 83 percent for those 16 and older (children under 16 can’t donate blood). Over 20 percent had antibodies indicating an earlier infection and recovery. Based on the infection-induced seroprevalence, the researchers estimated that there were actually 2.1 infections per reported COVID-19 case.

Now, following the surge from the Delta variant, the number of confirmed COVID-19 cases (all ages) is over 40 million, or 8 million more than on May 31. Applying the 2.1 multiple from the blood donation study to the entire population results in a real number of cases and people with natural immunity of 84 million, or 25 percent of the population.

In addition, 177 million people are fully vaccinated, which is 53 percent of the total population and 34 million more than at the end of May. An additional 10 percent of the population has received a single dose, which provides some protection, albeit less than the full two doses.

While there is overlap because some previously infected people have been vaccinated, roughly 80 percent of the country has vaccine or natural immunity. Both types of immunity provide effective protection against COVID-19. The risk of breakthrough infections among the vaccinated is small, and when they occur, the vaccines continue to be effective in preventing serious illness, even for the Delta variant. The CDC also acknowledges that reinfection of recovered COVID-19 patients is rare.

Though a few vaccines induce a better immune response than natural infection, experts generally say that “natural infection almost always causes better immunity than vaccines.” This appears to be true with ­COVID-19.

A new study from Israel confirms that natural immunity to COVID-19 is superior to vaccine-induced immunity, even with the Delta variant. Between June 1 and August 14, when Delta was dominant in Israel, the risk of infections was 13 times higher for vaccinated people than for previously infected, unvaccinated people when either the infection or vaccination had occurred between four and seven months before. The risk for symptomatic breakthrough infections was 27-fold higher. While natural immunity did wane somewhat over time, vaccinated persons still had a six-fold higher risk for infection and a seven-fold higher risk for symptomatic illness than people infected up to ten months before vaccinations started.

An earlier study at the Cleveland Clinic of more than 52,000 health-care workers from December 16, 2020 to May 15, 2021 (just before Delta became dominant in the United States) found that both natural immunity and vaccine immunity provide good protection against infections. Not one of the 1,359 previously infected subjects who remained unvaccinated was reinfected. Their risk of infection was no higher than for vaccinated people, whether they were previously infected or uninfected.

Moreover, natural immunity thus far appears to be at least as long-lasting as vaccine immunity. Even before vaccines were widely available, studies indicated that four types of immune memory persist for more than six months after infection. The Cleveland Clinic results suggested that natural immunity provides protection against reinfection for ten or more months, leading the authors to conclude that previously infected COVID-19 patients are “unlikely to benefit” from vaccination. Another study found that convalescent individuals maintained immunologic protection for 12 months without vaccination, though protection could be enhanced by vaccination.

COVID-19 treatments have improved as well. Several versions of monoclonal antibodies have been authorized and are now readily available. These medicines are highly effective at keeping early COVID-19 from progressing, thus decreasing the risk of hospitalization or death by 70 percent to 85 percent, particularly for people at high risk of developing severe disease. Steroids and new, more effective ICU protocols have also led to lower COVID-19 mortality.

Of course, some super variant that escapes vaccine and natural immunity and is resistant to treatments could emerge, much as the emergence of Delta upset many forecasts. There is no way to predict such developments. But even the highly contagious Delta variant, which raised estimates of the percentages needed for herd immunity, did not evade vaccine and natural immunity protection. Delta morbidity and mortality has been heavily concentrated among those who had neither vaccine nor natural immunity.

Ending the COVID-19 pandemic doesn’t mean that the virus will be eradicated or that there will be no new cases. It means that serious illness and death resulting from infection with a virus that has likely become endemic will become rare. Our innovative, free-market economy has provided new vaccines and therapies in record time. Thanks to that, and to the undersold but important phenomenon of natural immunity, we are most of the way there.

Joel Zinberg, M.D., J.D., is a senior fellow at the Competitive Enterprise Institute and an associate clinical professor of surgery at the Icahn Mount Sinai School of Medicine in New York.

UK Walks Away from Lockdowns & Vaccine Passports in Abrupt Turnaround—Harbinger of More to Come in West

UK Walks Away from Lockdowns & Vaccine Passports in Abrupt Turnaround—Harbinger of More to Come in West

In an abrupt turnaround and perhaps a harbinger of more news to come, vaccine passports will be chucked as a means to tightly manage English society under

trialsitenews.com

In an abrupt turnaround and perhaps a harbinger of more news to come, vaccine passports will be chucked as a means to tightly manage English society under the guise of public health. Reported recently by Reuters, UK’s Secretary of State for Health and Social Care, Sajid Javid recently declared to multiple news outlets, including the BBC that “We shouldn’t be doing things for the sake of it.” As the plan’s enactment was just around the corner, apparently enough resistance and criticism from the political classes influenced the changing position.

A scheme meant to be on reserve, meaning ready for implementation should another COVID-19 surge manifest in the cold forthcoming months, this plan would have required residents to produce proof of vaccination—determining if fully vaccinated or just one jab or a COVID-19 test result or demonstration of completing the necessary quarantine period should any show that they were recently infected.

Happy with the change are the various entertainment and cultural sectors in England, particularly in London and the other mid-sized UK cities. Apparently, political resistance among Tory MPs participating in the conservative-leaning COVID Recovery Group in addition to Liberal Democrats coalesced into a powerful enough coalition to overturn the decision. Ed Davey, leader of the latter-based group, was quoted in the BBC that vaccine passports were “divisive, unworkable and expensive.”

A major turnaround given the UK Vaccines Minister Nadhim Zahawi declared the end of September as the time to activate the new strict public health-inspired laws for at least the duration of the pandemic. Zahawi rationalized that this vaccine passport would be the best way to ensure the return of what’s known as the “night industry.”

No More Lockdowns

Health secretary Javid also announced that he was “not anticipating” any more lockdowns although establishing that they may be needed at some point if surges manifest declaring that it would be “irresponsible to take everything off the table.”

Conflict over 12-15 year old Vaccinations?

While TrialSite reported that the Joint Committee on Vaccination and Immunization (JCVI) recommended against vaccinating healthy 12-to-15-year-old, ultimately, the Chief Medical Officers have the final say. According to secretary Javid, the government gears up the vaccine administration apparatus for that cohort should the light be green.

Growing Protests

TrialSite shares with the community that a growing number of “medical freedom” protests occur in Europe’s major cities, Brazil, Canada, and others places. While the mainstream media barely covers the rapidly growing crowds, that doesn’t mean they are not gaining momentum; which they appear to be doing. TrialSite is working on an original piece tracking the medical freedom movement.

End the pandemic, ivermectin and a cartoon of kools !

Drugs that mimic effects of cigarette smoke reduce SARS-CoV-2's ability to enter cells

Drugs that mimic effects of cigarette smoke reduce SARS-CoV-2's ability to enter cells

Researchers have identified a potential reason why lower numbers of COVID cases have appeared amongst smokers compared to non-smokers, even as other reports…

medicalxpress.com

Researchers have identified a potential reason why lower numbers of COVID cases have appeared amongst smokers compared to non-smokers, even as other reports suggest smoking increases severity of the disease.

Researchers have identified two drugs that mimic the effect of chemicals in cigarette smoke to bind to a receptor in mammalian cells that inhibits production of ACE2 proteins, a process that appears to reduce the ability of the SARS-CoV-2 virus to enter the cell.

The findings appear in the journal Scientific Reports on 17 August.

Something of a paradox exists with respect to smoking cigarettes and COVID-19. Active smoking is associated with increased severity of disease, but at the same time, many reports have suggested lower numbers of COVID cases amongst smokers than amongst non-smokers.

"Something strange was going on here," said Keiji Tanimoto of Hiroshima University's Research Institute for Radiation Biology and Medicine, the corresponding author of the paper. "But we had a few ideas about how to tease out what some of the mechanisms at work might be."

"We must stress the presence of strong evidence showing that smoking increases the severity of COVID-19," Tanimoto added. "But the mechanism we discovered here is worth further investigation as a potential tool to fight SARS-CoV-2 infections."

It is known that cigarette smoke contains polycyclic aromatic hydrocarbons (PAHs). These can bind to and activate aryl hydrocarbon receptors (AHRs). A receptor is any structure of the surface or inside of a cell that is shaped to receive and bind to a particular substance. AHRs are a type of receptor inside of mammalian cells that is in turn a transcription factor—something that can induce a wide range of cellular activities through its ability to increase or decrease the expression of certain genes.

Knowing this about the relationship between PAHs and AHRs, the researchers wanted to investigate the effect of drugs that activate AHR on expression of the genes that control production of the ACE2 protein—the infamous receptor protein on the surface of many cells types that works like a lock that the SARS-CoV-2 virus is able to pick. After binding the virus to the ACE2 protein, it can then enter and infect the cell.

First, the scientists investigated various cell lines to examine their gene expression levels of ACE2. They found that those cells originating in the oral cavity, lungs and liver had the highest ACE2 expression.

These high-ACE2-expression cells were then subjected to various doses of cigarette-smoke extract (CSE) for 24 hours. After this, the rate of expression of the CYP1A1 gene, which is known to be inducible by CSE, was evaluated. The CSE treatment had induced increased expression of CYP1A1 gene in liver and lung cells in a dose-dependent manner—the greater the dose, the greater the effect. However, this effect was not as pronounced in oral cavity cells. In other words, greater activity of the CYP1A1, less production of the ACE2 receptors—the route that the virus is able to enter cells.

In order to explain why this was happening in the presence of cigarette smoke, the researchers then used RNA sequencing analysis to investigate what was happening with gene expression more comprehensively. They found that CSE increased the expressions of genes related to a number of key signaling processes within the cell that are regulated by AHR.

To more directly observe this mechanism by which AHR acts on ACE2 expression, the effects of two drugs that can activate AHR were evaluated on the liver cells. The first, 6‑formylindolo(3,2‑b)carbazole (FICZ) is derivative of the amino acid tryptophan, and the second, omeprazole (OMP), is a medication already widely used in the treatment of acid reflux and peptic ulcers.

RNA sequencing data suggested that the CYP1A1 gene was strongly induced in liver cells by these AHR activators, and expression of the ACE2 gene was strongly inhibited, again in a dose-dependent manner.

In other words, the cigarette smoke extract and these two drugs—all of which act as activators of AHR—are able to suppress the expression of ACE2 in mammalian cells, and by doing so, reduce the ability of the SARS-CoV-2 virus to enter the cell.

Based on the findings in the lab, the team is now proceeding with pre-clinical and clinical trials on the drugs as a novel anti-COVID-19 therapy.

Mixed Data From the UK as Vaccines Show Positive Impact Yet Specter of Breakthrough infections Grows

Mixed Data From the UK as Vaccines Show Positive Impact Yet Specter of Breakthrough infections Grows

TrialSite recently shared that the influential UK Joint Committee on Vaccination and Immunization (JCVI) declared that there is no need at this point to

trialsitenews.com

TrialSite recently shared that the influential UK Joint Committee on Vaccination and Immunization (JCVI) declared that there is no need at this point to vaccinate healthy children ages 12 to 15 for COVID-19. Articulating that sound vaccination policy balancing risks and benefits doesn’t merit such a broad-based move at this point in time, now Public Health England’s most recent report titled “COVID-19 Vaccine Surveillance report Week 36” indicates that while the vaccines continue to work well unvaccinated kids face a lower risk of COVID-19 death than fully vaccinated adults of any age. Some studies indicate major benefits of the vaccine in reducing hospitalization and death, while other data indicate a growing number of breakthrough infections, including hospitalization. The UK appears to be headed down a different path than America however, in strategy, taking a more targeted approach.

Benefits to England

According to the PHE report after several studies, the vaccines continue to be quite effective, with one dose offering between 55 and 70% effectiveness against symptomatic disease, while more severe progression of disease is mitigated. Moreover, PHE declares there is some indication based on a “number of studies” that the vaccines can help reduce viral spread.

PHE furthermore estimates that the vaccine program has helped the nation avoid 143,600 hospitalizations, possibly preventing 24.4 to 24.9 million infections and importantly, between 108,600 to 116,200 deaths

Headed toward Herd Immunity?

PHE also reports that based on a representative sampling of antibody testing of blood donors that 97.7% of the adult population now have the antibodies to COVID-19 from either SARS-CoV-2 infection or vaccination as compared to 18.1% that have antibodies via only infection. Put another way, 95% of the adults aged 17 and up now have antibodies from either infection or vaccination.

Why the Spike

TrialSite suggests some of the existing data may need further explaining. For example, the UK is one of the most vaccinated major nations on the planet. Nearly 66% of the entire population is fully immunized, while almost 73% have received at least one dose.

Yet, a major surge in cases occurred over the past few months. Starting in early June, a delta variant-driven spike in cases represented a third major spike in the pandemic here. By May 2021, however, the average daily case rate hovered around 2,000 new cases per day, far below the numbers in the previous spike in cases from September 2020 to February 2021.

By July 17th, the UK reported 53,969 cases all the while mass vaccination commenced. The cases did dip in much of July yet have gone back up in August and into September, with 37,691 new cases as the 7-day average by Friday, September 10th.

Deaths are also up, although nowhere near what they were before, evidenced by a combination of not only vaccines but also treatments (monoclonal antibodies, dexamethasone, etc. are in use in the health system and are working). From April through much of June, the average daily death count due to COVID-19 was significantly low, ranging anywhere from 5 to 15 per day in this nation of 68.3 million people.

However, the death count has risen despite a heavily vaccinated population, now at 135 per day based on the 7-day average, substantially up from the spring and early summer. The majority of deaths are still among the unvaccinated, but importantly the viral transmission can originate from the vaccinated person.

A recent real-world study led by Anglo-American academic medical centers published in The Lancet indicates lower breakthrough infection rates. The prospective, community-based, nested case-control study was based on self-reported data and had a number of limitations. But nonetheless, the study team led by Kings College London in the UK found that the targeting of vaccines to at-risk populations is key to boost vaccine effectiveness as well as infection control measures.

As breakthrough infections are seriously present the authors declare “Our findings might support caution around relaxing physical distancing and other personal protective measures in the post-vaccination era..”

Mainstream publications such as Forbes have reported that although breakthrough infections most often don’t lead to more serious illness, they, in fact, do. In one week, 40% of confirmed patients with the delta variant-based infection were ultimately admitted to the hospital yet had at least one dose of the vaccine.

Call to Action: TrialSite will continue to monitor the situation in heavily vaccinated nations, including Israel and the UK

Biden Completely Ignores Natural Immunity as if the Science is All Settled

Biden Completely Ignores Natural Immunity as if the Science is All Settled

At least some physicians are mustering the courage to speak truth to the powers that be after the POTUS speech Friday, essentially introducing

trialsitenews.com

At least some physicians are mustering the courage to speak truth to the powers that be after the POTUS speech Friday, essentially introducing unprecedented federal reach into the private sector via OSHA regulations. All businesses with 100 employees or more must mandate COVID-19 vaccines or onerous weekly testing. But what about natural immunity? What if individuals recently had COVID-19? Some data shows that this immunity is superior to that of the vaccines. Despite the fact that a large percentage of the adult population is already vaccinated and/or been infected with SARS-CoV-2 and countries such as the UK and Israel take into account natural immunity, Biden “paid no attention to the role of natural immunity” reports Dr. Jeffrey Singer to ABC News’ Jan Jeffcoat.

Studies

Singer references, “Numerous studies now are showing that people who’ve had previous COVID-19 infections are their immunity is either equal to or maybe even greater than vaccine-induced immunity.

TrialSite reported on one Israeli study that demonstrated natural COVID-19 immunity was far superior to Pfizer’s mRNA vaccine immunity for fighting off the delta variant, for example.

One of the nation’s large HMOs, Maccabi Healthcare Services and Tel Aviv University, School of Public Health recently shared study results indicating bombshell results. Their research suggests that natural immune protection that develops post a COVID-19 infection generates materially more protection against the Delta variant than the two-dose Pfizer-BioNTech vaccine. In fact, some observers of the study labeled it as the “don’t try this at home” approach.

Of course, the study has limitations and is yet to be peer-reviewed, so it can’t be used as fully weighted evidence, but nonetheless, this and other studies indicate the seriousness of natural immunity.

What is the POTUS Agenda?

But why isn’t POTUS taking this important variable seriously? Why force whole segments of the population to submit to a vaccine when they may even have stronger protection than the vaccine itself, assuming they were infected in the past half-year.

As reported by ABC, “Numerous experts are having a debate, some think that people with a previous COVID infection don’t need to get vaccinated, some think they just need the first of the two mRNA doses, but apparently, according to President Biden, the science is settled,” said Dr. Singer.

Biden didn’t bother to think about the millions of people who have been infected already, and whose natural immunity now protects them in many cases, when during the speech, he started at the camera, leaning toward the viewer, and whispering, “our patience is wearing thing” continuing with a specific message to the 100 million unvaccinated “how much more information do you need, what are you waiting for.” Such an intrusive and some might consider unacceptably degrading tone may actually create more problems for POTUS.

Israeli Study Reveals Natural SARS-2-CoV-2 Immunity Far Superior to Pfizer’s mRNA Vaccine for Fighting Off Delta Variant

Israeli Study Reveals Natural SARS-2-CoV-2 Immunity Far Superior to Pfizer’s mRNA Vaccine for Fighting Off Delta Variant

Israeli researchers affiliated with Maccabi Healthcare Services and Tel Aviv University, School of Public Health, uploaded a yet-to-be-reviewed study

trialsitenews.com

Grotesque conflicts of interest on NIH ivermectin non-recommendation

Grotesque conflicts of interest on NIH ivermectin non-recommendation

Note that views expressed in this opinion article are the writer’s personal views and not necessarily those of TrialSite. This article is currently FREE

trialsitenews.com

Note that views expressed in this opinion article are the writer’s personal views and not necessarily those of TrialSite. This article is currently FREE to read and share without paying.

The National Institutes of Health provided a non-recommendation for the use of ivermectin in COVID-19, stating that there was:

“insufficient evidence … to recommend either for or against the use of ivermectin for the treatment of COVID-19.”

The process for reaching that non-recommendation, however, is opaque. The Panel members responsible for therapy recommendations are disclosed and also that:

“… working groups propose updates to the Guidelines based on the latest published research findings and evolving clinical information.”

However, NIH has gone to extreme efforts to avoid stating whether a vote was held to endorse the ivermectin non-recommendation. This includes fighting a Freedom of Information Act request in federal court. A deceptive non-vote would constitute an atrocity. NIH has also been secretive about the composition of the working group that proposed the ivermectin non-recommendation. The names of those individuals were redacted by the NIH from a document obtained through a Freedom of Information Act request for the agenda of a meeting considering ivermectin.

However, the group responsible for the ivermectin non-recommendation has been discovered through a FOIA request to the Center for Disease Control and Prevention. The FOIA response shows that the working group has nine members. Three members of the working group, Adaora Adimora, Roger Bedimo, and David V. Glidden, have disclosed a financial relationship with Merck. Merck has campaigned against the use of ivermectin in COVID-19. A fourth member, Susanna Naggie, had an extraordinary potential conflict of interest. She received a $155 million grant for the study of ivermectin following the non-recommendation. Funding for the study would have been difficult to justify if the drug was recommended for use in COVID-19. It is not known, however, if the panelist was aware of that opportunity or was planning to apply for that grant at the time of the deliberations on ivermectin.

The deception and secrecy surrounding the NIH ivermectin non-recommendation should have raised serious doubts about its integrity. The grotesque conflicts of interest of Panel members should make it clear that the NIH, as the FDA with its slandering of ivermectin as a “horse dewormer,” should not be taken seriously

Quote from Wyttenbach

https://swprs.org/severe-covid…-viral-autoimmune-attack/

What happens in severe CoV-19 and under what only condition HCQ can help.

Already in 2020, multiple studies indicated that severe covid is not just a viral pneumonia, but might be a so-called anti-phospholipid antibody syndrome (APS), i.e. an autoimmune attack against phospholipids in endothelial cells causing hypercoagulation, thrombosis, and respiratory failure.

I posted a lot of info a year ago pointing to this being a bradykinin immune response

Mixed Data From the UK as Vaccines Show Positive Impact Yet Specter of Breakthrough infections Grows

Mixed Data From the UK as Vaccines Show Positive Impact Yet Specter of Breakthrough infections Grows

TrialSite recently shared that the influential UK Joint Committee on Vaccination and Immunization (JCVI) declared that there is no need at this point to

trialsitenews.com

TrialSite recently shared that the influential UK Joint Committee on Vaccination and Immunization (JCVI) declared that there is no need at this point to vaccinate healthy children ages 12 to 15 for COVID-19. Articulating that sound vaccination policy balancing risks and benefits doesn’t merit such a broad-based move at this point in time, now Public Health England’s most recent report titled “COVID-19 Vaccine Surveillance report Week 36” indicates that while the vaccines continue to work well unvaccinated kids face a lower risk of COVID-19 death than fully vaccinated adults of any age. Some studies indicate major benefits of the vaccine in reducing hospitalization and death, while other data indicate a growing number of breakthrough infections, including hospitalization. The UK appears to be headed down a different path than America however, in strategy, taking a more targeted approach.

Benefits to England

According to the PHE report after several studies, the vaccines continue to be quite effective, with one dose offering between 55 and 70% effectiveness against symptomatic disease, while more severe progression of disease is mitigated. Moreover, PHE declares there is some indication based on a “number of studies” that the vaccines can help reduce viral spread.

PHE furthermore estimates that the vaccine program has helped the nation avoid 143,600 hospitalizations, possibly preventing 24.4 to 24.9 million infections and importantly, between 108,600 to 116,200 deaths

Headed toward Herd Immunity?

PHE also reports that based on a representative sampling of antibody testing of blood donors that 97.7% of the adult population now have the antibodies to COVID-19 from either SARS-CoV-2 infection or vaccination as compared to 18.1% that have antibodies via only infection. Put another way, 95% of the adults aged 17 and up now have antibodies from either infection or vaccination.

Why the Spike

TrialSite suggests some of the existing data may need further explaining. For example, the UK is one of the most vaccinated major nations on the planet. Nearly 66% of the entire population is fully immunized, while almost 73% have received at least one dose.

Yet, a major surge in cases occurred over the past few months. Starting in early June, a delta variant-driven spike in cases represented a third major spike in the pandemic here. By May 2021, however, the average daily case rate hovered around 2,000 new cases per day, far below the numbers in the previous spike in cases from September 2020 to February 2021.

By July 17th, the UK reported 53,969 cases all the while mass vaccination commenced. The cases did dip in much of July yet have gone back up in August and into September, with 37,691 new cases as the 7-day average by Friday, September 10th.

Deaths are also up, although nowhere near what they were before, evidenced by a combination of not only vaccines but also treatments (monoclonal antibodies, dexamethasone, etc. are in use in the health system and are working). From April through much of June, the average daily death count due to COVID-19 was significantly low, ranging anywhere from 5 to 15 per day in this nation of 68.3 million people.

However, the death count has risen despite a heavily vaccinated population, now at 135 per day based on the 7-day average, substantially up from the spring and early summer. The majority of deaths are still among the unvaccinated, but importantly the viral transmission can originate from the vaccinated person.

A recent real-world study led by Anglo-American academic medical centers published in The Lancet indicates lower breakthrough infection rates. The prospective, community-based, nested case-control study was based on self-reported data and had a number of limitations. But nonetheless, the study team led by Kings College London in the UK found that the targeting of vaccines to at-risk populations is key to boost vaccine effectiveness as well as infection control measures.

As breakthrough infections are seriously present the authors declare “Our findings might support caution around relaxing physical distancing and other personal protective measures in the post-vaccination era..”

Mainstream publications such as Forbes have reported that although breakthrough infections most often don’t lead to more serious illness, they, in fact, do. In one week, 40% of confirmed patients with the delta variant-based infection were ultimately admitted to the hospital yet had at least one dose of the vaccine.

Call to Action: TrialSite will continue to monitor the situation in heavily vaccinated nations, including Israel and the UK.

Quote from THHuxleynew

No. TrialSite spend a lot of its time publishing opinionated and biassed editorials.

As does the international media

Australia’s TGA Bans GPs from Prescribing Ivermectin—Cites Interruption with Vaccination as Clear Factor

Australia’s TGA Bans GPs from Prescribing Ivermectin—Cites Interruption with Vaccination as Clear Factor

Australia’s medicine and therapeutic regulatory, the Therapeutic Good Administration (TGA) recently took the gloves off with Ivermectin, the economical

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CoV-2, the virus behind COVID-19. Now TGA formally places a national prohibition on off-label prescribing of ivermectin to all general practitioners. A comparable move as to what TGA did with hydroxychloroquine in 2020. Clearly further evidence of tightening encroachment of the critically important doctor-patient treatment relationship allowing consent to medical treatment using off-label medications. Of course, this isn’t occurring in a vacuum—it’s part of an unfolding, integrated and what have the signs of a coordinated and orchestrated government action to stop any and all treatments other than those the government declares acceptable.

Background

The new restrictions are based on the inputs of the Advisory Committee for Medicines Scheduling (ACMS), an advisory group that makes recommendations to the Secretary Department of Health. Since 2010 this executive branch function has sole decision making authority, superseding that power from the National Drugs and Poisons Schedule Committee (NDPSC).

The new restrictions materially impact what general practitioners and specialists can do with their patients. Now via national regulatory edict, general practitioners (GP) can only prescribe ivermectin for TGA—approved conditions or what is known as indications. In this case, that means scabies and certain parasitic conditions. This is the case even if the GP has consulted with specialists and believes the treatment is the most appropriate for the patient. A stunning move that in normal times would have physician associations’ attention.

While select specialists may be able to access the drug, the proclamation carves out the potential opportunity for infectious disease physicians, dermatologists, gastroenterologists, and hepatologists (liver disease specialists) to prescribe off label to the patient if they deem such decision appropriate for the particular patient, the rule will overnight dramatically reduce the number of prescriptions.

And even for the exemptions, new policies, procedures and practices will encumber even these specialists in their ability to practice medicine. The costs associated with applying, registering and complying will deter most from such a pathway.

Overall Rationale for Decision

According to the TGA, this decision came about “because of concerns with the prescribing of oral ivermectin for the claimed prevention or treatment of COVID-19.”The regulator’s logic rests on the premise that ivermectin isn’t approved by Australia or any other “developed” countries and thus its “use is by the general public for COVID-19 is currently strongly discouraged by the National COVID Clinical Evidence Taskforce, the World Health Organization and the U.S. Food and Drug Administration (FDA).

What are the Declared Risks Supporting the Decision?

The regulatory body cites three (3) risk factors driving their decision, including 1) interruption of vaccination program 2) higher dosage (e.g., implied safety risk) and 3) dramatic increase in prescriptions—all three above of which represent a threat to public health.

In a refreshingly clear manner, TGA firstly indicates the use of ivermectin off-label threatens the mass vaccination program. For much of the pandemic, Australia kept cases out of the country with strict border controls and stern measures on mobility, including lockdowns and the like. However, with the highly transmissible delta, the government went into full throttle a vaccine-centric strategy similar to that in America. From this vantage, the risks of the pandemic nationwide are mitigated only first and foremost by universal vaccination.

With substantial vaccine hesitancy in the country, the Australian government took the vaccine-centric mandate into overdrive starting in the early summer. Since then, vaccination rates have rapidly climbed (as of Sep 9–53% at least one dose and 32.6% fully vaccinated) marked by notable events such as the inoculation of 20,000 high school kids at the nation’s largest stadium.

The way TGA views the world, if people believe they are protected from infection by taking another drug prescribed by their GP, then they may opt to avoid the jab. In their own words, “Individuals who believe that they are protected from infection by taking ivermectin may choose not to get tested or to seek medical care if they experience symptoms. Doing so has the potential to spread the risk of COVID-19 infection throughout the community.”

While TGA cites concerns of social media and “other” sources influencing the public, the proclamation indicates that ivermectin doses used off-label for COVID-19 are higher than the current indication, thus implicating safety concerns. Based on this logic, Australia’s GPs are not equipped to know the difference hence are now banned from prescribing this drug off label. Yet, of course, specialists may apply for an exemption—but everything will be controlled and monitored much like controlled substances (e.g., opiates are managed).

Finally, with such huge demand comes what are declared to be local shortages of ivermectin for its current intended use. This could have an adverse impact on what they consider legitimate uses. When combining these three factors in the context of the overall rational, TGA issued the rule.

Who Supplies the Country & For What Indication?

The only TGA-approved oral ivermectin product is Merck’s Stromectol Ivermectin 3mg tablet blister pack, indicated for the treatment of river blindness (onchocerciasis) threadworm of the intestines (intestinal strongyloidiasis) and scabies. Merck has been active in lobbying its interests here.

The TrialSite community is aware that Merck is in a frantic race to own the COVID-19 antiviral market, next to Pfizer and Roche via a partnership with Atea Pharmaceuticals. At stake is what TrialSite estimates is a large market, anywhere from a few billion per year to several billion worldwide, maybe more. That’s because over 90% of COVID-19 cases are mild-to-moderate, requiring isolation, bed rest and time. Any antiviral that compresses that time, reduces symptoms and importantly lowers the probability of disease progression makes a profound impact on the pandemic.

In addition to rumblings that Merck is cautioning national governments about ivermectin, TrialSite reported they have smartly inked deals in low-and middle-income countries (LMICs), including multiple production and distribution deals in India.

In fact, it is with one of those Indian licensors of the product that has led to a deal in Vietnam, as reported by TrialSite. Indian suppliers to that country shipped the investigational product to public health authorities that are using the experimental drug in a real-world setting: a pilot public health home care program in Ho Chi Minh City. An unorthodox situation—this isn’t a study but rather, an actual medical care setting via the public health agency for the largest city in the nation. This raises important ethical concerns, including conflict of interest and informed consent principles.

Conclusion

Now a regulatory electric fence exists between general practice doctors on the one hand, and on the other, what they can prescribe to their patients. Cross that line and the GP has violated a federal rule, risking civil penalties and a loss of a license. While a carve out an exemption for specialists exists undoubtedly more top-down national controls reinforce the overall effect on the power, or lack thereof, of physicians generally.

Some in Australia question the ethical practice of the ACMS and its determination of what medical care is available to the Australian public. As mentioned previously since 2010, the Secretary Department of Health is empowered with sole decision making authority based on ACMS inputs.

What happens next? What about thousands of people in Australia that may have what were perfectly legal off-label prescriptions for ivermectin? Have these doctors now violated the regulatory rule? What happens to the patient—are they just cut off? What if the regimen is working well? Will legal challenges ensue?

Based on this national command, it appears unlikely that the government will take a flexible, negotiation friendly stance with health care professionals. Thus, a trend that appears present around the developed world—centralizing tendencies with national health, in this case here in Australia—indicates an erosion of private choice to access medical treatment.

TrialSite, dedicated to transparent, accessible, and open research worldwide, exists to chronicle, analyze, and publish unbiased, objective news and information. Ultimately health is the most important personal security and without correct information, individuals cannot make the most informed decisions.

Thus with no attachment to ivermectin, TrialSite simply tracked the various studies around the world that indicated positive results. Intrigued, we interviewed many dozens of physicians and scientists, part of the quest to better understand the unfolding situation. The TrialSite fact sheet provides what we believe is one of the more unbiased perspectives at least up until this writing.

TrialSite has reported the government health agencies in America, coupled with medical societies now circle the ivermectin proponent wagon and similar formal edicts may be coming soon.

Quote from THHuxleynew

If you want to win hearts and minds you do not call the vaccine-hesitant anti-vaxers, do not have policies that force them to get vaccinated, but engage with their fears, which need to be taken seriously, and explain the facts.

As used here anti-vaxer applies to a small number of activists who spread propaganda and will never (until dying of COVID as in http://sorryantivaxxer.com) change views. I'd be similarly against obese people trying to make everyone else obese.

Similarly if you want to reduce obesity it does not help to shame those who are obese or insult them. In that case changing things is a lot more difficult, but encouragement and advice can help, and changes in the relative cost and availability of healthy and unhealthy food could make obesity less likely. Good luck doing that without massive (probably not fit for purpose) regulation.

At the moment if you are very poor in the UK the only way to get enough food to survive quickly (e.g. without cooking skills many now don't have, and prep time most now don't have) is to eat very unhealthy food and cut out vegetables.

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Agreed but I'm confused, do you support mandates, this sounds like you don't.

Quote from THHuxleynew

One of the things people do not always do is process probabilities well.

Sure, obesity is a risk factor - but 30% extra COVID risk is equivalent to being 2 years older.

I'm pretty sure this covers all age groups so I think your 2 year older would rise exponentially with age. Either way obisity is a huge problem in America promoted under political policy, McDonald's and other fast food bring in big taxes. This is why the NIH, the CDC and FDA can no longer be part of government. Political appointees follow the administration, not always the science! Just look at American elementary schools, a good portion are already over weight and suffer from one or more chronic illness. Obesity is one of the leading reasons for our 37th ranked healthcare system and yet we promote it as being healthy. You can shame an anti Vaxer but call someone a fat piece of shit and you are a racist. Confusion RULES!!!!!!!!!!!

Dem Rx is bad medicine – and Joe Biden knows it

Dem Rx is bad medicine – and Joe Biden knows it

President Joe Biden’s overly aggressive approach at nixing the Constitution to push absurd laws proves the Republicans care about America more than he does.

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President Biden’s chief of staff, Ron Klain, gave up the administration’s game by endorsing a tweet from MSNBC’s Stephanie Ruhle:

“OSHA doing this vaxx mandate as an emergency workplace safety rule is the ultimate work-around for the Federal govt to require vaccinations.”

So as with other things — such as the federal eviction moratorium — Biden knows his actions are unconstitutional. He’ll just try to do it anyway with loopholes and gambles that by the time the case winds its way through the courts, it won’t matter.

It’s all so performative and cynical.

Biden isn’t playing to the unvaccinated, who are even less likely to get the shot after being lectured to and insulted by the president.

It’s for smug Democrats who appreciate him lecturing and insulting those people, dividing the nation even more.

Biden could have tried compassion and empathy instead of anger and hectoring. Instead, after his mismanagement of everything from the border to the economy, Biden is trying to lay claim to some moral high ground. Look at those GOP governors, they are “cavalier” with life, he claimed Friday

Biden could have tried compassion and empathy instead of anger and hectoring. Instead, after his mismanagement of everything from the border to the economy, Biden is trying to lay claim to some moral high ground. Look at those GOP governors, they are “cavalier” with life, he claimed Friday

Not as cavalier as Biden was with the 13 service members who died as a result of the president’s disastrous Afghanistan withdrawal, or how cavalier he’s being with the American lives he’s left behind there.

Nor as cavalier as Biden is with his own beliefs: In the last year he has both cast doubt over the efficacy of vaccines (because Trump was still in charge) and vowed he doesn’t believe in vaccine mandates, then reversed himself on both.

But these GOP governors and other opponents of Biden’s dubious mandates do care — about the higher principles the president would trample over.

The vaccine orders are just the latest Democratic Party maneuver to federalize our lives, the Constitution be damned. Election law, abortion, education — all must be dictated by a tiny Democratic majority in Washington, and if that fails, well, there are “work-arounds.”

The Post has campaigned for vaccinations. They work. They are getting us back to normal, even as Democratic governors and mayors keep trying to move the goalposts.

But high-handed contempt for 80 million Americans, while violating laws and norms, is not the answer. Democrats wonder why Biden’s approval rating is plummeting, and 69 percent of those polled say things are going badly in the country. This is why.

Boys more at risk from Pfizer jab side-effect than Covid, suggests study

Boys more at risk from Pfizer jab side-effect than Covid, suggests study | Coronavirus | The Guardian

Healthy boys may be more likely to be admitted to hospital with a rare side-effect of the Pfizer/BioNTech Covid vaccine that causes inflammation of the heart than with Covid itself, US researchers claim.

Their analysis of medical data suggests that boys aged 12 to 15, with no underlying medical conditions, are four to six times more likely to be diagnosed with vaccine-related myocarditis than ending up in hospital with Covid over a four-month period.

Most children who experienced the rare side-effect had symptoms within days of the second shot of Pfizer/BioNTech vaccine, though a similar side-effect is seen with the Moderna jab. About 86% of the boys affected required some hospital care, the authors said.

Saul Faust, professor of paediatric immunology and infectious diseases at the University of Southampton, who was not involved in the work, said the findings appeared to justify the cautious approach taken on teenage vaccines by the UK’s Joint Committee on Vaccines and Immunisation.

The JCVI did not recommend vaccinating healthy 12 to 15-year-olds, but referred the matter to the UK’s chief medical officers who are expected to make a final decision next week. Children aged 12 to 15 who are particularly vulnerable to Covid, or who live with an at-risk person, are eligible for the shots.

In the latest study, which has yet to be peer reviewed, Dr Tracy Høeg at the University of California and colleagues analysed adverse reactions to Covid vaccines in US children aged 12 to 17 during the first six months of 2021. They estimate the rate of myocarditis after two shots of Pfizer/BioNTech vaccine to be 162.2 cases per million for healthy boys aged 12 to 15 and 94 cases per million for healthy boys aged 16 to 17. The equivalent rates for girls were 13.4 and 13 cases per million, respectively. At current US infection rates, the risk of a healthy adolescent being taken to hospital with Covid in the next 120 days is about 44 per million, they said.

How reliable the data is and whether similar numbers could be seen in the UK if healthy 12 to 15-year-olds are vaccinated are unclear: vaccine reactions are recorded differently in the US and shots are given at longer time intervals in the UK. According to the UK medicines regulator, the rate of myocarditis after Covid vaccination is only six per million shots of Pfizer/BioNTech.

So far, UK children have not been admitted to hospital for Covid in large numbers and may not be at great risk of long Covid. While the recent Clock study found that up to 14% of children who caught Covid may still have symptoms 15 weeks later, levels of fatigue appear similar to those in children who have not caught the virus. This suggests that children may be spared some of the most debilitating problems seen in adult long Covid.

The overwhelming majority of myocarditis appears after the second dose of vaccine, so offering single shots could protect children while reducing their risk of the side effect even further.

“While myocarditis after vaccination is exceptionally rare, we may be able to change the first or second doses or combine vaccines differently to avoid the risk at all, once we understand the physiology better,” said Prof Faust. “On balance, there is no urgency to immunise children from a medical perspective, although if schools are unable to maintain education for the vast majority at all times, the overall balance could shift. If my two teenage children are offered the vaccine by the NHS my GP wife and I will have no hesitation in allowing them to receive the vaccine.”

Prof Adam Finn, a member of JCVI at the University of Bristol, said: “I stand by the JCVI advice, which is not to go ahead at this time with vaccinating healthy 12 to 15-year-olds on health outcome risk-benefit grounds given the current uncertainty – as there is a small but plausible risk that rare harms could turn out to outweigh modest benefits.”

The Smoking Syringe: Was evidence withheld from ACIP when they recommended the Pfizer-Vaccine?

The Smoking Syringe: Was evidence withheld from ACIP when they recommended the Pfizer-Vaccine?

Opinion Editorial by: David Wiseman Ph.D., M.R.Pharm.S. Summary On Monday, August 30, 2021, the Advisory Committee on Immunization Practices (ACIP) voted

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Opinion Editorial by: David Wiseman Ph.D., M.R.Pharm.S.

Summary

On Monday, August 30, 2021, the Advisory Committee on Immunization Practices (ACIP) voted unanimously to approve a recommendation that stated:

The Pfizer-BioNTech Covid-19 vaccine is recommended for people 16 years of age and older under FDA’s Biologics License Application (BLA) approval

This recommendation was quickly endorsed by CDC Director, Dr. Rochelle Walensky.

In approving this recommendation, ACIP heard evidence from Pfizer, Kaiser Permanente, CDC, and other scientists on the safety and effectiveness of the vaccine.

Apparently fully or partially absent from this evidence were six studies, cited in a post-vote presentation. These studies, including those by CDC and Pfizer scientists, describe waning vaccine effectiveness, or effectiveness against the delta strain, from the 90-95% range to, in one case to as low as 42%.

The inclusion of these missing studies would have yielded a different risk-benefit analysis.

Given the ramifications this recommendation is already having on vaccine mandate policy, the evidence presented to ACIP does not appear to meet the highest level of standards for scientific integrity and conduct.

Other intense safety signals, such as a 177 times increase in the number of deaths per vaccinated person reported for Covid-19 vaccines, compared with flu vaccines, were not considered.

ACIP did not consider the possible effects of the vaccines on pregnancy or the reproductive system, hinted at by the announcement the same day by NIH, to fund studies on the links between the Covid-19 vaccines and menstrual disorders.

ACIP did not consider other possible long-term effects (cancer, autoimmune disease) of the vaccines related to their falling under the FDA classification of a “gene therapy product,” and made no comment about the lack of studies performed by Pfizer/BioNTech “for the potential to cause carcinogenicity, genotoxicity, or impairment of male fertility.”

The significant short and potentially long-term cardiac, vascular, hematological, musculoskeletal, intestinal, respiratory or neurologic symptoms health issues stemming from the use of these vaccines pose a major and expensive public health problem.To concretize recognition of, and to spur action to avert and confront this potential public health crisis, we have proposed the term:

Post Covid Vaccine Syndrome – pCoVS

There needs to be:

Assignment of ICD10 and related tracking or reimbursement codes for pCoVS.

Funding for research and tracking for long-term and delayed pCoVS.

Regulation of the Pfizer, Moderna, and Janssen vaccines as Gene Therapy products, requiring long-term follow-up.

Since FDA and CDC cannot assure us about the safety of two vaccine doses, how can they give any assurance about a third (or more doses)?

Introduction

On Monday, August 30, 2021, the Advisory Committee on Immunization Practices (ACIP) voted unanimously to approve a recommendation that stated:

The Pfizer-BioNTech Covid-19 vaccine is recommended for people 16 years of age and older under FDA’s Biologics License Application (BLA) approval

Shortly thereafter, Dr. Rochelle Walensky, Director of the Centers for Disease Control and Prevention (CDC), endorsed this recommendation,[1] adding “We now have a fully approved COVID-19 vaccine and ACIP has added its recommendation. If you have been waiting for this approval before getting the vaccine, now is the time to get vaccinated and join the more than 173 million Americans who are already fully vaccinated,”

Once the recommendation is published in CDC’s Morbidity and Mortality Weekly Report (MMWR), this statement will “represent the official CDC recommendations for immunizations in the United States.”[2]

Within the fine print of the evidence presented to ACIP prior to its vote, are details that suggest that the vote may have been influenced by possible scientific misconduct.

What happened? Who was voting and why?

Unlike FDA, whose mission is to ensure that medical products can only be marketed if they are safe and effective, CDC[3] “conducts critical science and provides health information that protects our nation…” Advising the CDC are specialist and expert committees such as the Advisory Committee on Immunization Practices (ACIP) composed of non-government scientists, doctors, health professionals, and community representatives.

ACIP was asked by CDC to formulate a recommendation regarding the use of the Pfizer-BioNTech vaccine. To inform ACIP’s decision, scientists and doctors from Pfizer BioNTech and CDC provided evidence concerning the vaccine’s safety and effectiveness as well as a risk-benefit analysis.

I along with colleagues, submitted pre- and post-meeting comments,(1,2) some of which are included in this article.

How safe is the Pfizer-BioNTech vaccine?

The safety discussion drew from several of the systems used to monitor vaccine safety shown on slide 4 from the presentation of Dr. Grace Lee, the chairperson of ACIP.

Focus on myocarditis

The safety discussion focused on myocarditis (inflammation of the heart muscle), particularly in younger subjects. One CDC presentation[4] cited a study published in NEJM (3) reporting a 3 times higher risk of myocarditis associated with Pfizer-BioNTech vaccination, compared with an 18 times higher risk associated with SARS-CoV-2 infection. In other words, a 18/3 = 6 times greater risk of myocarditis if you get Covid-19 than if you have the vaccine. This figure of 6 agreed with a non-peer-reviewed preprint study looking at mRNA vaccines(4) (two other CDC studies showing higher numbers were cited, but these studies have not been published – remember that – and only available to CDC internally). This is a six-fold increase IF contracting Covid. What the presentation did not say is that this is canceled out by the (at best) 1 in 8 chance of getting Covid-19 in the first place!

Slide 9 from presentation by Dr. Rosenblum (footnote 4)

Deaths and myocardial infarctions missing from safety discussion

What else was not mentioned? In written comments my colleagues and I (1) submitted to ACIP prior to the meeting, we compared the number of reports in VAERS for either death or myocardial infarction (heart attack) associated with the Covid-19 and flu vaccines. Adjusting for the number of doses given. There were 91 times more deaths and 126 times more heart attacks for the Covid-19 vaccines compared with the flu vaccines. If adjusted by the number of people receiving at least one dose, the figure for deaths is about 177 (July 30 figures).

This does not PROVE that the vaccines were the cause of these events. But that’s not the point. This is called a signal. It is a very intense one and awaits a transparent explanation[5] that includes a comprehensive report of the types and numbers of investigations performed, including autopsies. Although CDC has provided guidance for the conduct of autopsies of Covid-19 cases, there is no prospective protocol for the conduct of autopsies to determine whether or not the death is vaccine-related. This would include a detailed description of the types of histopathological methods to distinguish vaccine-induced spike protein from spike protein derived from a Covid-19 infection. Where is this analysis? Where is there a protocol? Similarly, the strong signal of heart attacks in younger than in older people (403 vs. 88, Table 1) must be investigated.

In our submitted comments,(1) we identified three separate pools of vaccine-associated deaths, totaling 45,000-147,000 deaths that should be viewed in the context of the upper estimate of 140,000 lives saved due to the vaccines (to May 2021).(5)

Non Covid-19 deaths under-reported in VAERS – 20,400-62,500

Covid-19 deaths in vaccinated subjects – 25,000-85,000

An unknown number of deaths in non-vaccinated contributed by transmission from vaccinated people.

It is important to distinguish between these three pools, as each may have separate sets of causes. In the first pool early, non-Covid-related deaths may be related to the toxicity of the spike protein towards heart cells and effects on coagulation. Covid-related deaths may have resulted from post-vaccination immune suppression, possibly hinted at by a 40% -vaccine-associated increase in Herpes zoster infections reported in a large Israeli study(3) and referenced in one of the CDC presentations to ACIP.[6] Covid-19 may have been unwittingly transmitted by vaccinees to the non-vaccinated(6,7), including by fecal aerosol(8) in subjects sharing bathrooms.

The Precautionary Principle places the burden of proof on CDC to convincingly rule out an association between these events and the Covid-19 vaccines.

Table 1: Signals of deaths or myocardial infarctions reported in VAERS for COVID-19 vaccines compared with Flu Vaccines

Ages Deaths Myocardial Infarction

10-17 32 n.e.

18-49 64 403

50-64 85 121

65+ 98 88

All 10+ 91 126

The number shown is the ratio of the number of VAERS reports (per dose) for the Covid-19 vaccines in comparison with the Flu vaccines (2015/16-2019/20 flu seasons) for each age group. Covid-19 reporting rates include all reports to VAERS for COVID-19 vaccines as of Aug. 6, 2021. n.e not estimable. Excerpted from (1).

Critics of these sorts of analyses have claimed there may have been overreporting related to enhanced reporting requirements pursuant to Emergency Use Authorization.[7] A number of the CDC presentations referenced data from VAERS without expressing any such concern. Indeed, the point was made in one presentation, that for myocarditis/ pericarditis at least, the VAERS and VSD (Vaccine Safety Datalink[8]) incidence data, agreed closely.

This similarity was not sufficient to generate a safety signal (age unstratified) for myocarditis[9] within the VSD system which uses a signal detection method called Rapid Cycle Analysis (RCA). Although in theory, RCA should be able to detect signals in near real-time as medical records are being generated in a system such as Kaiser Permanente, the method appears even less sensitive than the methods prescribed for VAERS(9) which themselves have known limitations.(1) From VAERS, myocarditis is acknowledged to be an issue as a warning in the COMIRNATY package insert attests: (10)

“Postmarketing data demonstrate increased risks of myocarditis and pericarditis, particularly within 7 days following the second dose.”

A paper was published in JAMA (11) on September 3rd describing the findings from the Rapid Cycle Analysis of the VSD system. It concluded that:

“incidence of selected serious outcomes was not significantly higher 1 to 21 days postvaccination compared with 22 to 42 days postvaccination.”

I suggest that publication of this paper without the context of the acknowledged myocarditis signals from VAERS, within the conclusion, is highly misleading.

Long term harms missing from safety discussion: gene therapy products, cancer

Also missing from the discussion were potential long-term effects of these vaccines, given that they also meet FDA’s definition for Gene Therapy products. .(12) Indeed, in 2020 Moderna acknowledged(13) that ”Currently, mRNA is considered a gene therapy product by the FDA.” Why is this important? Because FDA, is (appropriately) concerned for the effects of the gene therapy product on malignant (cancer), neurologic, autoimmune, hematologic, or other disorders. The concern is so great that FDA may require follow-up evaluations of study patients for between 5 and 15 years. When did FDA decide to ignore its own guidance document? (12) [10]

The package insert(10) for the vaccine that was approved by the FDA on August 23rd states that “COMIRNATY has not been evaluated for the potential to cause carcinogenicity, genotoxicity, or impairment of male fertility.” Neither in the BLA Approval letter,(14) nor in the Summary Basis for Regulatory Approval(15) is there a POST MARKETING REQUIREMENT to conduct studies on carcinogenicity, genotoxicity, or male fertility.

Effects on reproductive system missing from safety discussion: menstrual disorders

What else was missing? On the very same day, CDC staff were providing evidence to ACIP on the safety of the Pfizer vaccine, NIH made the startling announcement[11] that it was funding studies “to explore potential links between COVID-19 vaccination and menstrual changes.” They elaborated: “Some women have reported experiencing irregular or missing menstrual periods, bleeding that is heavier than usual, and other menstrual changes after receiving COVID-19 vaccines.” Was CDC not aware of this?

But the operative word here is “Some.” A query in VAERS (9/3/21) for various menstrual disorders[12] revealed that for reports associated with the Covid-19 vaccines, “some” means.

7037 separate menstrual disorder-related symptoms were described in 4783 unique reports.

Some? By comparison with all other vaccines, for ALL years COMBINED we have 897 symptoms in 798 unique events. Most of these are accounted for by the HPV vaccines (698 symptoms in 623 events) with seasonal flu vaccines contributing only 47 symptoms within 45 unique events.

Having worked extensively in the area of women’s health for most of my career,[13] I reluctantly confess that this was not on my radar screen. Concerns had been raised from animal studies showing the distribution of some vaccine components to the ovaries. Some menstrual effects were picked up in another analysis.(16) However, I know that “menstrual disorders” are far too often trivialized. A number of these disorders lead to early hysterectomies triggering further complications including adhesions, pain, bowel obstruction, heart disease, and dementia. Will these sorts of problems be considered in risk-benefit analyses?

NIH illustrates a number of reasons for these reported menstrual changes. No doubt out of an intense desire to be transparent with the American public in disclosing ALL of the possible reasons for these menstrual changes, NIH included in their list “pandemic-related stress.” But stress is not our prime suspect. Effects on the ovaries and uterus are, and we must view these reported menstrual changes in the context of unresolved questions about the safety of the vaccines on the reproductive system in general, and on pregnancy in particular.

Preliminary findings of a CDC study(17) published in June involving 35,691 pregnant v-safe surveillance system participants and 3958 participants enrolled in the v-safe pregnancy registry (only 827 of whom had a completed pregnancy), “did not show obvious safety signals among pregnant persons who received mRNA Covid-19 vaccines.” The study acknowledged that “more longitudinal follow-up, including follow-up of large numbers of women vaccinated earlier in pregnancy, is necessary to inform maternal, pregnancy, and infant outcomes.”

The results of a follow-up report from this CDC study,(17) appeared in NEJM on September 8th (18), and were surely known at the time of the ACIP meeting. With the startling absence of a randomized control group, the report concluded that:

“our findings suggest that the risk of spontaneous abortion after mRNA Covid-19 vaccination either before conception or during pregnancy is consistent with the expected risk of spontaneous abortion; these findings add to the accumulating evidence about the safety of mRNA Covid-19 vaccination in pregnancy”

In my opinion, this conclusion overreaches to the point of recklessness as it conflicts with and downplays the guidance provided in the COMIRNATY package insert(10) under a subheading “Risk Summary”:

“Available data on COMIRNATY administered to pregnant women are insufficient to inform vaccine-associated risks in pregnancy.”

Not that the package insert, overall is much better at providing clear guidance for pregnancy. It states: “There is a pregnancy exposure registry for COMIRNATY. Encourage individuals exposed to COMIRNATY around the time of conception or during pregnancy to register by visiting https://mothertobaby.org/ongoingstudy/covid19-vaccines/.”

As stated in their approval letter,(14) the best the FDA has done to determine what sorts of risks are posed during pregnancy is to obtain the commitment from BioNTech to conduct a post-marketing pregnancy/neonatal study with a four-year term.

Study C4591022, entitled “Pfizer-BioNTech COVID-19 Vaccine Exposure during Pregnancy: A Non-Interventional Post-Approval Safety Study of Pregnancy and Infant Outcomes in the Organization of Teratology Information Specialists (OTIS)/MotherToBaby Pregnancy Registry.”

Note the word commitment. As FDA explains[14]

“Postmarketing commitments (PMCs) are studies or clinical trials that a sponsor has agreed to conduct, but that are not required by a statute or regulation.”

This is not a requirement (as for some of the other post-marketing studies on myocarditis for example). Compare not only this level of regulation but also the length and scope of the study in question with an unrelated Janssen (J&J) biologic product for which a 7-year[15] study is required and which includes examining effects on child and early development. A recently approved (2021) Astra-Zeneca biologic product[16] requires a NINE-year study on pregnancy and maternal and fetal/neonatal outcomes.

Inadequate risk-benefit analysis

None of this featured in the evidence CDC gave to ACIP. Indeed, the only harm of any note in the risk-benefit analysis (itself focusing on 16–29-year-olds) was myocarditis.[17]

Slide 16 from presentation by Dr. Rosenblum (footnote 4)

post-Covid Vaccine Syndrome

The sheer number of deaths or other events reported in VAERS for the Covid-19 vaccines (similar to all deaths or events reported for all other vaccines in all years combined) cannot be ignored. The significant short and potentially long-term health issues stemming from the use of these vaccines pose a major and expensive public health problem.To concretize recognition of, and to spur action to avert and confront this potential public health crisis, we have proposed the term:

Post Covid Vaccine Syndrome – pCoVS

defined as:

A syndrome occurring after injection of antigen-inducing, gene therapy vaccines to SARS-Cov-2 virus. The syndrome is currently understood to manifest variously as cardiac, vascular, hematological, musculoskeletal, intestinal, respiratory or neurologic symptoms of unknown long-term significance, in addition to effects on gestation. Manifestations of the syndrome may be mediated by the spike protein antigen induced by the delivered nucleic acids, the nucleic acids themselves, or vaccine adjuvants. As more data become available, subsets and longer-term consequences of pCoVS may become apparent, requiring revision of this definition.

We(1) have proposed:

Recognition by public health agencies, governments, and professional societies of pCoVS.

Assignment of ICD10 and related tracking or reimbursement codes for pCoVS.

Establishment of transparent systems to monitor and track for long-term and delayed pCoVS.

Establishment of funding for research into the prevention and treatment of pCoVS.

Regulation of the Pfizer, Moderna, and Janssen vaccines as Gene Therapy products.

Insistence on long-term (15 years) pharmacovigilance by manufacturers of these vaccines for pCoVS consistent with FDA guidelines for gene therapy products.

Legislation to prevent discrimination based on vaccination[18] or actual or potential pCoVS status.

Establishment of funding to determine what effects the gene therapy vaccines have on the genome or gene expression.

How effective is the Pfizer BioNTech Vaccine

Inclusion of outdated, non-RCT, observational and non-peer-reviewed studies

Contributing significantly to the analysis by several presenters of safety and efficacy, as well as the risk-benefit analysis for the Pfizer vaccine was Pfizer’s own RCT of about 40,000 subjects[19] which was recently released as a non-peer-reviewed pre-print.(19) It was widely recognized throughout the discussion that these data only reported safety and effectiveness data for up to six months of the Pfizer vaccine, for data collected up to March 13 2021. Does Pfizer have data collected after March 13?

The use of observational or non-peer-reviewed (preprinted) studies by proponents of re-purposed drugs has been heavily criticized by public health officials as well as the media, who have insisted on evidence from large peer-reviewed RCTs. It was with some wonder that observational and non-peer-reviewed studies were included in one of the key analyses (slide 19)[20] provided to support ACIP’s recommendation, 17 observational studies, including 7 non-peer-reviewed, were employed. During the discussion, the presenter (Dr. Gargano) concurred with one of the discussants that there was good agreement between data from observational and RCT sources. Only one RCT was included19 with reference to additional about-to-be published (NEJM) study (remember that).[21]

Of these 17 studies, one reported data with mixed variants, one with the delta variant only, two with the alpha and delta variant and only one with the Delta variant. During this discussion, which preceded ACIP’s vote on recommending the Pfizer vaccine, there was no consideration of the effects of the delta variant or of waning immunity described in a post-vote presentation.[22]

Why were data describing waning immunity or effectiveness against delta omitted prior to the vote?

Get out your magnifying glass and look at the small print for slide 6.

Slide 6 from presentation by Dr. Gargano (footnote 15)

“Articles were eligible for inclusion if published before 8/20/21”

This sounds perfectly reasonable except when you look at the evidence presented (footnote 14) in a discussion of booster doses, waning immunity, and the Delta variant that took place AFTER ACIP voted to recommend the Pfizer vaccine.

Slide 15 of Dr. Oliver’s presentation shows a waning of vaccine effectiveness to between 40 and 80%.

Slide 15 from presentation of Dr. Oliver (footnote 14)

Why was this waning effectiveness not considered PRIOR to the vote being taken? Surely any recommendation to use the vaccine must take into account prevailing levels of efficacy, regardless of how good it was before? You will answer by saying that CDC needed time to complete their pre-vote analysis, so they had a cutoff date of August 20. Let’s take a look at the four studies shown on this slide.

Nanduri et al. (20) This was a CDC paper showing loss of VE from 74.7% to 53.1% in nursing home residents. The paper was published in CDC’s own journal MMWR (Morbidity and Mortality Weekly Report) on August 27. It was not included in the pre-vote evidence for effectiveness because it did not meet the August 20 cut-off. But we saw earlier how unpublished data (including CDC data) had been incorporated into the pre-vote analysis. There is one more problem here. The Nanduri paper states: “On August 18, 2021, this report was posted as an MMWR Early Release on the MMWR website,” thus meeting the cut-off criteria.

Rosenberg et al., (21) This is another CDC report showing a decline in vaccine effectiveness against infection for New York adults from 91.7% to 79.8%. It was published in MMWR on August 27, with an early release date of August 18.

Puranik et al. (22) This non-peer-reviewed preprint showed a decline to July 2021 in the effectiveness of the Moderna vaccine to 76% and the Pfizer vaccine to 42%. This paper was not authored by CDC staff and was first posted on medrxiv August 8, with revisions posted on August 9 and 21. These revisions showed the same declining effectiveness. This study WAS referenced in the pre-vote presentation by Dr. Gargano (footnote 16), however, the finding of 42% effectiveness against infection does not appear to have been tabulated.

Fowlkes et al. (23) Another CDC paper showed waning immunity from 91% to 66% in front-line workers. This was published in MMWR on August 27, but with an early release date of August 24. Why this was not released on August 18, along with the Nanduri paper is unclear. Another paper by CDC and other authors (24) which showed sustained effectiveness in adults was included in the pre-vote analysis and was published on August 27 in MMWR with an early release date of August 18.

Slide 52 of the same presentation contained a list of 14 references for recent estimates of vaccine effectiveness against the Delta variant, including the four papers cited above.

Slide 52 from presentation of Dr. Oliver footnote 14

There were three other papers in this list that also described waning immunity or reduced immunity of the Pfizer vaccine against the Delta variant.

#10. Sheikh et al. (25) The paper itself states that it was published online on June 14, 2021, and stated “Both the Oxford–AstraZeneca and Pfizer–BioNTech COVID-19 vaccines were effective in reducing the risk of SARS-CoV-2 infection and COVID-19 hospitalization in people with the Delta VOC, but these effects on infection appeared to be diminished when compared to those with the Alpha VOC.”

#13. Tartof et al. (26) This study results were:

“For fully vaccinated individuals, effectiveness against SARS-CoV-2 infections was 73% (95%CI: 72‒74) and against COVID-19-related hospitalizations was 90% (89‒92). Effectiveness against infections declined from 88% (86‒89) during the first month after full vaccination to 47% (43‒51) after ≥5 months. Among sequenced infections, VE against Delta was lower compared to VE against other variants (75% [71‒78] vs 91% [88‒92]). VE against Delta infections was high during the first month after full vaccination (93% [85‒97]) but declined to 53% [39‒65] at ≥4 months. VE against hospitalization for Delta for all ages was high overall (93%).”

This preprint was posted on August 23, 2021. It was funded by Pfizer and seven of the 15 authors have their affiliation listed as Pfizer.

The study (#7) by Pouwels et al. (6) WAS included in the pre-vote presentation by Dr. Gargano (footnote 16), despite similar publication dates as the above-mentioned non-included papers. This study examined VE in the Pfizer (BNT162b2), Moderna, and Astra-Zeneca (ChAdOx1) vaccines and concluded: “SARS-CoV-2 vaccination still reduces new infections, but effectiveness and attenuation of peak viral burden are reduced with Delta.”

“Importantly, attenuations in the Delta-dominant period now reached statistical significance for BNT162b2 as well as ChAdOx1 (e.g. Ct<30 VE 14 days post second dose 84% (82-86%) Delta versus 94% (91-96%) Alpha (heterogeneity p<0.0001), and 70% (65-73%) versus 86% (71-93%) respectively for ChAdOx1 (heterogeneity p=0.04)).”

The study was posted as a preprint on medrxiv on August 24. However, as cited by CDC, the study first appeared on the Nuffield Department of Medicine (University of Oxford) website. The file name suggests the date of file to be August 16, 2021. Inspection of the html code for the referenced link

https://www.ndm.ox.ac.uk/files…nalcombinedve20210816.pdf reveals the date last modified as Wednesday August 18, 2021.

We see therefore a total of six papers, cited in a presentation AFTER ACIP’s vote, describing waning or reduced immunity against delta appear to have been completely or partially (pertinent part) omitted from the evidence presented (footnote 13) by CDC to ACIP on the benefits and harms of the Pfizer vaccine, PRIOR to its vote on the recommendation. Of these six, four (20-22,25) clearly met the cut-off date for inclusion of August 20. Of these four, one of these (22), WAS referenced in the pre-vote presentation by Dr. Gargano (footnote 16), however, the finding of 42% effectiveness against infection does not appear to have been tabulated.

One study (23) was published as an early release in MMWR on Aug 24, by CDC staff. Another study (26) was posted on August 23 and was funded by Pfizer and included Pfizer scientists. Given the inclusion in the pre-vote CDC presentation (footnote 13) of unpublished data, (footnote 14) despite not meeting the Aug 20 cut-off date, as well as the inclusion of unpublished CDC data in earlier evidence presented (footnote 4) to ACIP, it is difficult to justify why these two studies were omitted from the pre-vote evidence. The apparent omission of a study funded by Pfizer funded (which included as authors Pfizer scientists) (26) from the evidence presented by the Pfizer representative (footnote 12) requires explanation.

Lastly, the August 20 cut-off date for including studies in the evidence (footnote 13) presented immediately before ACIP’s vote appears arbitrary, given their inclusion in the evidence presented after the vote (footnote 15).

How would the inclusion of data showing lower levels of vaccine effectiveness change the risk-benefit analysis?

Once vaccine effectiveness falls from the 90-95% range towards and below 50% any risk-benefit analysis would change greatly, placing these vaccines in close competition with repurposed drugs with far fewer safety concerns, and effectiveness under different scenarios of 30-60% [hydroxychloroquine; (27-29) ivermectin; (30,31) fluvoxamine; (32) Zinc/Vitamin D/other Vitamins (33,34) ]. Options are running out as we race towards authorizing a booster dose. FDA, NIH, and CDC, in appearing to endorse the recent surge in media attacks on repurposed drugs, particularly ivermectin, may have backed themselves into a corner. At the same time, Pfizer has announced that the first patient in their phase 2/3 study received a dose of their proprietary PF-07321332 – a drug intended to treat “non-hospitalized, symptomatic adult participants who have a confirmed diagnosis of SARS-CoV-2 infection and are not at increased risk of progressing to severe illness, which may lead to hospitalization or death.” (35)

If plan A is to rely on the vaccines, and the post hoc plan B to rely on booster doses, is plan C to wait another year for the arrival of PF-07321332?

Booster Doses

The post-vote discussion on booster doses from Dr. Oliver (footnote 14) focused mainly only on existing data on waning immunity and reduced effectiveness against delta. The discussants recognized the challenges in producing reliable data that could support the use of booster doses and a plan was outlined to be able to obtain data that could support an ACIP recommendation for booster doses following a planned approval by FDA mid- September. It is unclear what data currently exist or would even be available by that time.

Dr. Oliver certainly stated that it was important to determine both the safety and effectiveness of the booster doses.

Slide 29 from presentation of Dr. Oliver (footnote 14)

The use of the term “booster” was questioned and suggested to have less positive connotations than positioning the “third dose” as merely one in a series of a planned course of immunizations, similar to that used for other kinds of vaccines. This has clearly not been the case with the Covid-19 vaccines. Had this been planned, then provision could have been made within the pivotal trials to study the effects of boosters. This is all but precluded now with the substantive loss of blinding in those studies. (36)

Any assessment of safety for third doses must be considered alongside the significant short- and long-term safety questions that remain after two doses.

As for the effectiveness of the third dose, there are few data now emerging. One recent study(37) did suggest that waning or reduced immunity can be restored with a booster dose, but this is only partial, and is at best, according to the study, temporary.

Why was it necessary for ACIP to issue this recommendation?

Extensive discussion preceded the vote based on a presentation: “Evidence to Recommendations Framework: Pfizer-BioNTech COVID-19 vaccine”.[23] One primary concern of that discussion was the issue of vaccine hesitancy. In one survey unvaccinated people were asked:

“Would you be more likely to get vaccinated if one of the vaccines currently authorized for emergency use received full approval from the FDA” (emphasis added)

Of these, “31% of unvaccinated respondents said they would be more likely to get vaccinated after full FDA vaccine approval,” meaning – OF ANY OF THE VACCINES.

This provides the possible rationale for the FDA’s puzzling approval of a vaccine that does not exist. CDC took this to the next step, inferring that not only would FDA approval of ANY of the vaccines be necessary to overcome at least 31% of vaccine hesitancy but that a CDC/ACIP recommendation would also be required.

Slides 37 and 43 from presentation by Dr. Dooling (footnote 18)

Accordingly, it was felt that a recommendation from ACIP, such as the one approved, along with full FDA approval (i.e. BLA) for at least one of the vaccines, would be a significant step in reducing vaccine hesitancy. Presumably, this rationale prevailed at FDA when they puzzlingly issued to BioNTech (as opposed to Pfizer/BioNTech) the BLA for a vaccine (COMIRNATY) on August 23 that was not yet available in the USA.

ACIPs recommendation is even more puzzling. Its wording takes no account of the legal reality of there being two legally distinct vaccines as the FDA explains [footnote 8 in (38)]. For this legal distinction to have any meaning, there would need to exist the ability in VAERS to report and track separately the two legally distinct vaccines. We should expect to see under the list of manufacturers both BioNnTech and Pfizer/BioNTech. We do not (9/6/21). The wording of the recommendation is therefore misleading to the point of being meaningless because on the one hand it speaks about the “Pfizer-BioNTech Covid-19 vaccine”(still under EUA) and on the other hand it speaks of BLA approval (COMIRNATY COVID-19 Vaccine, mRNA).

Did scientific misconduct occur?

We pointed out at the outset of this paper, the CDC endorsement of ACIP’s recommendation, once published in MMWR will “represent the official CDC recommendations for immunizations in the United States.”[24] CDC’s endorsement is already having enormous ramifications as to public policy on vaccine mandates and testing. Accordingly, the evidence presented to ACIP by Pfizer and CDC scientists must meet the highest level of standards for scientific integrity and conduct. The inclusion of key studies evincing lowered effectiveness from the 90-95% range to as low as 42%, would surely have resulted in a different risk-benefit analysis. Is this not akin to the withholding of evidence by lawyers in a trial?

“Scientific misconduct” is defined by CDC [25]

“Under applicable federal regulations found at 42 CFR Part 93 [subpart 103 see [26] (39)], research misconduct is defined as fabrication, falsification or plagiarism in proposing, performing or reviewing research, or in reporting research results. Research misconduct does not include honest errors, differences of opinion, or authorship disputes.” (emphasis added)

I will leave it to the ethicists and lawyers to determine whether or not what happened on August 30 violated any laws, regulations, or codes of ethics. I can only hope that the discrepancies noted in this article are the result of the demands imposed by pandemic conditions that impair the diligence of otherwise well-intentioned people. If that is the explanation, then matters must still be corrected. Uncorrected, for me, none of this passes the smell test. Has Covid has caused everyone to lose their sense of smell.

Acknowledgements and Funding

I am grateful to the many new colleagues I have acquired during the Covid-19 pandemic who have dedicated their talents and time to solving this problem and who have provided inspiration as well as stimulating discussion.

I acknowledge and appreciate the generous support of Mr. Steve Kirsch for work related to Covid-19. My company has previously received consulting and research contract fees from many companies outside the area of Covid-19, including from Johnson & Johnson.

References

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2. Wiseman D. Follow up Comment submitted to August 30 2021 meeting of the Advisory Committee on Immunization Practices (Centers for Disease Control). Docket CDC-2021-0089-0039. 2021 Aug 30. at https://www.regulations.gov/comment/CDC-2021-0089-0039.)

3. Barda N, Dagan N, Ben-Shlomo Y, et al. Safety of the BNT162b2 mRNA Covid-19 Vaccine in a Nationwide Setting. N Engl J Med 2021. Epub 2021/08/26 http://doi.org/10.1056/NEJMoa2110475

4. Singer ME, Taub IB, Kaelber DC. Risk of Myocarditis from COVID-19 Infection in People Under Age 20: A Population-Based Analysis. medRxiv 2021:2021.07.23.21260998. Epub Jul 27 http://doi.org/10.1101/2021.07.23.21260998

5. Gupta S, Cantor J, Simon KI, et al. Vaccinations Against COVID-19 May Have Averted Up To 140,000 Deaths In The United States. Health affairs (Project Hope) 2021:101377hlthaff202100619. Epub 2021/08/19 http://doi.org/10.1377/hlthaff.2021.00619

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7. Chau NVVN, Nghiem My; Nguyet, Lam Anh; et al. Transmission of SARS-CoV-2 Delta Variant Among Vaccinated Healthcare Workers, Vietnam. . Alncet Preprints 2021. Epub Aug 10 http://doi.org/http://dx.doi.org/10.2139/ssrn.3897733

8. Kang M, Wei J, Yuan J, et al. Probable Evidence of Fecal Aerosol Transmission of SARS-CoV-2 in a High-Rise Building. Ann Intern Med 2020; 173:974-80. Epub 2020/09/02 http://doi.org/10.7326/M20-0928

9. VAERS. Immunization Safety Office, Division of Healthcare Quality Promotion National Center for Emerging and Zoonotic Infectious Diseases Centers for Disease Control and Prevention. Vaccine Adverse Event Reporting System (VAERS) Standard Operating Procedures for COVID-19. 2021 Jan 29. at https://www.cdc.gov/vaccinesafety/pdf/VAERS-v2-SOP.pdf.)

10. FDA. Package Insert for COMIRNATY. 2021 Aug 23. at https://www.fda.gov/media/151707/download.)

11. Klein NP, Lewis N, Goddard K, et al. Surveillance for Adverse Events After COVID-19 mRNA Vaccination. JAMA 2021. Epub Sep 3 http://doi.org/10.1001/jama.2021.15072

12. FDA. Food and Drug Administration. Long Term Follow-up After Administration of Human Gene Therapy Products. Guidance for Industry. FDA-2018-D-2173. 2020. (Accessed July 13, 2021, at https://www.fda.gov/regulatory…man-gene-therapy-products

https://www.fda.gov/media/113768/download.)

13. Moderna. QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended June 30, 2020. 2020 Aug 6. (Accessed July 22, 2021, at https://www.sec.gov/Archives/e…0000017/mrna-20200630.htm.)

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15. FDA. Summary Basis for Regulatory Action: COMIRNATY. 2021 Aug 23. (Accessed 2021, Aug 25, at https://www.fda.gov/media/151733/download.)

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18. Zauche LH, Wallace B, Smoots AN, et al. Receipt of mRNA Covid-19 Vaccines and Risk of Spontaneous Abortion. New England Journal of Medicine 2021. Epub Sep 8 http://doi.org/10.1056/NEJMc2113891

19. Thomas SJ, Moreira ED, Kitchin N, et al. Six Month Safety and Efficacy of the BNT162b2 mRNA COVID-19 Vaccine. medRxiv 2021:2021.07.28.21261159. Epub Jul 28 http://doi.org/10.1101/2021.07.28.21261159

20. Nanduri S, Pilishvili T, Derado G, et al. Effectiveness of Pfizer-BioNTech and Moderna Vaccines in Preventing SARS-CoV-2 Infection Among Nursing Home Residents Before and During Widespread Circulation of the SARS-CoV-2 B.1.617.2 (Delta) Variant – National Healthcare Safety Network, March 1-August 1, 2021. MMWR Morb Mortal Wkly Rep 2021; 70:1163-6. Epub 2021/08/27 http://doi.org/10.15585/mmwr.mm7034e3

21. Rosenberg ES, Holtgrave DR, Dorabawila V, et al. New COVID-19 Cases and Hospitalizations Among Adults, by Vaccination Status – New York, May 3-July 25, 2021. MMWR Morb Mortal Wkly Rep 2021; 70:1150-5. Epub 2021/08/27 http://doi.org/10.15585/mmwr.mm7034e1

22. Puranik A, Lenehan PJ, Silvert E, et al. Comparison of two highly-effective mRNA vaccines for COVID-19 during periods of Alpha and Delta variant prevalence. medRxiv 2021. Epub 2021/08/18 http://doi.org/10.1101/2021.08.06.21261707

23. Fowlkes A, Gaglani M, Groover K, et al. Effectiveness of COVID-19 Vaccines in Preventing SARS-CoV-2 Infection Among Frontline Workers Before and During B.1.617.2 (Delta) Variant Predominance – Eight U.S. Locations, December 2020-August 2021. MMWR Morb Mortal Wkly Rep 2021; 70:1167-9. Epub 2021/08/27 http://doi.org/10.15585/mmwr.mm7034e4

24. Tenforde MW, Self WH, Naioti EA, et al. Sustained Effectiveness of Pfizer-BioNTech and Moderna Vaccines Against COVID-19 Associated Hospitalizations Among Adults – United States, March-July 2021. MMWR Morb Mortal Wkly Rep 2021; 70:1156-62. Epub 2021/08/27 http://doi.org/10.15585/mmwr.mm7034e2

25. Sheikh A, McMenamin J, Taylor B, et al. SARS-CoV-2 Delta VOC in Scotland: demographics, risk of hospital admission, and vaccine effectiveness. Lancet 2021; 397:2461-2. Epub 2021/06/18 http://doi.org/10.1016/S0140-6736(21)01358-1

26. Tartof SY, Slezak, Jeff M. , Fischer, Heidi, Hong, Vennis, Ackerson, Bradley K., Ranasinghe, Omesh N., Frankland, Timothy B., Ogun, Oluwaseye A., Zamparo, Joann M., Gray, Sharon, Valluri, Srinivas R., Pan, Kaijie, Angulo, Frederick J., Jodar, Luis, McLaughlin, John M., . Six-Month Effectiveness of BNT162B2 mRNA COVID-19 Vaccine in a Large US Integrated Health System: A Retrospective Cohort Study. . SSRN 2021. Epub Aug 23 http://doi.org/dx.doi.org/10.2139/ssrn.3909743

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28. Wiseman D. Missing data and flawed analyses reverse or challenge findings of three key studies cited in Covid-19 Guidelines: Guideline revision warranted for PEP and PrEP use of Hydroxychloroquine (HCQ). Letter to NIH Covid-19 Treatment Guidelines Panel. 2020 31 Dec. at https://osf.io/7trh4/.)

29. Wiseman DM, Kory P, Saidi SA, Mazzucco D. Effective post-exposure prophylaxis of Covid-19 is associated with use of hydroxychloroquine: Prospective re-analysis of a public dataset incorporating novel data. medRxiv 2021:2020.11.29.20235218. Epub July 5 http://doi.org/10.1101/2020.11.29.20235218

30. Wiseman D, Kory, P. Possible clustering and/or drug switching confounding obscures up to 56% reduction of symptom persistence by ivermectin. Data Summary for comment posted to JAMA re: Lopez-Medina et al. OSF Preprints 2021. Epub April 7 http://doi.org/https://doi.org/10.31219/osf.io/bvznd

31. Bryant A, Lawrie TA, Dowswell T, et al. Ivermectin for Prevention and Treatment of COVID-19 Infection: A Systematic Review, Meta-analysis, and Trial Sequential Analysis to Inform Clinical Guidelines. American journal of therapeutics 2021. Epub June 17 http://doi.org/DOI: 10.1097/MJT.0000000000001442

32. Together, Reis G, Silva E, et al. Effect of early treatment with fluvoxamine on risk of emergency care and hospitalization among patients with covid-19: the Together randomized platform clinical trial. medRxiv 2021:2021.08.19.21262323. Epub http://doi.org/10.1101/2021.08.19.21262323

33. Hazan S, Dave S, Gunaratne AW, et al. Effectiveness of Ivermectin-Based Multidrug Therapy in Severe Hypoxic Ambulatory COVID-19 Patients. medRxiv 2021:2021.07.06.21259924. Epub July 7 http://doi.org/10.1101/2021.07.06.21259924

34. Procter MDBC, Aprn FNPCCRMSN, Pa-C MVP, et al. Early Ambulatory Multidrug Therapy Reduces Hospitalization and Death in High-Risk Patients with SARS-CoV-2 (COVID-19). International Journal of Innovative Research in Medical Science 2021; 6:219 – 21. Epub http://doi.org/10.23958/ijirms/vol06-i03/1100

35. Pfizer. First Participant Dosed in Phase 2/3 Study of Oral Antiviral Candidate in Non-Hospitalized Adults with COVID-19 Who Are at Low Risk of Severe Illness. 2021 Sept 1. (Accessed Sep 9, 2021, at https://cdn.pfizer.com/pfizerc…nt_Dosed_in_Phase_2_3.pdf.)

36. Doshi P. Covid-19 vaccines: In the rush for regulatory approval, do we need more data? BMJ 2021; 373:n1244. Epub 2021/05/20 http://doi.org/10.1136/bmj.n1244

37. Levine-Tiefenbrun M, Yelin I, Alapi H, et al. Viral loads of Delta-variant SARS-CoV2 breakthrough infections following vaccination and booster with the BNT162b2 vaccine. medRxiv 2021:2021.08.29.21262798. Epub Sep 1 http://doi.org/10.1101/2021.08.29.21262798

38. FDA. Letter to Pfizer – Vaccine Approval. 2021 Aug 23. (Accessed Aug 23, 2021, at https://www.fda.gov/media/150386/download.)

39. Public Health Service Policies on Research Misconduct (Accessed Sept 1, 2021, at https://ecfr.federalregister.g…er-I/subchapter-H/part-93.)

Appendix: Html code for Pouwels et al paper on NDM Web site August18, 2021 (key sections marked)

1. Wiseman D, Guetzkow, J,, Seligmann H. Comment submitted to August 30 2021 meeting of the Advisory Committee on Immunization Practices (Centers for Disease Control). Docket CDC-2021-0089-0023. 2021 Aug 29. at https://www.regulations.gov/comment/CDC-2021-0089-0023.)

2. Wiseman D. Follow up Comment submitted to August 30 2021 meeting of the Advisory Committee on Immunization Practices (Centers for Disease Control). Docket CDC-2021-0089-0039. 2021 Aug 30. at https://www.regulations.gov/comment/CDC-2021-0089-0039.)

3. Barda N, Dagan N, Ben-Shlomo Y, et al. Safety of the BNT162b2 mRNA Covid-19 Vaccine in a Nationwide Setting. N Engl J Med 2021. Epub 2021/08/26 http://doi.org/10.1056/NEJMoa2110475

4. Singer ME, Taub IB, Kaelber DC. Risk of Myocarditis from COVID-19 Infection in People Under Age 20: A Population-Based Analysis. medRxiv 2021:2021.07.23.21260998. Epub Jul 27 http://doi.org/10.1101/2021.07.23.21260998

5. Gupta S, Cantor J, Simon KI, et al. Vaccinations Against COVID-19 May Have Averted Up To 140,000 Deaths In The United States. Health affairs (Project Hope) 2021:101377hlthaff202100619. Epub 2021/08/19 http://doi.org/10.1377/hlthaff.2021.00619

6. Pouwels KB, Pritchard E, Matthews P, et al. Impact of Delta on viral burden and vaccine effectiveness against new SARS-CoV-2 infections in the UK. medRxiv 2021:2021.08.18.21262237. Epub Aug 24 http://doi.org/10.1101/2021.08.18.21262237

7. Chau NVVN, Nghiem My; Nguyet, et al. Transmission of SARS-CoV-2 Delta Variant Among Vaccinated Healthcare Workers, Vietnam. . Alncet Preprints 2021. Epub Aug 10 http://doi.org/http://dx.doi.org/10.2139/ssrn.3897733

8. Kang M, Wei J, Yuan J, et al. Probable Evidence of Fecal Aerosol Transmission of SARS-CoV-2 in a High-Rise Building. Ann Intern Med 2020; 173:974-80. Epub 2020/09/02 http://doi.org/10.7326/M20-0928

9. VAERS. Immunization Safety Office, Division of Healthcare Quality Promotion National Center for Emerging and Zoonotic Infectious Diseases Centers for Disease Control and Prevention. Vaccine Adverse Event Reporting System (VAERS) Standard Operating Procedures for COVID-19. 2021 Jan 29. at https://www.cdc.gov/vaccinesafety/pdf/VAERS-v2-SOP.pdf.)

10. FDA. Package Insert for COMIRNATY. 2021 Aug 23. at https://www.fda.gov/media/151707/download.)

11. Klein NP, Lewis N, Goddard K, et al. Surveillance for Adverse Events After COVID-19 mRNA Vaccination. JAMA 2021. Epub Sep 3 http://doi.org/10.1001/jama.2021.15072

12. FDA. Food and Drug Administration. Long Term Follow-up After Administration of Human Gene Therapy Products. Guidance for Industry. FDA-2018-D-2173. 2020. (Accessed July 13, 2021, at https://www.fda.gov/regulatory…man-gene-therapy-products

https://www.fda.gov/media/113768/download.)

13. Moderna. QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended June 30, 2020. 2020 Aug 6. (Accessed July 22, 2021, at https://www.sec.gov/Archives/e…0000017/mrna-20200630.htm.)

14. FDA. BLA Approval for BioNtech COMIRNATY Vaccine. 2021. (Accessed Aug 23, 2021, at https://www.fda.gov/media/151710/download.)

15. FDA. Summary Basis for Regulatory Action: COMIRNATY. 2021 Aug 23. (Accessed 2021, Aug 25, at https://www.fda.gov/media/151733/download.)

16. Cotton C. VAERS DATA ANALYSIS. 2021 Jul 23. (Accessed Aug 17, 2021, at https://www.francesoir.fr/site…sis_report-2021-08-08.pdf.)

17. Shimabukuro TT, Kim SY, Myers TR, et al. Preliminary Findings of mRNA Covid-19 Vaccine Safety in Pregnant Persons. N Engl J Med 2021; 384:2273-82. Epub 2021/04/22 http://doi.org/10.1056/NEJMoa2104983

18. Zauche LH, Wallace B, Smoots AN, et al. Receipt of mRNA Covid-19 Vaccines and Risk of Spontaneous Abortion. New England Journal of Medicine 2021. Epub Sep 8 http://doi.org/10.1056/NEJMc2113891

19. Thomas SJ, Moreira ED, Kitchin N, et al. Six Month Safety and Efficacy of the BNT162b2 mRNA COVID-19 Vaccine. medRxiv 2021:2021.07.28.21261159. Epub Jul 28 http://doi.org/10.1101/2021.07.28.21261159

20. Nanduri S, Pilishvili T, Derado G, et al. Effectiveness of Pfizer-BioNTech and Moderna Vaccines in Preventing SARS-CoV-2 Infection Among Nursing Home Residents Before and During Widespread Circulation of the SARS-CoV-2 B.1.617.2 (Delta) Variant – National Healthcare Safety Network, March 1-August 1, 2021. MMWR Morb Mortal Wkly Rep 2021; 70:1163-6. Epub 2021/08/27 http://doi.org/10.15585/mmwr.mm7034e3

21. Rosenberg ES, Holtgrave DR, Dorabawila V, et al. New COVID-19 Cases and Hospitalizations Among Adults, by Vaccination Status – New York, May 3-July 25, 2021. MMWR Morb Mortal Wkly Rep 2021; 70:1150-5. Epub 2021/08/27 http://doi.org/10.15585/mmwr.mm7034e1

22. Puranik A, Lenehan PJ, Silvert E, et al. Comparison of two highly-effective mRNA vaccines for COVID-19 during periods of Alpha and Delta variant prevalence. medRxiv 2021. Epub 2021/08/18 http://doi.org/10.1101/2021.08.06.21261707

23. Fowlkes A, Gaglani M, Groover K, et al. Effectiveness of COVID-19 Vaccines in Preventing SARS-CoV-2 Infection Among Frontline Workers Before and During B.1.617.2 (Delta) Variant Predominance – Eight U.S. Locations, December 2020-August 2021. MMWR Morb Mortal Wkly Rep 2021; 70:1167-9. Epub 2021/08/27 http://doi.org/10.15585/mmwr.mm7034e4

24. Tenforde MW, Self WH, Naioti EA, et al. Sustained Effectiveness of Pfizer-BioNTech and Moderna Vaccines Against COVID-19 Associated Hospitalizations Among Adults – United States, March-July 2021. MMWR Morb Mortal Wkly Rep 2021; 70:1156-62. Epub 2021/08/27 http://doi.org/10.15585/mmwr.mm7034e2

25. Sheikh A, McMenamin J, Taylor B, et al. SARS-CoV-2 Delta VOC in Scotland: demographics, risk of hospital admission, and vaccine effectiveness. Lancet 2021; 397:2461-2. Epub 2021/06/18 http://doi.org/10.1016/S0140-6736(21)01358-1

26. Tartof SY, Slezak, Jeff M. , Fischer, Heidi, Hong, Vennis, Ackerson, Bradley K., Ranasinghe, Omesh N., Frankland, Timothy B., Ogun, Oluwaseye A., Zamparo, Joann M., Gray, Sharon, Valluri, Srinivas R., Pan, Kaijie, Angulo, Frederick J., Jodar, Luis, McLaughlin, John M., . Six-Month Effectiveness of BNT162B2 mRNA COVID-19 Vaccine in a Large US Integrated Health System: A Retrospective Cohort Study. . SSRN 2021. Epub Aug 23 http://doi.org/dx.doi.org/10.2139/ssrn.3909743

27. Dinesh B, J CS, Kaur CP, et al. Hydroxychloroquine for SARS CoV2 Prophylaxis in Healthcare Workers – A Multicentric Cohort Study Assessing Effectiveness and Safety. J Assoc Physicians India 2021; 69:11-2. Epub 2021/09/03

28. Wiseman D. Missing data and flawed analyses reverse or challenge findings of three key studies cited in Covid-19 Guidelines: Guideline revision warranted for PEP and PrEP use of Hydroxychloroquine (HCQ). Letter to NIH Covid-19 Treatment Guidelines Panel. 2020 31 Dec. at https://osf.io/7trh4/.)

29. Wiseman DM, Kory P, Saidi SA, Mazzucco D. Effective post-exposure prophylaxis of Covid-19 is associated with use of hydroxychloroquine: Prospective re-analysis of a public dataset incorporating novel data. medRxiv 2021:2020.11.29.20235218. Epub July 5 http://doi.org/10.1101/2020.11.29.20235218

30. Wiseman D, Kory, P. Possible clustering and/or drug switching confounding obscures up to 56% reduction of symptom persistence by ivermectin. Data Summary for comment posted to JAMA re: Lopez-Medina et al. OSF Preprints 2021. Epub April 7 http://doi.org/https://doi.org/10.31219/osf.io/bvznd

31. Bryant A, Lawrie TA, Dowswell T, et al. Ivermectin for Prevention and Treatment of COVID-19 Infection: A Systematic Review, Meta-analysis, and Trial Sequential Analysis to Inform Clinical Guidelines. American journal of therapeutics 2021. Epub June 17 http://doi.org/DOI: 10.1097/MJT.0000000000001442

32. Together, Reis G, Silva E, et al. Effect of early treatment with fluvoxamine on risk of emergency care and hospitalization among patients with covid-19: the Together randomized platform clinical trial. medRxiv 2021:2021.08.19.21262323. Epub http://doi.org/10.1101/2021.08.19.21262323

33. Hazan S, Dave S, Gunaratne AW, et al. Effectiveness of Ivermectin-Based Multidrug Therapy in Severe Hypoxic Ambulatory COVID-19 Patients. medRxiv 2021:2021.07.06.21259924. Epub July 7 http://doi.org/10.1101/2021.07.06.21259924

34. Procter MDBC, Aprn FNPCCRMSN, Pa-C MVP, et al. Early Ambulatory Multidrug Therapy Reduces Hospitalization and Death in High-Risk Patients with SARS-CoV-2 (COVID-19). International Journal of Innovative Research in Medical Science 2021; 6:219 – 21. Epub http://doi.org/10.23958/ijirms/vol06-i03/1100

35. Pfizer. First Participant Dosed in Phase 2/3 Study of Oral Antiviral Candidate in Non-Hospitalized Adults with COVID-19 Who Are at Low Risk of Severe Illness. 2021 Sept 1. (Accessed Sep 9, 2021, at https://cdn.pfizer.com/pfizerc…nt_Dosed_in_Phase_2_3.pdf.)

36. Doshi P. Covid-19 vaccines: In the rush for regulatory approval, do we need more data? BMJ 2021; 373:n1244. Epub 2021/05/20 http://doi.org/10.1136/bmj.n1244

37. Levine-Tiefenbrun M, Yelin I, Alapi H, et al. Viral loads of Delta-variant SARS-CoV2 breakthrough infections following vaccination and booster with the BNT162b2 vaccine. medRxiv 2021:2021.08.29.21262798. Epub Sep 1 http://doi.org/10.1101/2021.08.29.21262798

38. FDA. Letter to Pfizer – Vaccine Approval. 2021 Aug 23. (Accessed Aug 23, 2021, at https://www.fda.gov/media/150386/download.)

39. Public Health Service Policies on Research Misconduct (Accessed Sept 1, 2021, at https://ecfr.federalregister.g…er-I/subchapter-H/part-93.)

[1] http://www.cdc.gov/media/relea…21/s0830-pfizer-vote.html

[2] http://www.cdc.gov/vaccines/ac…cine-recommendations.html

[3] http://www.cdc.gov/about/organization/mission.htm

[4] http://www.cdc.gov/vaccines/ac…6-COVID-Rosenblum-508.pdf

[5] As far as we can tell, the only statement regarding these deaths appears on CDC’s web site (9/2/21) “Reports of death after COVID-19 vaccination are rare. More than 369 million doses of COVID-19 vaccines were administered in the United States from December 14, 2020, through August 30, 2021. During this time, VAERS received 7,218 reports of death (0.0020%) among people who received a COVID-19 vaccine. FDA requires healthcare providers to report any death after COVID-19 vaccination to VAERS, even if it’s unclear whether the vaccine was the cause. Reports of adverse events to VAERS following vaccination, including deaths, do not necessarily mean that a vaccine caused a health problem. A review of available clinical information, including death certificates, autopsy, and medical records, has not established a causal link to COVID-19 vaccines.” (their emphasis)

[6] http://www.cdc.gov/vaccines/ac…8-30/05-COVID-Lee-508.pdf

[7] With about 2/3 of the US population vaccinated, we would expect about 5000 per deaths to occur every day from non-Covid-19 causes. Using a conservative 30-day follow up, we would expect to see 150,000 deaths reported in VAERS. As of 8/29/21, 6128 deaths (USA, territories and unknown) have been reported in connection with Covid-19 vaccines (4805 deaths 50 States and Washington DC). The system does not appear to be functioning as designed.

[8] This is another safety monitoring system used by CDC in collaboration with Kaiser Permanente.

[9] http://www.cdc.gov/vaccines/ac…30/04-COVID-Klein-508.pdf

[10] The get-out-of-jail-free card for these guidance documents is that there are not legally binding.

[11] http://www.nichd.nih.gov/newsr…-vaccination-menstruation

[12] 9/3/21 – searched under “USA, Territories and Unknown” using the terms AMENORRHOEA, DYSMENORRHOEA, HEAVY MENSTRUAL BLEEDING, HYPOMENORRHOEA, MENORRHAGIA, MENSTRUATION DELAYED, MENSTRUATION IRREGULAR.

[13] See http://www.adhesions.org and http://www.iscapps.org

[14] https://www.fda.gov/drugs/guid…uirements-and-commitments

[15] http://www.accessdata.fda.gov/…17/761061Orig1s000ltr.pdf

[16] http://www.accessdata.fda.gov/…21/761123Orig1s000ltr.pdf

[17] http://www.cdc.gov/vaccines/ac…6-COVID-Rosenblum-508.pdf

[18] According to one writer, those choosing to remain unvaccinated, rather than being demonized, should be thanked for serving as a valuable control population enabling the effects of vaccines to be more fully evaluated.

[19] http://www.cdc.gov/vaccines/ac…30/02-COVID-perez-508.pdf

[20] http://www.cdc.gov/vaccines/ac…/07-COVID-Gargano-508.pdf

[21] Slide 14 in footnote 13: Polack et al., “additional unpublished data obtained from authors”

[22] http://www.cdc.gov/vaccines/ac…0/09-COVID-Oliver-508.pdf

[23] http://www.cdc.gov/vaccines/ac…/08-COVID-Dooling-508.pdf

[24] http://www.cdc.gov/vaccines/ac…cine-recommendations.html

[25] http://www.cdc.gov/os/integrity/researchmisconduct/index.htm

[26] https://ori.hhs.gov/FR_Doc_05-9643

Note that views expressed in this opinion article are the writer’s personal views and not necessarily those of TrialSite

Cleveland Clinic Retrospective Study Indicates Obese Patients Face Higher Probability of Long COVID

Cleveland Clinic Retrospective Study Indicates Obese Patients Face Higher Probability of Long COVID

Cleveland Clinic researchers recently completed a study indicating long-term COVID-19 complications may be more pronounced in individuals struggling with

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Cleveland Clinic researchers recently completed a study indicating long-term COVID-19 complications may be more pronounced in individuals struggling with obesity. Led by Dr. Ali Aminian with Cleveland Clinic’s Bariatric and Metabolic Institute in the Department of General Surgery, the published study indicates that those diagnosed with moderate to severe obesity face a 30% higher risk associated with long-COVID.

The Study

The Cleveland Clinic team performed a retrospective analysis of a prospective, observational, IRB-approved clinical registry of all patients tested positive by RT-PCR for SARS-CoV-2 infection within the Cleveland Clinic Health System (CCHS) from March 11, 2020, to July 30, 2020, with a follow-up review by January 27, 2021.

Several patient categories were excluded, from those with no Body Mass Index (BMI) data to individuals with a history of organ transplant, those currently pregnant, and more.

The Findings

The risk of hospitalization was 28% and 30% higher in patients with moderate and severe obesity, respectively, as compared to those patients with what is considered a normal BMI. Patients that were classified as moderate and severe required a 25% and 39% greater need for diagnostic tests.

Moreover, the investigators identified comparable patterns when ordering diagnostic tests evaluating cardiac, pulmonary, vascular, renal, and gastrointestinal systems, and mental health.

Among other things, a key indirect effect is associated with the study: that risk signs and symptoms associated with select body organs increase in patients with moderate and severe obesity compared to those with a normal measurement.

The study team argues that these findings indicate patients with obesity face higher risks for post-acute sequelae of COVID-19 (PASC) or “Long Covid.”

Study Limitations

Of course, this study has some limitations. TrialSite provides a list below:

Observational study with retrospective design from one single healthcare system

Use of electronic records and inherent limitations associated with data capture

Reason or hospitalization or other interaction with the hospital not known

True prevalence of PAS remains unknown

Other comorbidities could impact results

The study team found that the data suggests that moderate and severe obesity, a measurement of BMI ≥ 35 kg/m2, is associated with a greater risk of long-COVID. The authors declare that if further studies substantiate these results, a more proactive care plan for patients with obesity following COVID-19 infection is needed.

Lead Research/Investigator

Ali Aminian, MD

James Bena, MS

Kevin M. Pantalone, DO

Bartolome Burguera, MD

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Platelets amplify endotheliopathy in COVID-19

AAAS

Abstract

Given the evidence for a hyperactive platelet phenotype in COVID-19, we investigated effector cell properties of COVID-19 platelets on endothelial cells (ECs). Integration of EC and platelet RNA sequencing revealed that platelet-released factors in COVID-19 promote an inflammatory hypercoagulable endotheliopathy. We identified S100A8 and S100A9 as transcripts enriched in COVID-19 platelets and were induced by megakaryocyte infection with SARS-CoV-2. Consistent with increased gene expression, the heterodimer protein product of S100A8/A9, myeloid-related protein (MRP) 8/14, was released to a greater extent by platelets from COVID-19 patients relative to controls. We demonstrate that platelet-derived MRP8/14 activates ECs, promotes an inflammatory hypercoagulable phenotype, and is a significant contributor to poor clinical outcomes in COVID-19 patients. Last, we present evidence that targeting platelet P2Y12 represents a promising candidate to reduce proinflammatory platelet-endothelial interactions. Together, these findings demonstrate a previously unappreciated role for platelets and their activation-induced endotheliopathy in COVID-19.

DISCUSSION

Severe COVID-19 is associated with a hypercoagulable state and robust inflammatory response that predisposes patients to macro- and microthrombotic events (34–38). The coordinated activation of the inflammatory and thrombotic response has been termed thromboinflammation. Levels of prothrombotic acute phase mediators, including fibrinogen, vWF, and D-dimer, are increased in COVID-19 patients, implicating the endothelium, platelets, and the coagulation system as likely mediators of thromboinflammation in COVID-19. The resulting endotheliopathy is thought to link inflammation, immune dysregulation, and thrombosis, and be a driver of poor clinical outcomes in COVID-19 patients (39, 40). Despite suggestions that SARS-CoV-2 triggers endotheliopathy (12, 13), recent experimental evidence supports indirect activating mechanisms driving EC injury in COVID-19 (14).

Platelets are first responders to vascular injury and act to bridge the immune system and thrombosis via activation and release of hemostatic and inflammatory mediators. Activated platelets secrete a host of proinflammatory mediators in the local microenvironment, altering the endothelium’s inflammatory and adhesive properties (18, 19). Activated platelets isolated from patients with inflammatory disease, such as systemic lupus erythematosus (SLE), HIV, and psoriasis, induce a proinflammatory EC phenotype (16, 20, 21). We and others previously reported that COVID-19 is associated with a hyperactive platelet phenotype (23, 24), characterized by increased platelet activation markers and a proinflammatory, prothrombotic transcriptome. Given the interconnection between activated platelets and the microvasculature, we explored whether platelet-released factors contribute to COVID-19 endotheliopathy.

Our study details how COVID-19 hyperactive platelets release factors that induce a proinflammatory and hypercoagulable endothelium (Fig. 7). The change in EC transcription directly correlated with alterations in the platelet transcriptome, connecting differences seen in these complementary cell types. Sequencing of the platelets used to incubate with ECs found a set of 523 platelet genes that are consistently associated with the proinflammatory EC transcriptomic pathway changes. This block of genes is potentially a unique COVID-19 platelet signature that merits future exploration and study.

Unbiased screening of candidate platelet genes differentially expressed in COVID-19 led to the identification of S100A8 and S100A9, and their protein product MRP8/14, as a likely candidate of platelet-mediated endotheliopathy. Platelet S100A8/A9 mRNA and platelet-derived MRP8/14 were increased in patients with COVID, and their expression and translation positively correlate with changes seen in EC coagulation and inflammatory pathways and the production of IL6 and IL8, proinflammatory cytokines that regulate EC adhesion molecule expression (41). While circulating plasma MRP8/14 was once considered only to be leukocyte-derived (42), platelets and megakaryocytes serve as an additional source of MRP8/14 (31, 32, 43, 44). While circulating plasma levels of MRP8/14 alone correlated with EC coagulation and inflammatory pathways, platelet S100A8/A9 mRNA and releasate MRP8/14 levels were more tightly associated with EC dysfunction directly, suggesting the importance of platelet-derived MRP8/14 on EC dysfunction. Our present study does not rule out other cellular and noncellular contributors of COVID-19 endotheliopathy, which may act synergistically with MRP8/14. For example, serum antiphospholipid (aPL) antibodies in COVID-19 sera were recently reported to induce adhesion molecule expression on ECs (45). Previous studies have found that aPL antibodies promote platelet activation and their release of MRP8/14 into the microenvironment, providing evidence of additional mechanisms by which interaction of platelets with the local inflammatory environment in COVID-19 contributes to EC dysfunction (32, 46).

We find that the direct interaction of SARS-CoV-2 with primary megakaryocytes induces S100A8/A9 expression, a finding that has clinical implications given our observation that megakaryocytes from COVID-19 patients contain SARS-CoV-2 virions (26), and single-cell sequencing data reporting up-regulation of S100A9 in circulating megakaryocytes in COVID-19 (27). Intriguingly, up-regulation of S100A8/A9 does not occur following exposure of megakaryocytes to a coronavirus responsible for the common cold (CoV-OC43), highlighting that, independent of indirect mechanisms (e.g., systemic inflammation), SARS-CoV-2 can mediate proinflammatory changes to megakaryocytes and platelets (47, 48). Our data indicate that increased platelet S100A8/A9 mRNA translates to increased platelet MRP8/14 release, thus indicating that direct interactions of megakaryocytes with SARS-CoV-2 enhance proinflammatory platelet-EC interactions. Consistently, MRP8/14 is increased in activated platelets and platelets isolated from patients with peripheral artery disease and ST-elevation myocardial infarction. In vitro, MRP8/14 induces platelet surface P-selectin (31), a major ligand in the platelet-EC interaction. In addition, MRP-14−/− knockout mice had reduced expression of P-selectin in response to collagen and arachidonic acid, which was independent of platelet aggregation (44).

The prothrombotic and proinflammatory nature of platelet MRP8/14 is supported by studies finding platelet transcript expression of S100A8/A9, positively correlates with plasma MRP8/14 concentrations, and is predictive of future atherothrombotic events (31, 43). MRP8/14 levels are increased in patients with cardiovascular diseases, metabolic disease, and several inflammatory conditions, including rheumatoid arthritis, SLE, and psoriasis (31, 43, 49–51). Prior studies have found increased MRP8/14 in patients infected with SARS-CoV-2 (52, 53). In the current study, we find platelet S100A8 and S100A9 mRNA to be increased in COVID-19 patients and a corresponding increase in platelet-released MRP8/14, all of which correlate with circulating MRP8/14. Among 291 patients hospitalized with COVID-19, circulating MRP8/14 increased during hospitalization. When measured at baseline, MRP8/14 correlates with incident thrombotic events, severe disease, and length of stay. In contrast to a small increase in MRP8/14 among patients with nonsevere illness, levels increased up to eightfold in COVID-19 patients who subsequently died.

Recently, the therapeutic potential of suppressing MRP8/14 signaling has been suggested as an approach to reduce COVID-19–associated thromboinflammation (54). To understand the clinical potential of our findings, we investigated the (i) effect of antiplatelet therapy on S100A8/A9 platelet mRNA and (ii) in vitro effect of antiplatelet treatment on platelet-induced EC activation. In contrast to aspirin, targeting of P2Y12 with ticagrelor reduced S100A8 and S100A9 platelet mRNA. In vitro experiments found that P2Y12 inhibition significantly attenuated the COVID-19 platelet–mediated EC activation. The ability of aspirin to attenuate the platelet-EC interaction was less pronounced. The benefit of reducing platelet MRP8/14 release via targeting of P2Y12 is supported by murine studies, which found that the antithrombotic effect of the S100A9 vaccination is equivalent to that with clopidogrel (55). Furthermore, given evidence that P2Y12 inhibitors reduce platelet release of proinflammatory α-granule contents (56) and the formation of platelet-leukocyte aggregates (57), the beneficial effect of this approach is hypothesized to be multifaceted. These data collectively suggest that P2Y12 inhibition will mitigate platelet activation, reduce platelet-released MRP8/14, and ultimately suppress platelet activity and EC activation and improve clinical outcomes linked to COVID-19 thromboinflammation. While observational data suggested a potential benefit of aspirin on outcomes in hospitalized COVID-19 patients (58, 59), a large randomized trial of nearly 15,000 participants found that aspirin did not improve its primary end point of 28-day mortality (60). The clinical effect of a P2Y12 inhibitor strategy is being investigated in ACTIV4a (NCT04505774).

Our study describes how platelets isolated from hospitalized COVID-19 patients release significant quantities of MRP8/14 that can act in a paracrine fashion on nearby ECs promoting endotheliopathy. Several limitations exist with our current study: (i) the relatively small sample size used for sequencing; (ii) the cellular source of plasma MRP8/14 cannot definitively be attributed to platelets and may originate from other cells, including neutrophils; (iii) it is unknown whether the observed MRP8/14 induced endotheliopathy occurs in other viral settings; (iv) a clinical diagnosis of thrombosis during hospitalization may be underestimated because imaging studies were limited due to concerns of transmitting infection or competing risk of death; and (v) the effect of antiplatelet therapies on the COVID-19 platelet–induced EC activation was not explored. Future studies will aim to address these limitations to further our understanding of the interaction of platelets with SARS-CoV-2 and other viral illnesses and the endothelium. An ongoing multinational trial is underway exploring the effect of P2Y12 inhibition on clinical outcomes of hospitalized COVID-19 patients (NCT04505774).

In conclusion, we define a novel role for platelet-induced endotheliopathy in COVID-19. The activated platelet phenotype observed in COVID-19 consistently induces a proinflammatory and dysfunctional endothelium. Platelet-derived MRP8/14 is increased in COVID-19 and induces endothelial injury. Circulating MRP8/14 has the potential to serve as a useful biomarker of thrombosis and severity of disease in patients infected with SARS-CoV-2. Platelet-directed therapy, specifically P2Y12 inhibitors, may represent a particularly attractive therapy because of its effect on platelet S100A8/A9 and platelet-induced endotheliopathy (Fig. 7).

Gout Medicine Could Also Battle COVID-19 – FDA Approved and Has Potent Antiviral Properties

Gout Medicine Could Also Battle COVID-19 – FDA Approved and Has Potent Antiviral Properties

As COVID-19 cases continue to skyrocket across the U.S. and the world, few options are available for treating patients infected with the SARS-CoV-2. But new…

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As COVID-19 cases continue to skyrocket across the U.S. and the world, few options are available for treating patients infected with the SARS-CoV-2.

But new research from the University of Georgia offers hope for a viable therapeutic to combat the disease that has claimed more than 4 million lives worldwide.

Published in Nature’s Scientific Reports, the study found that probenecid has broad antiviral properties, making it a prime candidate to combat not only SARS-CoV-2 infection but also other common and deadly respiratory viruses like RSV and flu.

Probenecid is an FDA-approved medication that’s primarily used to treat gout, and it’s already widely available in the U.S. The drug has been on the market for over 40 years and has minimal side effects

There’s really nothing out there to safely fight these viruses,” said Ralph Tripp, lead author of the study and GRA Eminent Scholar of Vaccine and Therapeutic Studies in UGA’s College of Veterinary Medicine. “This antiviral works for all RNA respiratory viruses we tested, including SARS-CoV-2. RSV, coronavirus and flu all circulate in the same season. Bottom line is you can potentially reduce infection and disease using this one oral drug.”

Blocking viral reproduction

Viruses work by coopting a person’s own cells to replicate and produce more of the virus. Probenecid blocks that replication process, keeping the virus from infecting the individual’s cells.

In clinical development at the pharmaceutical company TrippBio, Tripp showed the drug works as a prophylactic prior to virus exposure and as a post-exposure treatment in animal models against SARS-CoV-2 and flu. The drug also has proven effective in fighting the RSV in vitro, and in vivo studies are in progress.

Although the drug would primarily be used after a person is positive for the virus, the prophylactic findings mean people with known exposures could also potentially take the drug to prevent getting sick.

COVID-19 treatment options limited

The current go-to treatments for seriously ill COVID-19 patients, remdesivir and monoclonal antibodies, can only be given through an IV. And by the time a COVID patient needs them, it’s often too late.

“These treatments have seen some effectiveness against SARS-CoV-2, but they’re very expensive and very hard to come by,” Tripp said. “In reality, there are only a handful of options that can actually be used because of the cost, restricted IV usage, and lack of access. That’s not very useful to the world.”

Probenecid, on the other hand, is widely available. Primary care physicians could prescribe a pill to patients, and they could pick it up at their local drugstore.

Repurposing drugs that are already approved to work against one problem is common. For example, remdesivir was originally intended to fight Ebola virus, but when it showed some promise in fighting the coronavirus, it was enlisted to battle COVID-19.

In addition to preventing illness before it starts, probenecid may also potentially increase the efficacy of other treatments. Probenecid is already used to up the potency of some antibiotics, so it’s possible the medication could work in conjunction with other COVID-19 treatments as well.

Now the researchers are investigating what dosage of probenecid could have the biggest impact fighting viruses in people. TrippBio is set to begin clinical trials of the medication within the year.

“SARS-CoV-2, RSV and flu have a huge impact on health systems throughout the world,” Tripp said. “Probenecid has a potent antiviral effect against these viruses, and it works safely.”

Probenecid is already FDA approved and has potent antiviral properties against SARS-CoV-2.

Reference: 10 September 2021, Scientific Reports.

DOI: 10.1038/s41598-021-97658-w