Covid-19 News

Novavax

Novavax

Image from novavax.com/our-unique-technology Stephen Ditmore, contributing writer When promising clinical trial results were reported for Novavax’

trialsitenews.com

Stephen Ditmore, contributing writer

When promising clinical trial results were reported for Novavax’ COVID-19 vaccine, top doctors took notice. Pfizer, Moderna, and J&J completed their clinical trials, beating Novavax to the EUA punch bowl; but as doubts grew that AstraZeneca’s vaccine would ever be authorized here, people supposed Novavax would be next in queue, and there was real enthusiasm that by the time we were ready to contemplate boosters, Novavax could be in American syringes, ready to take the plunge.

Instead, Novavax is going into production at the Serum Institute of India in preparation for distribution in that nation, Indonesia, and The Philippines. While a protein subunit vaccine is a gift to the world with virtues including storage at common refrigerator temperature, Novavax, inc. is strategically headquartered near our nation’s capital, and got into the COVID-19 vaccine effort with funding from the Coalition for Epidemic Preparedness Innovations (CEPI), and ultimately from Operation Warp Speed. What happened? Has there been a falling out between Novavax and the Biden Administration?

No doubt there is need around the world, but there are looming questions here in the U.S. We still have a massive COVID-19 epidemic on our hands, yet we’re a free country, made up of individuals who do not follow government recommendations slavishly. Why not put information, and choices, in front of individual Americans and let us decide for ourselves? Something about media reports and messaging from health authorities in the U.S. containing the two words “the vaccine”, clearly referring jointly to the Pfizer & Moderna mRNA shots, coupled with mandates, just rubs the wrong way.

While perhaps that ship – selection of the vaccines that dominate distributed to adults here in the U.S. — has sailed, another question has yet to be decided. For parents who would like to see their children vaccinated, there is no vaccine authorized for returning schoolchildren under 12. Understanding proper dosing of any COVID-19 vaccine for children will be a challenge. A protein subunit vaccine such as Novavax, which has already shown itself less reactogenic than the mRNA type, has real merit as a pediatric candidate. Dr. Marc Rendell of the Rose Salter Medical Research Foundation points out:

“The mRNA vaccines must induce the same level of systemic “infection”, with same expected adverse effects, every time they are re-administered in order to trigger an immune response. Novavax does not generate new spike protein, but rather delivers the same amount of spike protein at each administration, possibly with immediate immune reaction.”

All three of the U.S., authorized COVID-19 vaccines, and all seven of those thus far Emergency Use Listed by the World Health Organization, introduce genetic material into our cells (as do viruses). Novavax does not. Novavax can be thought of as similar to viral vectored vaccines, with a step added. Rather than inserting genetic material into human cells, the genetic material is introduced into moth cells, so spike protein is generated and harvested OUTSIDE the human body.

Image courtesy of Dr. Mobeen Syed, drbeen.com

Modern quality assurance is driven by the goal of meeting or exceeding customer expectation. What’s often debated is, who is the customer? Is it governments? In a free (and arguably consumer-driven) society, we expect to make choices, including the ones we make as parents. As Dr. Philip Ozuah, CEO of the Montefiore Medical Center recently said in an interview:

“I’ve been in medicine for over four decades, many of those decades as a pediatrician. Guess where most vaccines are given; in pediatrics. Over the last 30, 40 years, as dozens of new vaccines have been introduced to safeguard young ones against deadly disease, there has been hesitancy among parents. In the context of a trusting therapeutic relationship, we’ve worked through this. There is no vaccine in medicine that was 100% accepted on Day 1.”

If Pfizer or Moderna vaccine is authorized for children before what might be a better answer, Novavax, even has a chance, and especially if the former is mandated, is that a customer driven, or a corporate interest driven outcome? Is it government acting in loco parentis? It really is urgent, in the view of this contributor, that innovation in ethical clinical trial design, with government support, be applied to answering whether Novavax should be authorized for pediatric use, so that at least some answers are available when the time comes to make a decision about authorizing any COVID-19 vaccine for use in children.

Reportedly, both supply chain and quality assurance problems have hindered Novavax. At the start of July 2021, the following sentence appeared in Novavax’ second quarter financial filing:

“The U.S. government has recently instructed the Company to prioritize alignment with the U.S. Food and Drug Administration on the Company’s analytic methods before conducting additional U.S. manufacturing and further indicated that the U.S. government will not fund additional U.S. manufacturing until such agreement has been made.”

spooking some investors and prompting an article in Science Magazine suggesting an issue with assuring consistent potency. As we’ll discuss with respect to creating a pediatric COVID-19 vaccine, the ability to introduce consistent, controlled amounts of antigen into the body is a key advantage of protein subunit vaccines. To calm concerns prompted by this and the announcement that Novavax would delay their U.S. EUA filing until the fourth quarter, Novavax CEO Stanley Erck spoke with Yahoo News. When asked about the quality assurance issue, he pointed to issues at the facility of their Texas A&M production partner. That contract, it turns out, is between the U.S. Government in the party of HHS, Texas A&M, and Fujifilm Biosynth, with Novavax Inc. apparently a bystander. Novavax has recently hired additional industry professionals to its quality assurance team, but the process of technology transfer to multiple global partners while simultaneously training new hires remains challenging. Novavax is now banking on the largest vaccine supplier in the world (by volume, not revenue), the Serum Institute of India, to work through the issues with them.

There have been various things reported about the ongoing dialogue between Novavax and the U.S. Government. The FDA’s role is gatekeeper, not development driver, yet dealing with them may mean accepting a lot about how FDA expects to see things done, and FDA DOES regulate the production process of drugs made in the United States. It is common for other government agencies to participate as co-applicants to the FDA, with private entities. In the Trump Administration, Operation Warp Speed served as that development driver where vaccines were concerned. Under Biden, OWS and the White House Coronavirus Task Force have been combined, becoming the White House COVID-19 Response Team (with some former OWS functions reverting to NIH or other HHS or DoD departments).

Novavax still intends to apply for Emergency Use Authorization in the U.S., toward the end of this year. The company may be in a good position to produce future boosters as more information about variants becomes available, and may be able to combine such a booster with a flu vaccine so both can be administered as a single shot. Meanwhile, the world is hungry for a proven, effective vaccine, so to them the Biden Administration seems to be saying ‘here, take this one’. It’s true that the easier storage and shipping requirements of Novavax lend themselves better to worldwide distribution than do the deep-freeze requirements of many others. Having said that, there may be unused, perishable supply of other vaccines in the U.S. that will go to waste if not shared in a timely manner. WHO officials ask that we not wait.

Historical & Technical

Novavax got into the COVID-19 vaccine effort as a small entity with a limited mission for which it was well suited: produce a great vaccine. The Maryland company bought a Swedish company in 2013, bringing in-house production of an adjuvant key to their secret sauce. Their large-scale vaccine production experience, however, was very limited, so fulfillment was farmed out to partners in the U.S. and around the world. That means technology transfer, and as quality assurance issues inevitably have arisen, things have become messy.

COVID-19 vaccines can be thought of in four categories;

nucleic acid (to which the mRNA type belongs),

viral vector (describing J&J and AstraZeneca vaccines),

attenuated or inactivated whole virus,

protein subunit (Novavax and other candidates).

All these types have been in evidence in some form among influenza vaccines, so only the most recent mRNA technology is really new. The protein subunit type debuted in the 1980s as an improvement to Hepatitis B vaccine, and was further developed in the 1990s in various applications to where there are a number of examples today.

Funding from the Coalition for Epidemic Preparedness Innovations (CEPI) fueled Novavax’ entry into the COVID-19 vaccine race. Their candidate employs full-length spike protein derived from infected moth cells, then recombined into groups of several chains joined together to form “glycoprotein nanoparticles” that medical lecturer Dr. Mobeen Syed compares to “edible arrangements”. A tree-bark-derived adjuvant helps stimulate an immune response by the recipient to the presence of these nanoparticles of spike protein.

Novavax NVX-CoV2372 has distinguished itself as the standout protein subunit COVID-19 vaccine by its strong performance in clinical trials. In addition to showing efficacy close to that of the mRNA vaccines, Novavax clinical trials have generated fewer reports of adverse reactions than other vaccine types. That is not surprising when one understands the differences among the categories, and is consistent with previous subunit vaccine experience. .At the close of a short video on its website, GAVI, The Vaccine Alliance, states, “It is likely that a mixture of different approaches will be needed in order to stop the global spread of the coronavirus, and end the pandemic.”

Meanwhile, media reports and messaging from health authorities in the U.S. have increasingly contained the two words “the vaccine”, clearly referring jointly to the Pfizer & Moderna mRNA shots, even while there are seven vaccines Emergency Use Listed by the World Health Organization:

Pfizer – BioNTech BNT162b2

Moderna mRNA-1273

Janssen / J&J Ad26.COV2.S

Covishield ChAdOx1-S

AstraZeneca AZD1222 (inclusive of SII Covishield)

Sinovac-CoronaVac

Sinopharm

Three others are ahead of Novavax for consideration, including the Russian Sputnik V, yet Novavax remains the first, but not the only, protein subunit type listed for consideration by the WHO. What concerns many is that Novavax, the company, has been missing its target dates for both applications and deliveries including some that nations, including Australia, were counting on. Other vaccine suppliers have missed fulfillment targets, but worrying signals have caused Novavax to focus on fulfilling contracts in India, Indonesia, and The Philippines while postponing their EUA application in the U.S. until at least October.

RNA vaccines seem to produce very different antibody levels

RNA vaccines seem to produce very different antibody levels – Ars Technica

We've tended to treat the RNA-based vaccines from Moderna and Pfizer/BioNTech as functionally equivalent. They take an identical approach to producing immunity and have a very similar set of ingredients. Clinical trial data suggested they had very similar efficacy—both in the area of 95 percent.

So it was a bit of a surprise to have a paper released yesterday indicating that the two produce an antibody response that's easy to distinguish, with Moderna inducing antibody levels that were more than double that seen among people who received the Pfizer/BioNTech shot. While it's important not to infer too much from a single study, this one was large enough that the results are likely to be reliable. If so, the results serve as a caution that we might not want to base too many of our expectations on relatively crude measures of antibody levels.

The new study

The work itself was remarkably simple. A Belgian medical center was vaccinating its staff and asked for volunteers willing to give blood samples. Samples were taken both prior to vaccination and six to 10 weeks after, with the levels of antibody specific to the SARS-CoV-2 spike protein tested at both points. About 700 participants received the Moderna vaccine, while roughly 950 took the one from Pfizer/BioNTech.

With the data in hand, the researchers simply compared the levels of antispike antibodies in the different groups. One thing this revealed is that those who had been infected prior to the vaccination developed a much higher response than the other participants, with over five times the amount of antibodies following vaccination.

But the notable surprise was that the Moderna vaccine generated a stronger response than the Pfizer/BioNTech version. In terms of units of antibody per millilitres of blood sample, the difference was 3,836 to 1,444, with confidence intervals that didn't come close to overlapping. In other words, it's a statistically significant difference in a sufficiently large sample that it's unlikely to be by chance.

That said, there are a couple of caveats. One is that, while the medical center was likely able to store and administer the vaccines appropriately, they were at the end of a complicated production and distribution network, and there is a chance that something happened to one of the vaccines before it made it to the clinic. A simple replication would sort this out quickly.

What to make of it?

The other important caveat is that the researchers behind the study simply measured the total levels of antibody that stuck to the spike protein. Only a subset of these will be what are termed neutralizing antibodies, which stick to spikes in a way that interferes with the protein's ability to interact with cells and insert the virus' genome. Measuring neutralizing antibodies is much more difficult, so most studies do what this one has.

But it's technically possible that, despite the differences in total antibodies, both vaccines generated similar levels of neutralizing antibodies—something else an additional study could sort out. This would be consistent with the vaccines' generally similar levels of protection, as protection seems to correlate with neutralizing antibody levels.

While we wait for data to help sort this out, it's worth considering whether we might be placing a little too much emphasis on antibody levels in our decision-making. Right now, arguments about the need for boosters are based in part on the fact that antibody levels drop over time, even though that's a normal consequences of the shift away from a response to an active infection and toward a functional immune memory of that infection. And the efficacy of a booster is being based in part on the fact that it restores high levels of antibody—even though that's exactly what should happen when the immune memory cells are activated by re-exposure to the spike protein.

As with these new results, these results should be approached with caution, since we don't fully understand how these changes in antibody level correlate with protection.

JAMA, 2021. DOI: 10.1001/jama.2021.15125 (About DOIs).

THH pay attention

Sterically confined rearrangements of SARS-CoV-2 Spike protein control cell invasion

Sterically confined rearrangements of SARS-CoV-2 Spike protein control cell invasion

SARS-CoV-2 entry mechanism through membrane fusion is regulated by the spike protein glycosylation state.

elifesciences.org

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is highly contagious, and transmission involves a series of processes that may be targeted by vaccines and therapeutics. During transmission, host cell invasion is controlled by a large-scale (200–300 Å) conformational change of the Spike protein. This conformational rearrangement leads to membrane fusion, which creates transmembrane pores through which the viral genome is passed to the host. During Spike-protein-mediated fusion, the fusion peptides must be released from the core of the protein and associate with the host membrane. While infection relies on this transition between the prefusion and postfusion conformations, there has yet to be a biophysical characterization reported for this rearrangement. That is, structures are available for the endpoints, though the intermediate conformational processes have not been described. Interestingly, the Spike protein possesses many post-translational modifications, in the form of branched glycans that flank the surface of the assembly. With the current lack of data on the pre-to-post transition, the precise role of glycans during cell invasion has also remained unclear. To provide an initial mechanistic description of the pre-to-post rearrangement, an all-atom model with simplified energetics was used to perform thousands of simulations in which the protein transitions between the prefusion and postfusion conformations. These simulations indicate that the steric composition of the glycans can induce a pause during the Spike protein conformational change. We additionally show that this glycan-induced delay provides a critical opportunity for the fusion peptides to capture the host cell. In contrast, in the absence of glycans, the viral particle would likely fail to enter the host. This analysis reveals how the glycosylation state can regulate infectivity, while providing a much-needed structural framework for studying the dynamics of this pervasive pathogen.

Discussion

The ongoing COVID-19 pandemic requires the rapid identification of molecular factors that enable infection. A necessary step during infection involves virus/cell membrane fusion, which is mediated by a major conformational change of the Spike protein. Here, we propose a mechanism where, after cleavage and dissociation of S1, sufficient time has to be made available for the fusion peptides to reach the cell membrane, before the conformational change in S2 can complete. Using all-atom models with simplified energetics, we have shown how the steric composition of post-translational modifications may introduce the delay necessary for such a mechanism to be utilized. This glycan-induced pause appears to allow for an extended window during which the fusion peptides may search for the host cell (Figure 6). In simulations that did not include glycans, the Spike protein was most likely to adopt the postfusion configuration without extending the fusion peptides towards the host. Thus, in the glycan-free case, the protein can bypass the sterically-caged intermediate, leading to failed attempts to capture the host cell. These findings suggest an interesting theoretical prediction that the precise glycan composition is a critical factor that determines transmissibility of SARS-CoV-2.

The current predictions suggest that the steric composition of the Spike protein and glycans can guide the global dynamics of host-membrane capture. While these results are intuitive, it is possible that non-specific stabilizing interactions (i.e. not found in the pre, or post, fusion conformations) can have a notable influence on the rearrangement. For example, there may be specific long-lived non-native interactions that can transiently maintain the orientation of the HG region and facilitate FP capture of the host. Another limitation of the current analysis is that our model describes interactions between the Spike and effective membrane regions in terms of a short-range effect. If long-range electrostatic interactions dominate the FP-membrane association process, then it is possible that an alternate sequence of events may be observed. Finally, another avenue for further study would be to consider so-called ‘multi-basin’ structure-based models (Whitford et al., 2007). In such approaches, each element of the Spike protein would have interactions that stabilize both the pre and postfusion conformations. This would allow one to identify the influence of competing stabilizing interactions that may impede the ‘downhill’ dynamics of the current model. For example, introducing prefusion contacts in the HR2 region would likely delay entry of HG into the cage. Similarly, prefusion interactions could extend the time required for the FPs to initially dissociate from S2. With these open questions in mind, it will be interesting to see the extent to which various factors can enhance or attenuate the steric signatures that are described in the current study. In this context, the presented simulations provide a foundation for understanding and quantifying the relative contributions of each biophysical factor during this large-scale motion.

With the range of possible contributors to Spike protein dynamics, there are clear opportunities for novel experiments to reveal the precise influence of glycosylation on Spike protein mediated cell entry. To test the predictions of the current study, one may consider applying site-specific mutations, in order to inhibit glycan binding at individual residues. These altered Spike protiens could then be integrated into pseudovirus particles (Yang et al., 2020), which would allow one to measure the impact of specific glycans on the ability of the Spike to associate with a cell. If sterics dominate the dynamics, as predicted by the structure-based model, then mutations to HG glycan sites should significantly reduce the probability of membrane capture.

In addition to providing immediate insights into the influence of glycans on Spike protein dynamics, the current simulations establish a foundation for experimentally and theoretically investigating other factors that may influence cell invasion. To give one example, the presented models may be extended to account for electrostatic and solvation effects. With ongoing advances in high-performance computing, combined with the relatively low computational cost associated with these models, many variations may be explored in the coming months that will help elucidate the full range of factors that control this deadly pathogen.

This study screams TREAT EARLY and TREAT ALL!!!!!

Microbial signatures in the lower airways of mechanically ventilated COVID-19 patients associated with poor clinical outcome

Microbial signatures in the lower airways of mechanically ventilated COVID-19 patients associated with poor clinical outcome - Nature Microbiology

Analysis of lower respiratory tract microbiome of mechanically ventilated COVID-19 patients rules out a role for secondary respiratory infections as drivers of…

www.nature.com

Abstract

Respiratory failure is associated with increased mortality in COVID-19 patients. There are no validated lower airway biomarkers to predict clinical outcome. We investigated whether bacterial respiratory infections were associated with poor clinical outcome of COVID-19 in a prospective, observational cohort of 589 critically ill adults, all of whom required mechanical ventilation. For a subset of 142 patients who underwent bronchoscopy, we quantified SARS-CoV-2 viral load, analysed the lower respiratory tract microbiome using metagenomics and metatranscriptomics and profiled the host immune response. Acquisition of a hospital-acquired respiratory pathogen was not associated with fatal outcome. Poor clinical outcome was associated with lower airway enrichment with an oral commensal (Mycoplasma salivarium). Increased SARS-CoV-2 abundance, low anti-SARS-CoV-2 antibody response and a distinct host transcriptome profile of the lower airways were most predictive of mortality. Our data provide evidence that secondary respiratory infections do not drive mortality in COVID-19 and clinical management strategies should prioritize reducing viral replication and maximizing host responses to SARS-CoV-2.

Discussion

The samples used in this investigation were obtained during the first surge of cases of COVID-19 in New York City, and management reflected clinical practices at that time. Among the differences with current therapeutic approaches in COVID-19 patients, corticosteroids and remdesivir, two medications that likely affect the lower airway microbial landscape, were rarely used during the first surge. Other medications, such as antibiotics and anti-inflammatory drugs, could affect our findings, and we therefore considered them as potential confounders. However, the use of these medications was not found to be associated with clinical outcome. Of note is that although our institutions were responding in ‘surge mode’, both the Long Island and Manhattan campuses did not suffer from shortages in medical staff, supplies or equipment and the decision to start MV did not differ from the standard of care. The cross-sectional study design precluded evaluation of the temporal dynamics of the microbial community or the host immune response in this cohort, which could have provided important insights into the pathogenesis of this disease. Performing repeated bronchoscopies without a clinical indication would be challenging in these patients, and other, less invasive, methods might need to be considered to study the lower airways at earlier time points and serially over time in patients with respiratory failure. It is important to note that there were no statistically significant differences in the timing of sample collection across the three outcome groups. Evaluation of microbial signals at earlier time points in the disease process might also be important to identify changes occurring prior to use of broad-spectrum antimicrobials. Also, the presented data from lower airway samples are restricted to those subjects for whom bronchoscopy was performed as part of their clinical care. Thus, the culture-independent data are biased towards patients who, while critically ill with COVID-19, were not representative of the extremes in the spectrum of disease severity. Investigations focusing on early sample collection time points may be warranted to include subjects on MV with early mortality or early successful discontinuation of MV.

In summary, we present here the first evaluation of the lower airway microbiome using a metagenomic and metatranscriptomic approach, along with host immune profiling, in critically ill patients with COVID-19 requiring invasive MV. The RNA metatranscriptome analysis showed an association between the abundance of SARS-CoV-2 and mortality, consistent with the signal found when viral load was assessed by targeted rRT–PCR. These viral signatures correlated with lower anti-SARS-CoV-2 spike IgG and host transcriptomic signatures in the lower airways associated with poor outcome. Importantly, both through culture and NGS data, we found no evidence for an association between untreated infections with secondary respiratory pathogens and mortality. Together, these data suggest that active lower airway SARS-CoV-2 replication and poor SARS-CoV-2-specific antibody responses are the main drivers of increased mortality in COVID-19 patients requiring MV. The potential role of oral commensals such as M. salivarium needs to be explored further. It is possible that M. salivarium can impact key immune cells, and it has recently been reported at a high prevalence in patients with ventilator-acquired pneumonia44. Critically, our finding that SARS-CoV-2 evades and/or derails effective innate/adaptive immune responses indicates that therapies aiming to control viral replication or induce a targeted antiviral immune response may be the most promising approach for hospitalized patients with SARS-CoV-2 infection requiring invasive MV.

Vaccine Shakeup at FDA as Key Leadership Resigns, Leaving A Potential Void Impacting POTUS Vaccination Program

Vaccine Shakeup at FDA as Key Leadership Resigns, Leaving A Potential Void Impacting POTUS Vaccination Program

Marian Gruber, director of the U.S. Food and Drug Administration (FDA) Vaccine Research Review Bureau, and Phil Krause, deputy director, plan on stepping

trialsitenews.com

Marian Gruber, director of the U.S. Food and Drug Administration (FDA) Vaccine Research Review Bureau, and Phil Krause, deputy director, plan on stepping down this October and November, respectively. The senior Agency executives responsible for reviewing the recent Pfizer COVID-19 vaccine submission are on their way out, a spokesperson confirmed today, August 31, 2021.

Are the prominent leaders departing due to federal-level politics? Are they concerned that forces from the White House to the Centers for Disease Control (CDC) are overstepping their reach in what has become a politicized pandemic—both with the previous POTUS and Biden, who has attempted to isolate and shame those that aren’t vaccinated. The CDC and White House need to stay in their freeway lane.

Marion Gruber, PhD, director of the FDA’s Office of Vaccines Research & Review has been working for the Gold Standard agency or 32 years—she will depart October 31, while Phil Krause will depart in November, reports Peter Marks, MD, PhD, head of the Center for Biologics Evaluation and Research.

A former FDA insider informed research news site Endpoints that the two were not happy about how the review processes unfolded as of late, with the CDC and its Advisory Committee on Immunization Practices apparently operating out of their freeway line.

This is the purview of the FDA, and if that information is true, then the agency, which TrialSite reports already has sunk to new lows in terms of popular perception and trust levels, faces perhaps even more of a forthcoming crisis.

CDC, White House—Keep Out

Moreover, the Biden White House’s aggressive push to accelerate boosters shots appears to have further upset the veterans who understand the importance of separation and regulatory firewalls.

TrialSite has emphasized the accelerated nature of the FDA approval of the Pfizer vaccine, lack of transparency, and disregard for standard processes, although the agency claims to the contrary.

Rick Bright, a former director of the U.S. Department of Health and Human Services’ Biomedical Advanced Research and Development Authority (BARDA), tweeted today, “These two are the leaders for biologics (vaccine) review in the U.S. They have a great team, but these two are the true leaders of CBER. A huge global loss if they both leave.”

According to Bright, “Dr. Gruber is much more than the Director. She is a global leader. Visionary mastermind behind global clinical regulatory science for flu, Ebola, Mers, Zika, Sars-cov-2, many others.”

Under Investigation

TrialSite reported recently that due to the rushed and possibly inappropriate approval of Biogen’s recent Alzheimer’s disease drug, the FDA will now be subject to an Office of Inspector General (OIG) investigation into processes and practices. Are agency staff getting too close to industry? TrialSite suggests many lament a growing “regulatory capture,” that is, undue influence of industry over the regulators.

In a major blow to vaccine efforts, senior FDA leaders stepping down

Two of the FDA's most senior vaccine leaders are exiting from their positions, raising fresh questions about the Biden administration and the way that it's…

endpts.com

Quote from THHuxleynew

18.5 per million doses given among people aged 18 to 24 after their second Pfizer dose and 20.2 per million for that age group among Moderna second dose recipients.

The usual THH FUD trick!

--> use wrong data Moderna instead of Pfizer to claim less damage. And not adding 18.5 +20.2 about 40

as not jabs count. May be you know it too you can only die once ... so we counted patients.

Quote from THHuxleynew

mRNA vaccines induce memory B-cell response.

Nobody denies this. But these B-cells are of no use at all. May be you missed to read some papers we linked above. But I do not teach spin doctors its a waste of time.

Quote from THHuxleynew

However it would be strange if they provided no protection. Even for elderly people.

The protection is just proportional to the induced (almost) monoclonal antibodies. Here we have correlation and causation!

Quote from Wyttenbach

The usual THH FUD trick!

--> use wrong data Moderna instead of Pfizer to claim less damage. And not adding 18.5 +20.2 about 40

as not jabs count. May be you know it too you can only die once ... so we counted patients.

Ok, apologies, I thought you were talking mRNA vaccines overall, my mistake. Why do you think Pfizer is worse for pericarditis than Moderna? The rumour seems to be the reverse - Moderna has high dose of mRNA so any reactions likely larger there? Anyway why cherry-pick just one of these - I thought you were against mRNA vaccines?

I was compensating for the 2 jabs one patient thing, and the fact that 2nd dose normally carries most of the pericarditis risk.

I'm mystified why you think I'm posting FUD? How do my posts make you afraid?

Quote from THHuxleynew

The EU's drug regulator said on July 9 that five people had died due to the heart side effect after receiving either of the two mRNA vaccines in the European Economic Area, all of whom were elderly or had other diseases. More than 200 million mRNA doses have been administered in the region.

I did not know about this report. Let me correct my statement that the NZ person was the first confirmed death from the mRNA vaccines.

I have been watching the U.S. stats, not the European ones. When I last checked there were no confirmed reports of deaths in the U.S. from the mRNA vaccines.

As I said, when you give billions people a teaspoon of salt, some will probably die from it. Anything is toxic at some level, for some fraction of the population. So, as hard-hearted as it sounds, a few deaths from the mRNA vaccines are nothing to be concerned about. If some pattern emerges and we discover that people with certain conditions, comorbidities, or in some age group are vulnerable at a rate something like 1 per million, then those people should be little extra careful. Instead of hanging around for 15 minutes after getting a vaccine, perhaps they should stay for an hour. Or, if the deaths occur within days, they should stay in close touch with a hospital and have someone monitor their condition.

On Death’s Doorstep:’ Ohio Judge Compels Hospital to Treat a Severe COVID-19 Patient with Ivermectin After Failure of Sanctioned Protocol

'On Death's Doorstep:' Ohio Judge Compels Hospital to Treat a Severe COVID-19 Patient with Ivermectin After Failure of Sanctioned Protocol

Yet another judge entered the COVID-19 ivermectin-based fray, this time siding with the patient. Butler County Common Pleas Judge Gregory Howard ordered

trialsitenews.com

Yet another judge entered the COVID-19 ivermectin-based fray, this time siding with the patient. Butler County Common Pleas Judge Gregory Howard ordered West Chester Hospital, part of the University of Cincinnati network, to follow the instructions of the plaintiff’s physician and administer the antiparasitic drug ivermectin to a 51-year old Jeffrey Smith. In the ICU for several weeks with severe COVID-19—the hospital’s protocol (Remdesivir, plasma, and steroids) were failing. Mr. Smith’s wife Julie Smith found attorney Ralph Lorigo—profiled in TrialSite—and thereafter, with his help, filed a complaint to compel the hospital to treat her husband with ivermectin after the failure of the hospital’s COVID-19 protocol. Unlike another recent case, here, the plaintiffs appeared to score a victory as Judge Howard compelled the hospital to care for the patient following the recommendation of the family’s chosen physician.

TrialSite shares a link to the original coverage by Jake Zuckerman with the Ohio Capital Journal.

Mr. Smith ‘On Death’s Doorstep’

That’s how close Jeffrey Smith is to the end at West Chester Hospital. According to the Ohio Capital Journal, on July 9th, Mrs. Smith tested positive with SARS-CoV-2, the virus behind COVID-19. With a worsening condition, Smith was admitted to the ICU on July 15th. That action triggered the West Chester Hospital COVID-19 protocol, including Remdesivir, convalescent plasma and steroids.

The use of Remdesivir has become controversial in many places worldwide. Why? Because the World Health Organization (WHO) Solidarity trial led to the conclusion that the drug provides no meaningful benefit. Moreover, several researchers—ironically one involving the University of Cincinnati—for which West Chester Hospital is an affiliate—indicated the potential for health risks with remdesivir. The antiviral drug is associated with a range of safety issues.

Moreover, the hospital administered convalescent plasma, which has been controversial. And while some positive data was detected earlier in the pandemic, some studies also disappointed. As reported by TrialSite, the COVID-19 study results show the use of plasma and standard of care Remdesivir made no difference in patient outcomes in this particular study.

Although reports are that the hospital’s protocol may have had some impact for a few days, by July 27th, 12 days later, his condition severely worsened, indicating that in this case, the hospital’s protocol failed. The hospital then sedated and intubated the patient, hooking him up to a ventilator by August 1st. After that, he was placed in a “medically induced coma,” leading his wife to declare in the lawsuit affidavit, “My husband is on death’s doorstep; he has no other options.” With a probability of less than 30% now, Mrs. Davis turned to attorneys in a quest to save her husband’s life.

Before summarizing the case, TrialSite reminds the reader that the pandemic has triggered unprecedented federal centralization over healthcare. While proponents defend that the pandemic is like wartime and the federal government must centralize, consolidate and direct action to protect the homeland, others suggest that this pathogen is complex, and some of the treatments the FDA have approved aren’t accepted at all by the World Health Organization (WHO), such as Remdesivir. This group suggests more flexibility, the importance of care provider influence, etc.

Brief Overview

As Jeffrey Smith’s condition worsened to the point that the hospital placed him into a “medically induced coma,” his wife had really no options and would otherwise certainly lose her husband. That’s the driver behind retaining a lawyer and filing a lawsuit against the hospital to compel them to act in saving Smith’s life.

Mrs. Smith, at some point, found Ohio Pulmonologist Dr. Fred Wagshul identified in the lawsuit as “one of the foremost experts on using Ivermectin in treating COVID-19.”

After the hospital outright rejected the suggestion (possibly related to federal money directed to the facility), Ms. Smith filed the action.

The Order

Judge Gregory Howard made his decision, indicating his interpretation of the facts and application of the law, ordering the hospital to administer to Mr. Smith 30 mg of ivermectin for three weeks. The judge declared that in response to the plaintiff’s demand to compel the defendant to follow the instructions of Dr. Wagshul –provider of the ivermectin prescription.

Call to Action: For a more detailed read, follow the link to the actual filings.

J smith ivermectin complaint

www.documentcloud.org

Quote from Fm1

On Death’s Doorstep:’ Ohio Judge Compels Hospital to Treat a Severe COVID-19 Patient with Ivermectin After Failure of Sanctioned Protocol

I commented on this elsewhere --

Yes. That is one case. You may find a few others. There are 88,000 counter-examples per week. Many people who want ivermectin are getting it, and many doctors are prescribing it.

Do you think it is a good idea to force doctors to take medical steps, prescribe medication, or perform surgery against their own better judgement? That would violate their oaths. Do you think we should let judges overrule the professional opinions of doctors? Would you also let a judge order a pilot to take off in bad weather, even if the pilot thinks it is dangerous? Would you let a judge order that a bridge remain open, even though civil engineers and inspectors conclude that the bridge is on the verge of collapsing and it is extremely dangerous?

If this spouse wants ivermectin to be used, but the hospital doctors and administrators do not agree with this medical decision, the spouse should find some other doctors. The legal system should not be used to overrule or interfere with life-and-death decisions by professionals.

Ivermectin and suppression

Quote from JedRothwell

Do you think we should let judges overrule the professional opinions of doctors?

Doctors in a hospital setup have no professional opinion when the hospital management dictates how to treat (make money with) CoV-19 patients. Either they follow or quit.

Quote from JedRothwell

If you have some knowledge of modern cars you know they are difficult to fix without training, computers, and certified parts.

This is getting off topic . . . but if you don't know anything about modern cars, let me describe things. In the 1960s, a Volkswagon was wonderfully simple and robust. A high school kid could fix one. I didn't, but my friends fixed an ancient one, and it kept running until it finally burst into flames years later. It had a mechanical distributor. With a strobe light and a screwdriver you could fix it. The speedometer was a magnet and needle, invented in 1888. The parts were few, and available anywhere. If the door did not close, you could fix it with a hammer. Of course the car did not have a single digital gadget.

Nowadays, cars have more computers than the Apollo rocket. To diagnose or fix them, you first talk to the computers. The parts are made to much tighter standards. The motors are not assembled by the hands of man, but by robots. You can tell at a glance that no human could have assembled such a thing. There are some parts that a high school kid can fix. A shade tree mechanic with the right tools can refurbish old cars. But you cannot do as much as you used to. There are good reasons for these changes. Cars are far more fuel efficient, less polluting, safer, and they last longer. It is easier to fix them when the computer tells you what the problem is. Still, it is sort of a shame kids cannot fix them . . .

Along the same lines, I used to have a one-page table listing every op code of the Z80 processor, which was a thing of elegant beauty. I knew every single operating system call in Data General computers. That is to say, everything the computer could do, from setting the clock to dispatching a background task. Nowadays, an Intel processor must have hundreds of op codes. I have no idea how many. They have a whole bunch just to help ensure security. (They don't seem to work well, do they?) Windows has over 2,000 system calls. For example, it seems there are six kinds of floating point numbers, and dozens of calls to them:

Math and floating-point support

Describes floating-point support in the Microsoft Universal C Runtime library (UCRT)

docs.microsoft.com

Modern technology works better because it is more complicated, but that make it hard to understand. It makes it hard for you to judge what's what, and how the CDC evaluates the VAERS database. They use AI tools which are so complex, no human can understand the details. A modern AI multilevel neural network is the most complex thing ever made. The largest ones in 2018 had 160 billion parameters.

Biggest Neural Network Ever Pushes AI Deep Learning

Digital Reasoning has trained a record-breaking artificial intelligence neural network that is 14 times larger than Google's previous record

spectrum.ieee.org

Researchers recently developed a multiprocessor computer on a single giant integrated circuit with 850,000 processors. No one could begin to understand in detail what these things are doing.

The World’s Largest Computer Chip

In the race to accelerate A.I., the Silicon Valley company Cerebras has landed on an unusual strategy: go big.

www.newyorker.com

Homepage | Cerebras

cerebras.net

Airlines May Start Banning Cloth Masks

https://www.newsmax.com/amp/health/health-news/covid-masks-cloth-surgical/2021/09/01/id/1034624/

The friendly skies are becoming not-so-friendly to passengers wearing cloth masks. Several airlines overseas are already banning cloth masks and requiring that travelers wear surgical masks, FFP2 masks, KN95 or N95 masks without valves on flights.

According to Fortune, Finnish airline Finnair and Germany’s Lufthansa are two of the many European carriers shunning cloth masks. So far, no American airline has mandated the more efficient face coverings but with the Delta variant spreading, the policies may change.

While cloth masks have been best-sellers during the pandemic, allowing people to make a fashion or even political statement with their masks, the Centers for Disease Control and Prevention say they are not as protective as other filters.

The filtration effectiveness of cloth masks is generally lower than that of medical masks and respirators; however, cloth masks may provide some protection if well designed and used correctly,” said the CDC in a statement last year.

When wearing a cloth mask, two layers are better than one. According to Business Insider, research has shown that that a two-layered fabric mask is superior to a single-layered cloth face covering, so doubling up is recommended. Experts even suggest using three layers to help filter out potentially infectious respiratory droplets and aerosols. A study in April determined that when two layers of 600 thread-count cotton were added to a layer of another common fabric such as silk or chiffon, the mask was even more efficient in filtering out particles. However, the study authors warned that if any mask is ill-fitting and has gaps, this can result in a 60% decrease in filtration efficiency.

Experts have noted that it is important to don a good quality mask to stop 99% of virus-laded droplets from being transmitted into the air, according to the New York Daily News. Researchers from Duke University found that the best protection was offered by the N95 masks without a valve, followed by three layered surgical masks.

U.S. airlines do have some mask restrictions, says Fortune. Bandanas and scarves are not acceptable forms of masks, nor are ski masks and balaclavas. Masks are required in all airports, airplanes, and other forms of public transportation until at least January 2022.

As jed point out, not just anyone can fix the new designs of cars or just about anything today but we still have time - to learn the old ways

flccc update for delta..GAMMA.

definitely Marik and Kory have an interest in Flavio's androgenic mechanism

+ spiranolactone,,,, needs a prescription

povidone-iodine mouth wash 2-3x daily

FLCCC Weekly Update August 25, 2021 with Dr. Kory, Dr. Marik, and our new FLCCC Clinical Advisor Dr. Flávio Cadegiani

This week's FLCCC Weekly Update hosted by Betsy Ashton with Dr. Pierre Kory, Dr. Paul Marik, and our new addition to the FLCCC team, Dr. Flávio Cadegiani.

odysee.com

Joe Rogan Says He Has COVID-19 And Has Taken The Drug Ivermectin

NPR Cookie Consent and Choices

Joe Rogan, the mega-popular podcast host who has suggested that young, fit people don't need to get the COVID-19 vaccine, has announced he tested positive for the virus, but is feeling fine thanks to a cocktail of unproven medical treatments.

In an Instagram video, the 54-year-old host of the Joe Rogan Experience, said he felt "very weary" on Saturday and got tested for COVID-19 the following day.

"Throughout the night I got fevers, sweats, and I knew what was going on," Rogan told his 13.1 million followers.

After the diagnosis, he said he "immediately threw the kitchen sink at it."

Rogan says he took a drug the FDA urges people not to use

That included taking ivermectin, a deworming veterinary drug that is formulated for use in cows and horses. While a version of the drug is sometimes prescribed to people for head lice or skin conditions, the formula for animal use is much more concentrated. The Food and Drug administration is urging people to stop ingesting the animal version of the drug to fight COVID-19, warning it can cause nausea, vomiting, abdominal pain, neurologic disorders and potentially severe hepatitis requiring hospitalization.

Rogan added that his treatments also included monoclonal antibodies, Z-pack antibiotics, and a vitamin drip for "three days in a row."

"Here we are on Wednesday, and I feel great," he said.

Rogan has drawn fire for his comments around the vaccine

Rogan has won legions of dedicated listeners by courting controversy on his show. Last October, he came under fire for interviewing far-right conspiracy theorist Alex Jones on his Spotify show. More recently, he faced criticism after saying that young and otherwise healthy people don't need a COVID-19 vaccine

"People say, do you think it's safe to get vaccinated? I've said, yeah, I think for the most part it's safe to get vaccinated. I do. I do," Rogan said in an April 28 episode of the podcast.

"But if you're like 21 years old, and you say to me, should I get vaccinated? I'll go no. Are you healthy? Are you a healthy person?"

"If you're a healthy person, and you're exercising all the time, and you're young, and you're eating well," Rogan continued, "like, I don't think you need to worry about this."

He later explained that he is not "an anti-vax person," and joked that he is not "a respected source of information, even for me."

Merck Progresses with Molnupiravir Household Contacts Study for PEP: MOVE

Merck Progresses with Molnupiravir Household Contacts Study for PEP: MOVE

Select pharmaceutical companies race to secure approval of a safe and effective antiviral treatment for early-onset COVID-19. Merck, in partnership with

trialsitenews.com

Select pharmaceutical companies race to secure approval of a safe and effective antiviral treatment for early-onset COVID-19. Merck, in partnership with Ridgeback Biotherapeutics, now progresses with its MOVE—AHEAD study evaluating molnupiravir, an investigational oral antiviral therapeutic, for the prevention of COVID-19 infection. The global study is enrolling individuals who are at least 18 years of age and reside in the same household as someone with laboratory-confirmed SARS-CoV-2 infection with symptoms. Known as a household contracts trial, the American pharmaceutical company seeks to determine the ability for the drug to be used as a Post-Exposure Prophylaxis. Meanwhile, in the Philippines, Merck’s comments combined with those from the apex health agencies in that country contribute to growing media doubts about ivermectin, the low-cost generic drug also used in clinical trials there as well as off-label by some community efforts.

Merck has received $356 million from the U.S. government and has secured a $1.2 billion procurement contract should this investigational product be effectively authorized under emergency use authorization (EUA) or approved.

The Study

The MOVe-AHEAD clinical trial represents Merck’s contacts-focused study. That is, the sponsor investigates the efficacy and safety/tolerability of the study drug in adults who reside with a person infected with COVID-19. Merck proposes that their drug is superior to placebo in preventing laboratory-confirmed COVID-19 infection through day 14 in participants who don’t have confirmed or suspected COVID-19 at the time of screening.

The safety and efficacy of molnupiravir are also currently being evaluated in Part 2 of the ongoing MOVe-OUT trial, which is a global Phase 3, randomized, placebo-controlled, double-blind, multi-site study of non-hospitalized adult patients with laboratory-confirmed mild to moderate COVID-19 and at least one risk factor associated with poor disease outcomes. Data from the study is expected in the second half of 2021.

MOVe-AHEAD Study

MOVe-AHEAD (MK-4482-013) (NCT04939428) is a Phase 3, multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of orally administered molnupiravir compared to placebo in preventing the spread of SARS-CoV-2, the virus that causes COVID-19, within households. The trial will enroll approximately 1,332 participants who will be randomized to receive either molnupiravir (800 mg) or a placebo orally every 12 hours for five days. The study will enroll participants who are at least 18 years of age and currently residing in the same household with someone who received a positive test for SARS-CoV-2, has at least one sign or symptom of COVID-19 and has not had those signs and symptoms for more than five days. Participants are not eligible for the trial if they have received the first dose of a COVID-19 vaccine more than seven days prior to enrollment, have previously had COVID-19 or are showing any signs or symptoms of COVID-19.

The trial’s primary endpoints include:

The percentage of participants with COVID-19 (laboratory-confirmed SARS-CoV-2 infection with symptoms) through Day 14.

The percentage of participants with an adverse event.

The percentage of participants who discontinued study intervention due to an adverse event.

The trial is being conducted globally in countries including Argentina, Brazil, Colombia, France, Guatemala, Hungary, Japan, Mexico, Peru, Philippines, Romania, Russia, South Africa, Spain, Turkey, Ukraine, and the United States.

Vaccine-Centric Strategy Not Sufficient

Already, TrialSite has suggested that the National Institutes of Health (NIH) and other health agencies understand that a vaccine-centric strategy is not sufficient to transcend this pandemic. The NIH is placing over $3 billion into antivirals. In fact, Dr. Nick Kartsonis, senior vice president, vaccines and infectious diseases, clinical research, Merck Research Laboratories, commented, “As the pandemic continues to evolve and surges are being reported in many places around the world, it is important that we investigate new ways to protect individuals exposed to the virus from becoming infected with symptomatic disease.” Merck’s executive continued, “If successful, molnupiravir could provide an additional option towards reducing the burden of COVID-19 on our communities.”

Offensive Against Ivermectin

Merck, a producer of Ivermectin, has been on the offensive against its own product. The pharmaceutical company has completely discounted dozens of studies from hundreds of investigators worldwide, declaring there is absolutely no evidence for any efficacy. The company even questioned its incredible safety record. TrialSite suggests Merck must clear out any possible generic competition, even if the drug isn’t proven yet.

In the Philippines, where Merck is conducting the molnupiravir study, Merck has been proactively talking down ivermectin which may be slowing down the momentum for that drug there, which was planned for a major clinical trial.

Reporting from the Philippines, Nina Cabaero shared recently that “recent statements by governments and the maker if ivermectin against the use of the drug in the treatment of coronavirus disease (COVID-19) patients should finally settle the matter.”

Identifying statements from Merck, the Philippines health departments and out of the U.S., the reports in this Southeast Asian nation don’t bode well for the economic drug as an option for COVID-19 in the Philippines.

About Molnupiravir

Molnupiravir (MK-4482/EIDD-2801) is an investigational, orally administered form of a potent ribonucleoside analog that inhibits the replication of multiple RNA viruses, including SARS-CoV-2, the causative agent of COVID-19. Molnupiravir has been shown to be active in several preclinical models of SARS-CoV-2, including for prophylaxis, treatment, and prevention of transmission, as well as SARS-CoV-1 and MERS. Molnupiravir was invented at Drug Innovations at Emory (DRIVE), LLC, a not-for-profit biotechnology company wholly owned by Emory University and is being developed by Merck & Co., Inc. in collaboration with Ridgeback Biotherapeutics. Since licensed by Ridgeback, all funds used for the development of molnupiravir have been provided by Wayne and Wendy Holman and Merck.

About Ridgeback Biotherapeutics

Headquartered in Miami, Florida, Ridgeback Biotherapeutics LP is a biotechnology company focused on emerging infectious diseases. Ridgeback markets EbangaTM for the treatment of Ebola and has a late-stage development pipeline that includes molnupiravir for the treatment of COVID-19. Development of molnupiravir is entirely funded by Ridgeback Biotherapeutics and Merck & Co., Inc. All equity capital in Ridgeback Biotherapeutics, LP originated from Wayne and Wendy Holman, who are committed to investing in and supporting medical technologies that will save lives. The team at Ridgeback is dedicated to working toward finding life-saving and life-changing solutions for patients and diseases that need champions.

About Merck

For over 130 years, Merck, known as MSD outside of the United States and Canada, has been inventing for life, bringing forward medicines and vaccines for many of the world’s most challenging diseases in pursuit of our mission to save and improve lives. We demonstrate our commitment to patients and population health by increasing access to health care through far-reaching policies, programs, and partnerships. Today, Merck continues to be at the forefront of research to prevent and treat diseases that threaten people and animals – including cancer, infectious diseases such as HIV and Ebola, and emerging animal diseases – as we aspire to be the premier research-intensive biopharmaceutical company in the world.

Brazilian viper venom may become tool in fight against COVID, study shows

Brazilian viper venom may become tool in fight against COVID, study shows

Brazilian researchers have found that a molecule in the venom of a type of snake inhibited coronavirus reproduction in monkey cells, a possible first step…

www.reuters.com

SAO PAULO, Aug 30 (Reuters) - Brazilian researchers have found that a molecule in the venom of a type of snake inhibited coronavirus reproduction in monkey cells, a possible first step toward a drug to combat the virus causing COVID-19.

A study published in the scientific journal Molecules this month found that the molecule produced by the jararacussu pit viper inhibited the virus's ability to multiply in monkey cells by 75%.

"We were able to show this component of snake venom was able to inhibit a very important protein from the virus," said Rafael Guido, a University of Sao Paulo professor and an author of the study.

The molecule is a peptide, or chain of amino acids, that can connect to an enzyme of the coronavirus called PLPro, which is vital to reproduction of the virus, without hurting other cells.

Already known for its antibacterial qualities, the peptide can be synthesized in the laboratory, Guido said in an interview, making the capture or raising of the snakes unnecessary.

"We're wary about people going out to hunt the jararacussu around Brazil, thinking they're going to save the world ... That's not it!" said Giuseppe Puorto, a herpetologist running the Butantan Institute's biological collection in Sao Paulo. "It's not the venom itself that will cure the coronavirus."

Researchers will next evaluate the efficiency of different doses of the molecule and whether it is able to prevent the virus from entering cells in the first place, according to a statement from the State University of Sao Paulo (Unesp), which was also involved in the research.

They hope to test the substance in human cells but gave no timeline.

The jararacussu is one of the largest snakes in Brazil, measuring up to 6 feet (2 meters) long. It lives in the coastal Atlantic Forest and is also found in Bolivia, Paraguay, and Argentina.

Quote from Fm1

Select pharmaceutical companies race to secure approval of a safe and effective antiviral treatment for early-onset COVID-19. Merck, in partnership with Ridgeback Biotherapeutics, now progresses with its MOVE—AHEAD study evaluating molnupiravir, an investigational oral antiviral therapeutic, for the prevention of COVID-19 infection.

This of course needs a lot of consulting and target bribing to get a failed drug through FDA.

Even more bribing will be needed to convince hospitals to use a 1000x more expensive drug when a better 10 cent pill is available..

Quote from Fm1

About Merck

For over 130 years, Merck, known as MSD outside of the United States and Canada, has been inventing for life, bringing forward medicines and vaccines for many of the world’s most challenging diseases in pursuit of our mission to save and improve lives. We demonstrate our commitment to patients and population health by increasing access to health care through far-reaching policies, programs, and partnerships. Today, Merck continues to be at the forefront of research to prevent and treat diseases that threaten people and animals – including cancer, infectious disease by cheating them with a barely working drug to make tons of money from idiots that still believe we are honest....