The Playground

  • WHO Pushes 70% Worldwide Vaccination Rate—Do They Have the Right Strategy? Time to Reevaluate the WHO Top-Down Approach


    WHO Pushes 70% Worldwide Vaccination Rate—Do They Have the Right Strategy? Time to Reevaluate the WHO Top-Down Approach
    While the fully vaccinated rate in India approaches 50%, the press from the world’s second-most populous nation touted a vaccination rate of 70%, an
    trialsitenews.com


    While the fully vaccinated rate in India approaches 50%, the press from the world’s second-most populous nation touted a vaccination rate of 70%, an unprecedented achievement. India’s rates of SARS-CoV-2 however, are on the rise again and the first turnaround and overcoming of the Delta variant-based surge seemingly had little to do with COVID-19 vaccination. Other nations have announced the 70% target and in fact, in India, about 70% of the population has received one dose of a COVID-19 vaccine but this doesn’t qualify as fully vaccinated. Yet, in a recent tweet by Prime Minister Narendra Modi, 70% of the adult population met the target. India’s 70% figure, if they can be believed, applies to adults. What is behind this 70% milestone that triggered the urgency for the press in India? The answer lies with the World Health Organization (WHO). That institution’s Independent Allocation of Vaccines Group (IAVG) has called for the achievement of 70% coverage with COVID-19 in all countries “as a global imperative.” Underlying this target are several assumptions, namely that vaccination stops or slows the transmission of mutants such as Delta and Omicron.


    Based on inputs on WHO’s website, underlying the 70% goal are drivers of equity and efficacy of fighting the COVID-19 pandemic. But why 70%? What is it about that number? Does some science exist establishing 70% as a number leading to herd immunity? How could that be when the world has discovered that SARS-CoV-2 herd immunity becomes elusive?


    TrialSite has reported on nations and territories where 100% vaccination (Gibraltar) and well over 80% vaccination rates (Iceland), (Seychelles), (Ireland), and (Israel) and many other examples led to just more infection and associated transmissibility based on variants such as Delta and Omicron.


    Yes, data does indicate the vaccines can and in fact do, inhibit more severe disease and mortality for at least a period. Data from health authorities such as the Ministry of Health in Israel and the U.S. Centers for Disease Control and Prevention (CDC) and others continue to show benefits of vaccination in reduction of hospitalization and mortality, yet those severe conditions aren’t distributed equally with SARS-CoV-2. The risks associated with severe disease and death correlate most of the time with known risk factors such as age and comorbidities. There are exceptions, however, and with just over 5.5 million deaths worldwide claimed as due to COVID-19, this pandemic of course ranks as the worst in a century.



    Given that vaccines have emerged as a health tool to protect against severe injury and death and that 90% of cases remain mild to asymptomatic, transmissibility continues with what are first-generation, leaky vaccines. Does a true economic cost-benefit analysis justify the current WHO approach—70% come hell or high water?


    What’s the WHO IAVG?

    Established just a year ago, WHO launched the IAVG to “validate and assess vaccine allocations recommended by WHO and GAVI’s Joint Allocation Taskforce (JAT) of COVAX.” As a reminder, GAVI, originally known as the “Global Alliance for Vaccines and Immunization” is a major player in global vaccine healthcare established in 2000 by national funders, including the United Kingdom and the United States. The Bill and Melinda Gates Foundation is a major financial backer.


    Working closely with WHO, the United Nations Children’s Fund (UNICEF), the World Bank, and vaccine producers, among others, TrialSite reports GAVI has been a key driver of the COVID-19 eradication of COVID-19 via vaccination drive with plans on implementing digital health cards and a global vaccine database as key tools to strengthen health systems.


    COVAX Fails

    WHO’s COVAX was established to ensure an equitable COVID-19 vaccine distribution model. TrialSite reported late in 2021 that the model to vaccinate the poorest countries failed miserably despite tens of billions allocated to COVAX via WHO and GAVI, along with participation by some vaccine producers.


    But why the failure? Was it shrewd industry monetization of the pandemic required by investors? While WHO founded the COVID-19 Vaccines Global Access (COVAX) initiative to ensure the equitable distribution and access of COVID-19 vaccines across the globe, the organization increasingly became entangled in a web of financial relationships, limiting its independence and objectivity.


    Backed by WHO, GAVI, the Coalition for Epidemic Preparedness Innovations (CEPI), the European Commission, and the French government, plus all the COVAX founding partners, COVAX’s facility mission involved the coordination of international resources enabling low-to-middle-income countries (LMICs) to access COVID-19 tests, therapies, and vaccines from Big Pharma and emerging biotech firms. Not in the plan whatsoever were bottom-up surprise developments such as the low cost, accessible repurposed drugs, given that 90% plus of SARS-CoV-2 infections continue to be mild and/or asymptomatic.


    By the summer of 2020, over 170 countries representing over 60% of the human population were participating in COVAX with a mission of equitable vaccine distribution. But the plans went in a southern direction. By the start of Q4 2021 with over 5.5 billion vaccines administered during the pandemic, 80% were administered in high-and upper-middle-income countries, reported WHO’s Director-General Dr. Tedros Adhanom Ghebreyesus. Tedros declared “Almost 90% of high-income countries have now reached the 10% target, and more than 70% have reached the 40% target. Not a single low-income country has reached either target.”


    Enter IAVG

    Again, WHO and GAVI’s Joint Allocation Taskforce (JAT) needed to better understand the COVAX situation—a validation and assessment of the equity targets for example, during this pandemic. IAVG was established to improve on what was a COVAX failure, at least partially. After all, COVAX was “envisioned to be the world’s primary distributor of COVID-19 vaccines with IAVG serving as an independent referee for needs-based allocation.”


    But according to the WHO, the rich countries such as America, the UK, and various players in Europe, Israel, and elsewhere largely “sidestepped COVAX, hoarding doses for their own populations and cutting deals directly with low-and middle-income countries.” This, of course, is one explanation for the COVAX COVID-19 vaccine equity distribution failure, or as WHO declares “….made the subsequent allocation decisions even more challenging.”


    But numerous forces and factors are involved, including Big Pharma lobby power and unfolding crony capitalism at the national and state level, incompetence, self-interest, and political dysfunctionality in wealthy national governments (don’t forget, America, the world’s richest country has the most deaths and a high case fatality rate comparatively speaking), and improper public health messaging that COVID-19 posed the exact same imminent danger to all population cohorts, creating outright panic as well as severe authoritarian-like policies in some Western governments.


    In some ways, during this pandemic, some Western governments strived to mimic China’s purported success staving off cases and deaths. TrialSite commented frequently over the past couple of years on the Chinese model during this pandemic frequently—known as the “Zero Tolerance” COVID-19 policy combined with mass vaccination starting in the summer of 2021.


    China’s model wasn’t free, however. It assumes vast export-based wealth combined with authoritarian, centrally planned governance, susceptible to corrupt practices from top to bottom to ensure the “Party” mission is complete. Much of the world doesn’t work this way despite WHO’s and even some Western places such as Australia’s attempt at replication.


    Does Central Planning Work or Global Health Care?

    WHO’s top-down, bureaucratic, yet industry intertwined approach has emerged as a serious force, and some could argue farce, in global healthcare —even posited by their website as a force for economic development in poor nations. Yet, the experience with Uttar Pradesh, India chronicled by this independent online media platform offers one example of how local or regional measures in LMICs are often superior for addressing health care contagion.


    After all, healthcare even in the richest nations such as the United States has always been a localized endeavor. The emergence of the Delta variant in India wreaked havoc there and in many other nations. The turnaround that occurred in India’s most populated state was praised by WHO as a model local public health strategy.


    While WHO advocated and provided testimony to notable regional public health strategies implemented in Uttar Pradesh—with little WHO backing or support—public health agencies and organizations in this Northern Indian state employed thousands of healthcare workers to visit tens of thousands of towns and villages, armed with SARS-CoV-2 tests, isolation and quarantine protocols, care coordination support, and home medicine kits which included ivermectin.


    In a press release, WHO announced Uttar Pradesh’s success taking on Delta, yet completely suppressed the fact that ivermectin was in those home medicine kits.


    The regional approach deviated from the WHO narrative of universal vaccination first, yet WHO also needed to tap into and leverage those regional public health mechanisms to achieve its aim of 70% vaccination. But that didn’t necessitate ignoring data and unfolding science. A shameless act promoted by self-interest; bureaucrats showed they were more interested in their own mission than the true health of poor people around the world.


    Other LMICs that embraced ivermectin were quickly lectured or worse, by WHO, who has the power to withhold much-needed funding in these poor countries. Individuals associated with three governments confided in TrialSite that very fact.


    The use of ivermectin in India showed so much benefit that the drug was placed on the national guidance list, much to the frustration of WHO and other international groups, not to mention industry, for a period, but continuous pressure and the waning of the Delta variant led to the removal of the national guidance.


    WHO’s disrespectful dismissal of Uttar Pradesh’s inclusion of ivermectin made healthcare activists furious—so much so that a group of Indian lawyers sued WHO and its chief scientist as a result.


    Because Uttar Pradesh’s approach to combating the Delta variant of SARS-CoV-2 deviated, in the minds and plans of WHO bureaucrats, from that rigid, top-down central planning approach of the agency: consequently, the agency employed nasty medical and scientific communications protocols to attack, even vilify a drug celebrated for its achievements, including a Nobel Prize in the war against parasitic disease in the tropical world.


    Omicron Intensifies Urgency

    WHO reminds all on its website that the emergence of the highly infectious Omicron variant represented yet another urgent reminder for the need to vaccinate 70% of the population. Ultimately, IAVG’s mission, again an arm of WHO to drive equity, now addresses the failure to achieve its goals during the pandemic, highlighted in a document labeled “The Strategy to Achieve Global COVID-19 Vaccination by Mid-2022.”


    A noble goal yet highly ambitious goal for one organization, WHO seeks to “minimize deaths, severe disease, and overall disease burden; curtail the health system impact; fully resume socio-economic activity, and reduce the risk of new variants.”


    WHO’s strategy document highlights “high population immunity is essential” for achieving the goals which equal broad-based vaccination. But why 70%? What is it about that number that matters?


    According to WHO’s latest strategy document, the organization’s goal of achieving the 70% target is “based on current knowledge:” that is that 70% of every target nation must be immunized starting with A) high-risk populations, B) adult population, then C) adolescent population.


    Question WHO

    Underlying WHO’s entire approach remains several serious assumptions that should be thoroughly vetted by external independent and unbiased experts. That vaccines do not wane in effectiveness—e.g., that these still immature products are not associated with durability issues fundamentally underlies many of WHO’s assumptions for its 70% target.


    WHO assumes that after 70% of those populations deemed high risk (elderly, comorbidities, etc.), as well as all adults and adolescents, are immunized, this leads to a reduction in transmissibility of the disease. But is this true? The data implies not over time, assuming continuous mutations.


    However, this primary assumption remains highly questionable based on unfolding data and science. Even Bill Gates, the financier of many of the public worldwide vaccination programs, went on the record recently acknowledging that the COVID-19 vaccines don’t stop transmissibility but rather help stop more severe disease and death. Yet again much of the population of sub-Saharan Africa may not fall in the high-risk categories for COVID-19 (e.g., young population, not obese, etc.).


    This, however, doesn’t stop WHO and its various groups and committees such as IAVG in its aggressive mission for worldwide immunization. Target totals include:


    Dates Targets

    End of Sept 2021 10% coverage all nations

    End of Dec 2021 40% coverage all nations

    End of June 2022 70% coverage all nations


    The price tag for this scheme? $55 billion based on a confluence of factors and inputs, including an average cost of COVID-19 vaccine per dose at $10. WHO declared in their strategy document that, “A majority of the vaccine doses needed by these countries has been secured by the significant financing invested through COVAT, AVAT, and bilateral contracts.”


    Yet, WHO still needs money. What for? According to the organization’s plans, they have economic urgency totaling a call for $8 billion (U.S.) associated with the mobilization and application of additional domestic, grant, and concessional financing to close the remaining funding gap for in-country program delivery of these doses. The entire strategy can be reviewed here.

    https://cdn.who.int/media/docs/default-source/immunization/covid-19/strategy-to-achieve-global-covid-19-vaccination-by-mid-2022.pdf


    Conclusion

    WHO has all but acknowledged that their goal of 70% vaccination of the poorest countries’ populations has fallen short while expressing in their recent strategy document the urgent need for an additional $8 billion from the U.S. to achieve their global goals.


    Key points to consider when considering the current WHO COVID-19 strategy:


    Not all nations and populations within nations face the same risk for severe COVID-19, yet they are treated as one-size-fits all

    The COVID-19 vaccines, at least the current batch of product, wane in effectiveness—hence, the boosting in the developed nations which could continue onward

    Plenty of study results advance the known science of the existing COVID-19 vaccines—with variants such as Delta and Omicron, after just several weeks transmissibility is not just probable but likely among the fully vaccinated given rapidly growing rates of breakthrough infections

    As related to above, what if continuous variants emerge requiring continuous boosts—is this a sustainable model—financially and economically as well as from a health perspective

    WHO doesn’t mention that the production and distribution not to mention specialized refrigeration needs of the mRNA-based vaccines cannot be easily reproduced in much of the LMICs

    90%+ of all SARS cases are mild to asymptomatic—hence, early treatment may likely represent a superior care model, especially in LMICs with not only emergence of pharmaceutical antivirals but also numerous possible repurposed treatments (fluvoxamine, ivermectin, famotidine, and many more investigational approaches covered by TrialSite)

    A top-down, bureaucratic, centralized planning approach to combating this pandemic is superior to decentralized health models—TrialSite seriously questions this model, particularly after two years of experience with the pandemic

    The model above assumes ever more billions of dollars to fuel an expensive, top-down model which in many ways is comparable to China’s approach—the latter is the world’s second largest economy with large export-led financial surplus—but even China, TrialSite reports, strains under a combination of Zero Tolerance and mass vaccination with subpar products

    Assumes no regulatory or agency capture by industry or financiers

    Many more assumptions could be included above.


    How well have national health authorities combined with international groups such as WHO done combating this pandemic given the hundreds of billions of dollars spent in just over two years?


    While the vaccines are touted, actually revered as amazing feats—and Big Pharma and biotech are capable of amazing efforts–just how amazing is a vaccine that requires four or even five boosts in just one year to 15 months?


    It’s time to take a step back and assess WHO and other pandemic fighting assumptions with a more objective, unbiased, and rational lens

  • WHO’s COVAX was established to ensure an equitable COVID-19 vaccine distribution model. TrialSite reported late in 2021 that the model to vaccinate the poorest countries failed miserably despite tens of billions allocated to COVAX via WHO and GAVI, along with participation by some vaccine producers.

    Great to see that the world wide vaccine terror organization did fail to distribute Pfizer crap to the poorest. Most of them got an Ivermectin treatment and now belong to the long time protected group where as the vaccine terror victims (Pfizer/Oxford) live on very shaky ground and certainly will face stronger ADE with each future virus as already seen with Delta and Omicron.


    In the near future the vaccine terror victims will have to isolate ^^ to avoid the spreading of new corona virus...

  • Fact Check: The Daily Sceptic’s Take on Triple-Vaccination and Omicron


    Fact Check: The Daily Sceptic’s Take on Triple-Vaccination and Omicron
    A Daily Sceptic report about preliminary analysis from the UK’s Office for National Statistics (ONS) in December has gone viral. The ONS
    trialsitenews.com


    A Daily Sceptic report about preliminary analysis from the UK’s Office for National Statistics (ONS) in December has gone viral. The ONS revealed that people who have triple vaccinations are more likely to be infected with the Omicron variant compared to the other variants. Other data also shows that Omicron is more transmissible compared to other variants and it is more likely to evade the immune response.


    The Office for National Statistics (ONS) looked at the data from the COVID-19 Infection Survey from November 29 to December 12, 2021. Of 1,816 individuals testing positive with COVID-19, 115 had the Omicron variant. ONS compared the characteristics of people with Omicron and Delta variants, focusing on those with strong positive results, as weaker test results are less reliable at distinguishing between variants.


    Based on a two-week period, this early analysis identified seven characteristics associated with Omicron infection, one of which was vaccination status. Compared to the unvaccinated, people who had three shots of vaccine were more likely to have the Omicron variant.


    The Daily Sceptic explained that the data does not prove vaccines are to blame for increased Omicron cases among the vaccinated, but only that a vaccinated person is more likely to be infected with Omicron rather than other variants. The data suggest this is especially true for those who have received three doses of vaccine. The study does not address the effectiveness of vaccines for reducing hospitalization and death from Omicron. The study concluded that Omicron evades vaccines’ protection.


    Global studies and reporting on Omicron compared

    Reuters published a fact check on the ONS data and also concluded that Omicron has significant vaccine evading ability but said the findings have driven misleading social media posts that suggest that vaccines increase susceptibility to COVID-19. Jonathan Cook, communication officer at ONS, told Reuters that, regardless of the variant, the unvaccinated are more susceptible to infection.


    Reuters cited a study from Imperial College London which shows that Omicron can evade immunity gained both from the two-shot vaccines and natural infection.


    Nature also reported that studies from Sweden, Germany, South Africa, and Pfizer-BioNTech suggest that compared to other COVID variants, Omicron extensively blunts the potency of neutralizing antibodies, modifying vaccine effectiveness.


    Booster Shot vs. Omicron

    Various studies, including those from the UK Health Security Agency and University of Oxford, have shown that COVID-19 vaccine effectiveness against Omicron drops after 5-6 months. However, there is evidence that a booster shot increases it again.


    A preprint study from Statens Serum Institut showed that vaccine effectiveness against Omicron among recently vaccinated individuals was 55% for Pfizer vaccine and 37% for Moderna vaccine. Both vaccines’ effectiveness dropped rapidly over five months, but after the booster shot effectiveness increased to 55%. A study from Israel also showed that booster shot creates protection against the Omicron variant.


    A study accepted to be published in Nature from Columbia University and the University of Hong Kong showed that Omicron resists antibodies gained from four prominent vaccines, Pfizer, Moderna, Johnson, and AstraZeneca. Even with a booster shot with an mRNA vaccine, the body shows diminished neutralizing defense against Omicron.


    Speaking on behalf of BioNTech on December 8,2021, CEO Ugur Sahin said “we expect significant protection against any type of COVID-19 mediated by Omicron in individuals who have received the third vaccine.” By December 20, 2021, the story changed as Sahin warned that three shots of vaccine won’t be enough to protect against Omicron. “It is obvious we are far from 95% effectiveness that we obtained against the initial virus,” he said. The company is developing a new vaccine based on Omicron spike proteins and their 32 mutations, which they hope ready by March 2022.


    Triple-Vaccinated More Than FOUR Times As Likely to Test Positive For Omicron Than Unvaccinated, Data Shows – The Daily Sceptic
    According to new ONS data, the triple-vaccinated are 4.5 times more likely to test positive for Omicron than the unvaccinated. The double-vaccinated,…
    dailysceptic.org

  • Austria Will Mandate COVID Vaccinations and Impose Fines. The Rest of Europe May Follow


    Austria Will Mandate COVID Vaccinations and Impose Fines. The Rest of Europe May Follow
    Austria is set to become the first European country to make vaccines mandatory. Starting in February any citizen of Austria, 18 or over, who is
    trialsitenews.com


    Austria is set to become the first European country to make vaccines mandatory. Starting in February any citizen of Austria, 18 or over, who is unvaccinated against COVID-19 will be fined up 3,600 euros for violating the law.


    The new rule was first proposed in December and has been subject to intense debate. Chancellor Karl Nehammer has acknowledged the mandate is a sensitive topic that has divided his countrymen. About 75 percent of Austrians have been vaccinated which is below the average of European Union countries. Nehammer has warned that restrictions will be tightened by mid-March against those resisting vaccination.


    Pregnant women and those with medical exemption claims may be excused from the mandate, according to Austrian authorities.


    “Without obligatory vaccination, we will always lag behind,” Austrian health minister Wolfgang Mueckstein said. He added the current Omicron variant will not be the last and it is still unclear whether immunity gained after infection will persist or compare to vaccine-inducted immunity. Austria has seen a record rise in new COVID cases in the past week. The country has recorded nearly 14,000 COVID deaths and over 1.4 million cases of the disease. Austria has a population of about 9 million.



    On December 15, thousands protested the new mandates on the streets of Vienna, following on weeks of mandate protests across Europe. Greece and Italy have already imposed vaccine mandates for “older” people with Greece beginning to fine unvaccinated people over 60 around 115 dollars a month.


    Austria’s new restrictions may spark more street demonstrations.


    Israel is the world leader in multi-dose vaccinations – an estimated 97 percent of the population has been vaccinated but the nation continues to experience high COVID infection and hospitalization rates. Ehud Qimron, a top Israeli immunologist called on the Israeli Ministry of Health to admit that mass vaccination has been a “failure”. Over the past week, Israel reported more than 48,000 cases and 27 deaths, which is a 92 percent increase over the previous week’s fatality count.


    Austria tweaks plans over being first in EU to make vaccines mandatory
    “Without obligatory vaccination, we will always lag behind,” said Austria's health minister Wolfgang Mueckstein.
    www.euronews.com

  • Respiratory viruses that hijack immune mechanisms may have Achilles’ heel

    Respiratory viruses that hijack immune mechanisms may have Achilles’ heel
    One viral protein could provide information to deter pneumonia causing the body’s exaggerated inflammatory response to respiratory viruses, including the virus…
    www.eurekalert.org


    Human Respiratory Syncytial Virus NS2 Protein Induces Autophagy by Modulating Beclin1 Protein Stabilization and ISGylation


    Human Respiratory Syncytial Virus NS2 Protein Induces Autophagy by Modulating Beclin1 Protein Stabilization and ISGylation | mBio
    Understanding host-virus interactions is essential for the development of effective interventions against respiratory syncytial virus (RSV), a paramyxovirus…
    journals.asm.org


    ABSTRACT

    Paramyxoviruses such as respiratory syncytial virus (RSV) are the leading cause of pneumonia in infants, the elderly, and immunocompromised individuals. Understanding host-virus interactions is essential for the development of effective interventions. RSV induces autophagy to modulate the immune response. The viral factors and mechanisms underlying RSV-induced autophagy are unknown. Here, we identify the RSV nonstructural protein NS2 as the virus component mediating RSV-induced autophagy. We show that NS2 interacts and stabilizes the proautophagy mediator Beclin1 by preventing its degradation by the proteasome. NS2 further impairs interferon-stimulated gene 15 (ISG15)-mediated Beclin1 ISGylation and generates a pool of “hypo-ISGylated” active Beclin1 to engage in functional autophagy. Studies with NS2-deficient RSV revealed that NS2 contributes to RSV-mediated autophagy during infection. The present study is the first report to show direct activation of autophagy by a paramyxovirus nonstructural protein. We also report a new viral mechanism for autophagy induction wherein the viral protein NS2 promotes hypo-ISGylation of Beclin1 to ensure availability of active Beclin1 to engage in the autophagy process.

    IMPORTANCE Understanding host-virus interactions is essential for the development of effective interventions against respiratory syncytial virus (RSV), a paramyxovirus that is a leading cause of viral pneumonia in infants. RSV induces autophagy following infection, although the viral factors involved in this mechanism are unknown. Here, we identify the RSV nonstructural protein 2 (NS2) as the virus component involved in autophagy induction. NS2 promotes autophagy by interaction with and stabilization of the proautophagy mediator Beclin1 and by impairing its ISGylation to overcome autophagy inhibition. To the best of our knowledge, this is the first report of a viral protein regulating the autophagy pathway by modulating ISGylation of autophagy mediators. Our studies highlight a direct role of a paramyxovirus nonstructural protein in activating autophagy by interacting with the autophagy mediator Beclin1. NS2-mediated regulation of the autophagy and ISGylation processes is a novel function of viral nonstructural proteins to control the host response against RSV.


    DISCUSSION

    Previous studies have shown that respiratory syncytial virus (RSV) promotes autophagy in mice and in cells to modulate the innate immune and antiviral responses during infection (10, 12, 13). Autophagy also regulates RSV-associated lung pathology and pulmonary disease in infected mice (10, 12). Although autophagy plays a multifunctional role during RSV infection, the viral factor(s) that mediates such proautophagy activity remained unknown. Here, our studies identified the nonstructural protein NS2 as a viral proautophagic factor that drives RSV-induced autophagy. Our study uncovered a dual proautophagy role of RSV NS2 protein: (i) NS2 interaction with the proautophagy mediator Beclin1 results in Beclin1 stabilization, and (ii) NS2 impairs the antiautophagic effect of ISGylation on Beclin1. These two mechanisms ensure abundant availability of active Beclin1 to engage in autophagy.

    Using immunoblot assays to survey the autophagy flux markers LC3II and p62, we found that RSV induces the formation and maturation of functional autophagic compartments. RSV-induced autophagy was characterized by early stabilization of the proautophagy mediator Beclin1, followed by LC3II formation and p62 reduction (Fig. 6). Additionally, the RSV protein NS2 contributed to RSV-induced autophagy, as NS2-deficient virus failed to stimulate autophagic flux or promote Beclin1 protein stabilization (Fig. 6). Coimmunoprecipitation and coimmunofluorescence assays showed that NS2 interacts and colocalizes with Beclin1 (Fig. 2), and this interaction is central to set the autophagy pathway in motion. NS2-Beclin1 binding stabilizes Beclin1, impeding its degradation by the cellular machinery (Fig. 5). Beclin1 protein levels are elevated due to NS2-mediated stabilization (Fig. 5), increasing the amount of Beclin1 available to form VPS34-VPS15-Beclin1-ATG14/UVRAG class III phosphatidylinositol 3-kinase (PI3K) complexes during autophagy initiation and maturation. Expression of NS2 protein augmented the autophagy marker LC3II and its incorporation into maturing autophagosomes as LC3II puncta, indicating a link between Beclin1 enrichment and autophagy activation (Fig. 1).

    Beclin1 is subject to activating and deactivating posttranslational modifications that regulate its ability to interact with other PI3K complex proteins (reviewed in reference 38). Beclin1 ISGylation occurs due to conjugation of interferon-stimulated gene 15 (ISG15) to Beclin1 domains BH3 and CCD (6). ISGylation of Beclin1 in domains BH3 and CCD (6) inhibits autophagy by competing with Lys63 polylinked ubiquitination, which is essential for autophagy activation (6). RSV infection induces ISGylation (37) and upregulation of ISG15 mRNA in lung epithelial cells (39), while ISG15 mRNA is also upregulated in clinical samples from pediatric RSV patients (37). Surprisingly, our studies show that the NS2-Beclin1 interaction hampers Beclin1 ISGylation (Fig. 7), creating a pool of “hypo-ISGylated” Beclin1 to engage in active autophagy. To date, there have been no reports of viral proteins controlling ISGylation to regulate autophagy. We report a novel mechanism of virus-mediated autophagy induction in which a viral protein (i.e., RSV NS2 protein) promotes hypo-ISGylation of Beclin1 and hence its activation for the autophagic response.

    Other RSV-related paramyxoviruses have evolved different strategies to manipulate the autophagy pathway by using viral proteins. The paramyxovirus measles virus (MeV) induces successive waves of sustained autophagy flux by three independent mechanisms (40, 41). One of the MeV autophagy-inducing mechanisms involves the nonstructural C protein, although the exact molecular basis remains undefined and a direct involvement of C protein in autophagy induction has yet to be established. Morbilliviruses also require interaction of the viral glycoproteins F and H with cell receptors and cell membrane fusion (i.e., syncytium formation) to induce autophagy and facilitate cell-to-cell spread (42). The NP and P proteins of Newcastle disease virus (NDV) induce autophagy through an endoplasmic reticulum (ER) stress-related unfolded protein response (PERK and ATF6 pathways) (43). In contrast, the paramyxovirus human parainfluenza virus type 3 (HPIV3) induces incomplete autophagy by blocking autophagosome-lysosome fusion via its P (phosphoprotein) protein (44). Our study revealed a viral protein (i.e., RSV NS2) interacting with Beclin1 protein to modulate its stability and activation for a productive autophagic response. To the best of our knowledge, our current study is the first report of a paramyxovirus nonstructural protein directly activating autophagy by modulating Beclin1. Furthermore, NS2 manipulation of both the autophagy and ISGylation pathways is a novel function that expands its ability to control the host response against RSV.

    We propose a model of the molecular mechanism underlying RSV-induced autophagy (Fig. 8). We demonstrate that the RSV nonstructural protein NS2 interacts with and stabilizes the proautophagy regulator Beclin1. The NS2-Beclin1 interaction increases Beclin1 protein levels and makes it available for autophagy by disrupting Beclin1 protein ISGylation. Autophagy likely has multifold effects in the pathobiology of RSV by regulating lung inflammation and airway disease severity (13, 45). It may also have an immune-modulatory effect in the airway by controlling the adaptive immune response in the RSV-infected respiratory tract (13, 45). Furthermore, it remains unknown whether other redundant proautophagy mechanisms take place during RSV infection or how RSV proteins escape autophagy-dependent degradation. Understanding the mechanisms governing the ability of RSV to manipulate the immune response is valuable for the development of therapeutic and prophylactic interventions targeting the host. This is of paramount importance to control viruses that insidiously hijack and deregulate innate immune antiviral responses to facilitate virus propagation.

  • Based on a two-week period, this early analysis identified seven characteristics associated with Omicron infection, one of which was vaccination status. Compared to the unvaccinated, people who had three shots of vaccine were more likely to have the Omicron variant.

    This is obvious from actual Israel data too. The rate for severe illness among boostered is much higher...The gap actually is widening. Happy ADE days....

  • The omicron rate in Switzerland was 87% about 10 days ago. This means that we still have quite a high absolute number of delta cases in the range of about 5000/day. These must be set in relation to hospital data.

    Of course we also know that the hospital data is fudged with non CoV-19 admitted counted as positive.


    In UK data is even worse as > 93% must be counted as recovered. So all data about vaccine protection simply is useless.

    May be in reality we already see that vaccine only protected die much more often than unvaccinated. At least for Omicron this is already the case in Israel.


    So please stay off Pifzer/Oxford-Zeneca crap boosters. J&J has be claimed to work as it also did work best for Beta. Moderna has a second RNA that still a kind of helps.

  • This is obvious from actual Israel data too. The rate for severe illness among boostered is much higher...The gap actually is widening. Happy ADE days....

    Fourth COVID vaccine still doesn’t stop Omicron, new Israeli study shows

    Fourth COVID vaccine still doesn’t stop Omicron, new Israeli study shows
    The study raised questions about Israel’s decision to be the first in the world to offer a second booster shot — and fourth overall — to its over-60 population.
    nypost.com


    Even a fourth shot of a COVID-19 vaccine is “not good enough” to prevent Omicron, according to a preliminary study in Israel.


    Sheba Hospital last month tested a fourth shot given to more than 270 medical workers, with 154 getting the Pfizer jab and 120 receiving Moderna.


    The researchers revealed Monday that both groups showed a “slightly higher” increase in antibodies than after the third shot — but still not enough to prevent Omicron, the latest variant responsible for the vast majority of infections around the world.


    “Despite increased antibody levels, the fourth vaccine only offers a partial defense against the virus,” said Dr. Gili Regev-Yochay, director of the hospital’s infection disease unit leading the study.


    The study saw “many infected with Omicron who received the fourth dose,” she said. “Granted, a bit less than in the control group, but still a lot of infections.”

    The vaccines, which were more effective against previous variants, offer less protection versus Omicron,” Regev-Yochay said, adding that the vaccines are “not good enough” to prevent the less-severe new variant.


    The findings have not yet been published and do not reveal specific data.

    But the study raised questions about Israel’s decision to be the first in the world to offer a second booster shot — and fourth overall — to its over-60 population.


    The government says over 500,000 people have received the second booster in recent weeks. But the country has still seen record-high infections recently, even though 80 percent of Israel’s adult residents have received two shots and more than half have gotten boosted.

    Hours after releasing the results, Sheba Hospital called for “continuing the vaccination drive … even though the vaccine doesn’t provide optimal protection against getting infected with the variant.”


    Hebrew media reported that the hospital was pressured into issuing that statement after the Health Ministry didn’t like the study’s results, according to The Times of Israel.

  • Not sure if the conclusion from TSN and/or DailySceptic was correct in the end. Here is some pro & con to get a better picture...


    One of the commenters of this report:


    "4.5 times more likely to have Omicron than any other variant. NOT 4.5 times more likely to have COVID than the unvaccinated. This shows Omicron's ability to evade neutralizing antibodies produced by vaccines. It doesn't show that the vaccinated are at a higher risk.)...


  • Missoula doctor boasts new, cheap, and effective COVID-19 treatment


    https://nbcmontana.com/newslet…UlKY1FZaDBYLW8yMVZtX01PQw..



    In an off-label clinical trial, Peschel used this cocktail on six patients who tested positive for COVID-19 and measured their stats. None of the patients was admitted to the hospital, they all experienced few to no symptoms, and their immune response and oxygen levels stayed at normal levels.


    “Let's give the high-risk patients the Peschel Protocol. They get their symptoms, get their diagnosis, and we start treatment as soon as possible,” said Peschel. “Treat them daily with these four drugs for the course of the illness, we measure the CRP, the oxygen sats, we graph it out, and we have almost normalized the most aggressive immune response to near normal. We’ve eliminated all the end point of hospitalization and death in both high-risk and low-risk patients, 100%,” said Peschel.


    Peschel has been working to obtain FDA approval; however, he says the process is difficult. He has been gaining more momentum locally, and Missoula Mayor John Engen voiced his support for the treatment.


    “FDA is a hard bureaucracy to crack. As Dr. Peschel will tell you, there's not much money to be made here, and that's part of the problem,” said Engen.


    Engen plans to help back Peschel in any way he can.


    “I've long been in support of Walt getting a chance to test this in a really meaningful way. What I know is that the folks who have volunteered to use the Peschel Protocol have seen chronic disease arrested,” said Engen.


    One of Peschel’s higher risk patients, Phil Currie, was put on the Peschel Protocol when he first tested positive for the virus. He says he had few symptoms and fully recovered.


    “I had a little bit of a stuffy nose, but that's all, and for somebody who's at high risk, I'm 80 years old,” said Currie.


    Right now, Peschel is prepared to expand his trial to more patients. He is willing to work with current providers and stresses that this is a safe treatment option.


    “I would recommend that we find out if the protocol reduces these endpoints adequately. I would then manufacture as much of this medicine as I could and use it to control the present pandemic” said Peschel.


    Those interested in learning more about the COVID-19 treatment are encouraged to call Peschel at his number directly: 406-880-3343

  • Isn't there any kind of statistics on blood level antibodies (?) or other data that somehow support this high infection rate in UK?

    The UK vaccine report say 98,7% have S (Spike) antibodies...But the unlucky vaccinated got tons of useless antibodies for omicron than fit up to 1000x less than needed...

    We here have a PCR positive rate of close to 40% what indicates that at least 10x more cases are running undetected. UK tests more so there are less undetected cases. We know the ratios from full area testing.


    The only advise I can give do not use Pfitzer boosters. The stock exchange currently means the same...

    Yahooist Teil der Yahoo Markenfamilie

  • We here have a PCR positive rate of close to 40% what indicates that at least 10x more cases are running undetected.

    Factor more than10?

    An actual source estimates ca. 4x… (Paywall unfortunately, so I don’t know the exact content…)


    «Nur» 30'000 Infektionen pro Tag - sind es in Wahrheit 120'000?
    Die Taskforce unterschätzte im Dezember das Tempo der Omikron-Ansteckungen. Viel früher als vorausgesagt, nämlich schon Anfang Januar, sprangen die Fallzahlen…
    www.aargauerzeitung.ch

  • An actual source estimates ca. 4x

    I once linked the data of the area test done in URI (CH) and the resulting change in positive rate. So with a positive rate of 7.5% you miss 1/2 of all cases. So with a positive rate of 14% you just get 1/4 of the cases thus now with about 39% you get less than 1/10 of the cases.

    Historically I has been known that above 5% positive rate you miss an unknown number of cases.


    So currently in Switzerland must be about 400'000 active Omicron cases with most of them without symptoms. Fact is nobody wants a test as this means quarantine.

    400'000 active cases means effectively 160'000...200'000 daily new cases as the turnover rate is 4..5 days (Omicron only, not for delta that is still here) .

    The above mentioned factor 4 certainly is wrong but whether it is 8,10,12 is just guessing.


    Everybody can get Omicron even the recovered ones but for them it's just a soft cold.


    The real Omicron victims will be the vulnerable that missed an infection so far. But be aware also the brave old classic corona virus can kill! Thus do your prevention - especially the ones with vaccination only!

Subscribe to our newsletter

It's sent once a month, you can unsubscribe at anytime!

View archive of previous newsletters

* indicates required

Your email address will be used to send you email newsletters only. See our Privacy Policy for more information.

Our Partners

Supporting researchers for over 20 years
Want to Advertise or Sponsor LENR Forum?
CLICK HERE to contact us.