The Playground

    Quote from ZenoOfElea

    Not sure if this has been linked to before.

    Data from European Centre for Disease Prevention and Control on vaccine effectiveness.

    Thanks for the link! The data clearly shows that we face large differences among different countries. In general vaccines protect for about 50% (Death) at best, what agrees with most data sources also for UK contrary to the state official claims! Countries that claim a higher protection rate often have a very high protection from recovered people.


    If we look at absolute numbers then one thing is clear. 97% of all deaths happen among age > 70! In this age class we see always about 50% protection.

    Why do we see much a higher numbers of prevented deaths in this report? Simply because of illegal data mixing. Age 60..70 only makes a tiny contribution to the overall deaths and thus mimics a high protection that in reality is not there. Also far more people live in the age group 60..70 thane.g 80+!


    This report is a good example how the cheaters dominate the CoV-19 fake news scenery.


    direct link:: https://www.eurosurveillance.o…B70EFE28D9003A2588B69BC65

    COVID-19 Breakthrough: Scientists Discover How the SARS-CoV-2 Virus Evades Our Immune System


    SARS-CoV-2 inhibits induction of the MHC class I pathway by targeting the STAT1-IRF1-NLRC5 axis


    SARS-CoV-2 inhibits induction of the MHC class I pathway by targeting the STAT1-IRF1-NLRC5 axis - Nature Communications
    The presentation of viral antigens to T cells via the MHC molecules is a critical component of the host response to viral infection. Here the authors suggest…
    www.nature.com


    Abstract

    The MHC class I-mediated antigen presentation pathway plays a critical role in antiviral immunity. Here we show that the MHC class I pathway is targeted by SARS-CoV-2. Analysis of the gene expression profile from COVID-19 patients as well as SARS-CoV-2 infected epithelial cell lines reveals that the induction of the MHC class I pathway is inhibited by SARS-CoV-2 infection. We show that NLRC5, an MHC class I transactivator, is suppressed both transcriptionally and functionally by the SARS-CoV-2 ORF6 protein, providing a mechanistic link. SARS-CoV-2 ORF6 hampers type II interferon-mediated STAT1 signaling, resulting in diminished upregulation of NLRC5 and IRF1 gene expression. Moreover, SARS-CoV-2 ORF6 inhibits NLRC5 function via blocking karyopherin complex-dependent nuclear import of NLRC5. Collectively, our study uncovers an immune evasion mechanism of SARS-CoV-2 that targets the function of key MHC class I transcriptional regulators, STAT1-IRF1-NLRC5.


    Discussion

    In this study, we showed that the induction of MHC class I gene expression is impaired by SARS-CoV-2 infection. Gene expression studies in the lung and airway epithelial cells of COVID-19 patients as well as SARS-CoV-2 infected epithelial cell lines showed that SARS-CoV-2 inhibits the upregulation of MHC class I in epithelial cells during virus infection. Since MHC class I is critical for antiviral immunity, the MHC class I pathway has been known as a favorable target for immune evasion by various viral strains. Our data indicate that impaired upregulation of the MHC class I gene expression in the airway and intestinal epithelial cells during SARS-CoV-2 infection interferes with the CD8 T cell-dependent cellular immunity, thus causing a higher risk of exacerbation of viral loads and prolonged infection4,5,6,50,51.


    Intriguingly, SARS-CoV-2 targets NLRC5 at both transcriptional and functional levels to escape from the MHC class I pathway. Since NLRC5 orchestrates the concerted expression of the major components involved in the MHC class I pathway, it has been postulated that NLRC5 would be an attractive target for immune evasion52,53,54. Considering that inhibition of NLRC5 alone can lead to suppression of the MHC class I pathway, it is reasonable to speculate that targeting NLRC5 would be much more efficient than suppressing each component of the MHC class I pathway. In fact, in the case of cancer, in which MHC class I also plays crucial roles, NLRC5 was found to be the most critical host factor targeted by cancer cells to evade anti-cancer immunity. For example, epigenetic or genetic alterations such as promoter methylation, genetic mutations, or copy number loss of NLRC5 gene can cause impaired expression or function of NLRC5, associated with reduced MHC class I expression, impaired CD8 cell recruitment, and poor survival of cancer patients52. In this regard, it is reasonable to hypothesize that the expression level of NLRC5 in COVID-19 patients might be associated with the disease severity and mortality. It would be interesting to see if the genetic variability in the expression of NLRC5 and other MHC class I-related molecules are associated with the pathogenesis of SARS-CoV-2 and other viral infectious agents. Further study is required to address this speculation.


    NLRC5-dependent MHC class I gene expression is induced by both type I, and more potently type II interferon10,11. It appears that SARS-CoV-2 can inhibit both signaling pathways. As shown previously and also confirmed in this study, the type I interferon signaling pathway is inhibited by SARS-CoV-2. Besides, STAT1 activation can be inhibited even in the presence of IFNγ, the most potent inducer of STAT1 activation, indicating that SARS-CoV-2 strongly suppresses the type II IFN signaling pathway. As NLRC5 induction is STAT1-dependent, impaired STAT1 function directly leads to transcriptional suppression of the MHC class I genes. In addition to NLRC5, the induction of IRF1, another co-transcription factor involved in the MHC class I activation, is suppressed because IRF1 expression is also STAT1-dependent.


    In addition to transcriptional suppression of NLRC5 expression, we found direct inhibition of NLRC5 function by a SARS-CoV-2 protein (Fig. 5). Screening of inhibitory molecules of SARS-CoV-2 showed that SARS-CoV-2 ORF6 inhibits NLRC5 CITA function. Cellular localization studies indicate that this is likely to be achieved by the inhibition of nuclear translocation of NLRC5. Likewise, we found that SARS-CoV-2 ORF6 also inhibits IRF1 function by blocking the IRF1 nuclear import. Inhibition of nuclear translocation of NLRC5 and IRF1 is reminiscent of the recent findings of the inhibitory nature of ORF6 of SARS-CoV and SARS-CoV-2 in innate immunity.


    Recently it was shown that ORF6 could block the nuclear translocation of several transcription factors such as STAT1 and IRF3 by inhibiting karyopherin-mediated nuclear import, thereby suppressing immune responses32,33.


    Although all three transcription factors, STAT1, IRF1, and NLRC5, commonly utilize the karyopherin complex for nuclear translocation, their partner karyopherin alpha subunits are different. Nevertheless, SARS-CoV-2 ORF6 can simultaneously block the nuclear import of all three factors, suggesting that SARS-CoV-2 ORF6 may exert its inhibitory role by targeting the downstream events of the karyopherin-mediated nuclear import. In fact, during our preparation for the manuscript, one study has demonstrated that SARS-CoV-2 ORF6 directly binds to Nup98, a component of the nuclear pore complex, and prevents the karyopherin-cargo complex-mediated nuclear transportation49. In agreement with this study, we found that SARS-CoV-2 ORF6 suppressed the nuclear localization of all karyopherin alpha subunits that are responsible for nuclear import of STAT1, IRF1, and NLRC5 regardless of upstream molecule interaction (Fig. 6f).


    In this regard, it should be noted that although SARS-CoV ORF6 and SARS-CoV-2 ORF6 have a similar inhibitory effect, the mechanistic nature of their inhibitory function seems to be different. As mentioned above, whereas SARS-CoV-2 ORF6 blocks the nuclear import of multiple KPNA subunits (Fig. 6f), SARS-CoV ORF6 only selectively inhibits the nuclear import of KPNA2 via direct interaction44. It was shown that while SARS-CoV-2 ORF6 strongly interacts with Nup9849, SARS-CoV ORF6 showed a marginal association55. Instead, SARS-CoV ORF6-KPNA2 complex competes with other KPNA subunits to hijack KPNB1 from the target cargo molecule44. This mechanistic difference between SARS-CoV ORF6 and SARS-CoV-2 ORF6 could explain why MHC class I activation can be efficiently suppressed by SARS-CoV-2 but not by SARS-CoV23. We and others showed that the C' terminus region of ORF6 is critical for its inhibitory function (Fig. 7a–d). Notably, the amino acid sequence of C' terminus regions between SARS-CoV ORF6 and SARS-CoV-2 ORF6 is slightly different. Whether or not the mechanistic differences between these two ORF6s are due to the difference in amino acid sequence at their C' terminus tail still needs to be clarified.


    It should be noted that while ORF6 displays a strong inhibitory effect on the upregulation of MHC class I under the stimulated conditions such as IFNγ treatment, it does not seem to have much impact on the expression of the MHC class I under the steady state condition (Supplementary Fig. 10). Thus, the inhibitory effect of ORF6 alone cannot explain how the MHC class I gene expression was downregulated in the SARS-CoV-2-infected patient samples (Fig. 1a–c). In this regard, multiple mechanism, presumably, including other SARS-CoV-2 proteins, may be involved in the downregulation of the MHC class I expression during SARS-CoV-2 infection. Further study is required to address the more detailed function of ORF6 and other possible inhibitory mechanisms.


    Does SARS-CoV-2 ORF6 inhibit the nuclear import of all the nuclear-localized proteins? Since NLS-containing cargo proteins utilize karyopherin complex-mediated regulation for their nuclear translocation, SARS-CoV-2 ORF6 may broadly, but specifically, block the function of the NLS-containing proteins. Yet, there is a karyopherin-independent regulation of nuclear import via ankyrin domain-mediated mechanism. Interestingly, a recent study identified a molecular code termed RaDAR (RanGDP/AR) that regulates ankyrin repeat-mediated nuclear transportation56. Importantly, the authors further discovered that transcriptional regulators involved in pro-inflammatory responses, such as NF-κB or p53 pathways, generally utilize the RaDAR regulation pathway for nuclear import. Considering that whereas COVID-19 patients failed to produce type I and III IFNs, still pro-inflammatory cytokines are robustly generated. It would be interesting if this is due to the fact that SARS-CoV-2 does not affect the nuclear transport of those ankyrin repeat-containing transcriptional regulators. Further study is required to address this interesting question.


    Altogether, our study provides mechanistic insight into ORF6-mediated SARS-CoV-2 immune evasion via targeting the MHC class I antigen-presenting pathway (Fig. 7e). Moreover, our study indicates that SARS-CoV-2 possesses impressive immune evasion strategies targeting two critical host antiviral defense programs, the MHC class I and IFN signaling pathways, that result in successful viral adaptation to human hosts. The mechanistic findings in this study may provide potential molecular targets for developing the therapeutics against COVID-19.

    Quote from Fm1

    A week ago omicrm was coming to get us all, Fearmongering, then we find out it's more like a cold so what do the experts say now? Omicron has gone stealth, can't track it. Back to Fearmongering. They just can't help themselves


    Scientists find ‘stealth’ version of Omicron that may be harder to track

    https://amp.theguardian.com/wo…th-pcr-test-covid-variant

    FM1 - you will be better informed if you take facts not innuendo from these reports.


    This is just saying that current PCR tests - even the ones testing for S antigens that can pick up omicron (because spike has changed a lot) will not always pick up omicron rather than thinking it is delta.


    It is not surprising. It is not an attempt to frighten people, just a fact. Nor can I see why it should frighten people.


    You are seeing all these through a lens of what you think they are trying to do.


    Looking at UK data I can guarantee omicron is coming to get us all. I'm hoping that for those vaccinated it will be less harmful than delta. I certainly do not know that - we will find out in a few weeks. In the UK we will have mostly omicron infection (at a high rate) by Christmas.


    Regardless of how much you are right, thinking like that means you are processing conspiracy theories (right or wrong) at the expense of science.


    Personally, I'd rather stick to science.


    Except when it comes to pointing out Mark U's weird remarks about masks which seem borderline sociopathic (I don't think Mark U is sociopathic - just he has bought into an ideology that if followed up looks like that). This is the Playground, after all - such comments fair here.


    THH

    Thomas my friend, I've been right all along and I've backed it with the research. As for promoting conspiracy, I find it is you who uses character assignation as a weapon to promote your side. That in itself creates conspiracy. Follow me Thomas, I'll get you to the finish line healthy!

    Report: two doses of mRNA plus a booster are effective against omicron. See:


    Blood samples of people who received two Pfizer doses showed a 25-fold reduction in antibody levels against Omicron.
    www.nytimes.com


    QUOTE:


    Blood samples of people who received two Pfizer doses showed a 25-fold reduction in antibody levels against Omicron.


    Pfizer and BioNTech said Wednesday that laboratory tests suggest that three doses of their coronavirus vaccine offer significant protection against the fast-spreading Omicron variant of the virus.


    The companies said that tests of blood from individuals who received only two doses found more than a 25-fold reduction in antibody levels against the Omicron variant compared to an earlier version of the virus. That finding indicates that two doses alone “may not be sufficient to protect against infection” by the new variant, the companies said.


    But the blood samples obtained from people one month after they had received a booster shot showed neutralizing antibodies against the Omicron variant comparable to the levels of antibodies against a previous version of the virus after two doses, the companies said in a statement.


    At the same time, the tests suggested that the mutations in Omicron do not appear to significantly affect T cells — another critical part of the immune system’s response. That suggests “vaccinated individuals may still be protected against severe forms of the disease” after only two doses, the companies said. . . .

    Quote from Fm1

    Follow me Thomas, I'll get you to the finish line healthy!

    You never can convince a clown. For them cheating people just is fun...

    Quote from JedRothwell

    Pfizer and BioNTech said Wednesday that laboratory tests suggest that three doses of their coronavirus vaccine offer significant protection against the fast-spreading Omicron variant of the virus.

    This just is a Pfizer commercial...



    Serious reports tell that there is almost no protection from the Pfizer vaccine for Omicron. All early western Omicron cases have been detected among double vaxx.. as these get about 4x more often corona than unvaxx....


    Reality: https://www.buzzfeednews.com/a…micron-vaccine-antibodies


    What Pfizer looks at is just lab data not real world data. Pfizer has a well know cheating history by selecting from the 1% people with the highest S1 antibody count. So what Pfizer claims may work for the happy 1% with highest antibody count....(that vanishes after 3 months... hence a booster every three month..)


    I recommend Ivermectin after PCR+ and zinc 10..20mg/day ,V-D3 2000..5000 IU's a day + Quercetin as a preparation. This we recommend since > 18 months now.

    30% of Healthcare Professionals Across America Avoid Vaccination According to CDC Study


    30% of Healthcare Professionals Across America Avoid Vaccination According to CDC Study
    A report in the American Journal of Infection Control last month reports that a material number of healthcare professionals (HCP) around the United States
    trialsitenews.com


    A report in the American Journal of Infection Control last month reports that a material number of healthcare professionals (HCP) around the United States haven’t received their COVID-19 vaccine. After evaluating 3,3357,348 health care professional records across 2,086 hospitals the study authors conclude the rates of vaccination are far lower than anticipated. Led by authors from the Centers for Disease Control and Prevention (CDC) inquiring minds ponder why are so many HCP’s avoiding inoculation with the present COVID-19 vaccines?


    Led by CDC epidemiologist and corresponding author Hannah Reses, the study team poured through a trove of data reported to the U.S. Department of Health and Human Services Unified Hospital Data Surveillance System. What did they find?


    What follows is a table of vaccination rates by date:


    Date HCP COVID-19 Vaccination Rate

    January 2021 36.2%

    April 2021 60.2%

    August 25, 2021 66.7%

    September 15, 2021 70.0%

    Note the burst of vaccination during the start of the year when the vaccines became available. Dramatic growth in vaccination occurred between January 2021 and April 2021. But since then, despite an extraordinary push to get health professionals vaccinated—including an unprecedented mandate from the White House—the vaccination rate slowed markedly. What concerns drive the vaccine hesitancy of 30% of HCPs nationwide?


    Subscribe to the Trialsitenews "COVID-19" Channel

    No spam - we promise

    Email address

    Note varying vaccination rates by class of hospital. Major children’s hospitals often in major metropolitan areas count the highest rates of vaccination but even these still leave 23% unvaccinated. This is followed by short-term acute care hospitals, long-term acute care hospitals and critical access hospitals with the lowest vaccination rate. In these latter often rural health centers 36% of all health care professionals opted out, thus far, of the COVID-19 vaccination process.


    The study team reported that by COVID-19 vaccination ranged by type of medical center including the following:


    Hospital Category HCP COVID-19 Vaccination Rate

    Children’s hospitals 77%

    Short-term acute care Hospitals 70.1%

    Long-term acute care hospitals 68.8%

    Critical access hospitals 64.0%

    In a press release last month corresponding author Hannah Reses went on the record “Our analysis revealed that vaccine coverage among U.S. hospital-based HCP stalled significantly after initial uptake.” The government epidemiologist continued “Additional efforts are needed to improve HCP vaccine coverage and reduce the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission to patients and other hospital staff.”


    Conclusion

    The authors reported that about 30% of 3,3357,348 HCPs working in hospitals around America were not vaccinated at the time of publication. They declare “Additional efforts are needed to improve COVID-19 vaccine coverage among HCP, such as educational and promotional activities, communication efforts to address misinformation and providing paid time off to receive the vaccine.”


    The authors’ suspect that the new CMS rule promulgated by POTUS in September mandating vaccination among HCPs will lead to increased inoculations. Of course, a number of legal actions are challenging the various vaccine mandates.


    Lead Research/Investigator

    Hannah Reses, MPH Centers for Disease Control and Prevention

    Emma S. Jones, MS Centers for Disease Control and Prevention

    Donald B Richardson, PhD Johns Hopkins University

    Kristopher M. Cate, MS Johns Hopkins University

    David W. Walker, MPH Centers for Disease Control and Prevention

    Craig N. Shapiro, MD


    DEFINE_ME

    Studies suggest Pfizer shot may protect only partially against Omicron

    Studies suggest Pfizer shot may protect only partially against Omicron
    The Omicron variant can partially evade protection from two doses of Pfizer and partner BioNTech's COVID-19 vaccine, the research head of a laboratory at the…
    www.reuters.com


    Confusion rules !!!

    Quote from Fm1

    Thomas my friend, I've been right all along and I've backed it with the research. As for promoting conspiracy, I find it is you who uses character assignation as a weapon to promote your side. That in itself creates conspiracy. Follow me Thomas, I'll get you to the finish line healthy!

    I don't know who is right about a lot of this stuff...


    I have no idea whether you have been right all along, partly because I do not understand mots of what you have said, but I do know you sound arrogant and overconfident - I've always found that leads in the end to being wrong.


    Mainly what I object to is your sneering at the scientists when they are doing best effort work. It is easy for those not doing the work to poke holes.


    THH

    Quote from THHuxleynew

    And mocking scientists for being uncertain when any sane person would realise we cannot yet know is not helpful?


    THH

    Jesus Thomas, I was mocking jed not scientists, again trying to point the discussion to character assignation. And as for arrogant, if providing science that differs from your convictions is arrogant then yes I'm guilty and yes I'm right!

    Quote from Fm1

    Studies suggest Pfizer shot may protect only partially against Omicron

    This says:


    Dec 7 (Reuters) - The Omicron variant can partially evade protection from two doses of Pfizer (PFE.N) and partner BioNTech's COVID-19 vaccine, the research head of a laboratory at the Africa Health Research Institute in South Africa said on Tuesday.


    That is also what the New York Times said.

    Quote from Fm1

    Confusion rules !!!

    No. You are confused. Perhaps you did not read the reports carefully. The two sources agree. Two doses alone is less protective against omicron. Two doses plus a booster restore protection.


    Quote from Fm1

    Jesus Thomas, I was mocking jed not scientists,

    No, you are not mocking anyone. You made a careless mistake.


    Quote from Fm1

    And as for arrogant, if providing science that differs from your convictions is arrogant then yes I'm guilty and yes I'm right!

    No, you are wrong.

    Quote from stefan

    And then you vaccinate the old ones and at risk, is that not enough?

    No, that is not enough. Suppose an unvaccinated young person infects a 65-year-old with a breakthrough case. That 65-year-old is more likely to die than the unvaccinated 30 year old. By not vaccinating, young adults put the rest of society, including children and old people, at great risk. For no reason. Hundreds of thousands of people will die from breakthrough cases if young people do not get vaccinated.


    See:


    https://www.axios.com/age-coronavirus-risk-vaccines-2e1391b0-5d0e-4fa9-894b-4b894dc017c9.html

    Quote from stefan

    And then you vaccinate the old ones and at risk, is that not enough?

    It seems that the Director of the WHO agrees with you:


    WHO Speech


    "No country can simply vaccinate its way out of the pandemic.

    It’s not vaccines or, it’s vaccines and.

    And it’s not just about how many people are vaccinated, it’s about who is vaccinated.

    It makes no sense to give boosters to healthy adults, or to vaccinate children, when health workers, older people and other high-risk groups around the world are still waiting for their first dose. The exception, as we have said, is immunocompromised individuals.

    Countries with the highest vaccine coverage continue to stockpile more vaccines, while low-income countries continue to wait.

    Every day, there are six times more boosters administered globally than primary doses in low-income countries.

    This is a scandal that must stop now. "

    Not confused jed, your experts have not used a booster against Omicron yet but you say a third will restore protection. Really? Show me that data. You made the mistake of providing a wrong statement of restoration!

    Quote from JedRothwell

    No, that is not enough. Suppose an unvaccinated young person infects a 65-year-old with a breakthrough case. That 65-year-old is more likely to die than the unvaccinated 30 year old. By not vaccinating, young adults put the rest of society, including children and old people, at great risk. For no reason. Hundreds of thousands of people will die from breakthrough cases if young people do not get vaccinated.


    See:


    https://www.axios.com/age-coro…a9-894b-4b894dc017c9.html

    Yea, but Germany and Holland? We heard that vaccination is not so god at preventing infection, just to make it milder. What is R among the vaccinated after 4-7 months time?

    and unvaccinated?.

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