When anti-S(pike) antibodies against Omicron can no longer sustain the narrative, why not resort to T cells?

When anti-S(pike) antibodies against Omicron can no longer sustain the narrative, why not resort to T cells?

Note that views expressed in this opinion article are the writer’s personal views and not necessarily those of TrialSite.by Geert Vanden Bossche I

trialsitenews.com

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

by Geert Vanden Bossche

I recently came across an article in which the author had hoped would serve as a plausible immunological explanation as to why Omicron manifests itself as a mild illness and as a rational for continuing the mass vaccination program (T Cells Might Be Our Bodies’ Best Shot Against Omicron). I’ve repeatedly debunked arguments of those claiming an important role of cross-reactive T cells in controlling spread of SARS-CoV-2 variants, yet T cells are once again put in the spotlight as a last resort to rescue the vaccine narrative!

Now that we have a variant that has largely become resistant to neutralization by vaccinal Abs, some immunologically naïve people are leading us to believe that vaccine-induced T cells explain Omicron’s mild infectious behavior and why “the capacity of the immune system to limit the spread of the virus would still be preserved.” Their story attempts to build the case for people to remain confident that they’re at much lower risk of getting seriously ill if they’re vaccinated. Lucky enough, we’re not mainstreamers who buy stories that are rooted in biased analysis, such as those reporting protection of vaccinees against severe disease based on assessments involving hospitalized patients only! We don’t swallow stories that are not based on sound scientific grounds or that suffer from confounding bias.

The author of this article is confusing T cell-mediated immune recognition with T cell-mediated cytolysis. There is no evidence that natural coronavirus (CoV) infection or any C-19 vaccine induces fully functional cytolytic T memory cells in vivo (1, 2). As a result, CoV-specific T cells do not provide sterilizing immunity and therefore cannot prevent viral transmission.

A multitude of studies have shown that T cells are involved in SARS-CoV-2 infection (3, 4, 5, 6-11), but the contribution of these responses to protection has largely remained elusive. A number of these publications report cognate priming of cytokine-secreting SARS-CoV-2-specific CD4+ and CD8+ T cells as of an early stage of infection or disease onset. CD4+ T cell activity against any of the SARS-CoV-2 antigens correlates with the total amount of RBD[1]-specific antibodies (Abs) and CD8+ T cell activity, suggesting that antigen (Ag)-specific CD4+ T cells serve as helper cells for either RBD-specific antibody production or CD8+ T cell responses (10). The induction of T cells, in particular CD8+ T cells, has been associated with asymptomatic infection or enhanced recovery and prevention of progression to severe disease in symptomatically infected individuals (5, 12, 13). In asymptomatically infected individuals, CD8+ T memory cells against peptides conserved across coronaviruses were found to be far more abundant than T cells against peptides unique to SARS-CoV-2. However, asymptomatic infection implies prevention of productive infection or abrogation thereof at an early stage of infection. Such abrogation can only be effectuated by cytotoxic immune cells (i.e., NK cells or cytotoxic T cells [CTLs]), not by inflammatory cytokines secreted by T cells (e.g., IFN-γ, IL-2, TNF-α) as those cannot sterilize infectious virus or virus-infected cells. As far as T cells are concerned, there is not a single shred of evidence indicating ex vivo killing of CoV peptide-loaded or CoV-infected target cells by T cells isolated from previously asymptomatically or symptomatically infected individuals (as this would require CoV-specific T memory cells to be endowed with cytotoxic capacity). It is, therefore, unlikely that the occurrence of asymptomatic infection is due to expansion of these T cells as a result from previous exposure to seasonal human CoVs or other betacoronaviruses of clinical importance to humans (e.g., SARS-CoV-1, MERS-CoV). The observed expansion more likely results from rapid clearance of SARS-CoV-2 by innate Abs and/ or NK cells, thereby resulting in short-lived exposure of the immune system to the virus (14) and hence, favoring induction of CD8+ T cells that are capable of recognizing immunodominant CD8+ T cell epitopes comprised within early CoV proteins[2] (i.e., ORF-1) and phylogenetically conserved (5). As common cold CoVs are endemic, it would also be difficult to understand how previous exposure to these viruses would lead to better protection against SARS-CoV-2 in children than in older age groups. A higher incidence of infection with common cold CoVs has been reported for children, but those data are based on serology tests, which are likely to vastly underestimate asymptomatic infections. The lower susceptibility of children to SARS-CoV-2 is thought to be due to their more abundant levels of innate Abs (15). These Abs are mostly of IgM isotype and featured by broad reactivity and a variable affinity.

The association between the preferential recruitment of cross-reactive, cytokine-secreting MHC class I-restricted CD8+ T memory cells and enhanced recovery from C-19 disease and mitigation of disease in symptomatically infected individuals (5, 12) suggests that these cells serve a role as noncognate helper cells assisting CTL-mediated killing of virus-infected cells. Upon recognition of their cognate Ag, these T cells would be recalled and provide inflammatory mediators that mediate activation of CoV-specific cytotoxic T cells devoid of memory markers and thereby enhance viral clearance in symptomatically infected patients (see below). Activation of such cytotoxic T cells could, therefore, expedite recovery from symptomatic infection and thereby decrease the likelihood of progression to severe disease. As SARS-CoV-2-specific T memory cells recognize T cell peptides across a broad spectrum of distinct CoVs, previous infection with a given CoV species could enhance recovery from disease and avoid a more severe course of C-19 illness.

Furthermore, if in vivo priming of previously CoV-primed cross-reactive memory T cells were responsible for Omicron’s mild course of C-19 disease, one wonders why cross-reactive T memory cells were not already our bodies’ best shot at attenuating disease caused by the Delta variant.

Based on all of the above, it is reasonable to conclude that CoV-specific T cells cannot be responsible for the predominantly mild course of infection caused by Omicron. The author’s interpretation of published SARS-CoV-2-related T cell data being supportive of C-19 vaccination is also completely at odds with the observation that CoV-specific cytokine-secreting CD8+ T memory cells, the preferential recruitment of which is correlated with enhanced recovery and mitigation of disease symptoms, are not primarily directed at the spike (S) protein (3, 5, 11-13, 16) and that severe C-19 disease is rare in the unvaccinated as well. Consequently, it is a complete misconception that vaccination with S-based C-19 vaccines would provide any advantage over natural exposure, even in terms of promoting recall of a T cell-mediated adjuvant effect.

The statement, therefore, that Omicron causes a milder course of disease in vaccinees and that vaccination will significantly lower the risk of getting seriously ill defies all immuno-‘logic’ and reason. In her blind excitement about mass vaccination, the author rages on pretending that more vaccination is needed to prevent immune escape of dominant SARS-CoV-2 T cell epitopes (“too many people around the world remain unvaccinated!”). Interestingly enough, she seeks supportive evidence from a reference which actually advises for caution in regards to the impact of population-level immunization (“As vaccine and naturally acquired population immunity increase further, the frequency of variants we have described should be monitored globally, as well as further changes arising within all immunodominant T cell epitopes”; 17)

In conclusion, it is fair to say that the more plausible explanation for Omicron’s mild behavior lies in its escape from neutralizing vaccinal Abs which prevents the latter from suppressing relevant innate Abs (18, 19). In contrast, non-neutralizing, short-lived Th-independent anti-S Abs that unvaccinated acquired upon previous asymptomatic/ mild infection may now be a better match to Omicron’s S protein than the vaccinal Abs targeted at the S protein of the original Wuhan strain. This might explain why a small part of the unvaccinated population may currently see their relevant innate Abs being suppressed to an extent that makes them more susceptible to severe disease than the vaccinated. However, as already reported, this is likely to change when Omicron becomes dominant; high infectious pressure exerted by the predominantly circulating Omicron variant would primarily suppress poorly trained innate immune Abs in vaccinees (20).

Lastly, no matter how hard some vaccine producers will try to induce CoV-specific T cell responses by incorporating conventionally selected T cell epitopes in their new candidate vaccines, they won’t be able to induce a universally protective T cell response capable of abrogating and blocking viral transmission in vaccinated target populations. Even though equipped with an impressive arsenal of conserved CoV-specific T cell epitopes, C-19 vaccines targeting S protein will still be prone to expediting the expansion in prevalence of more infectious immune escape variants when used in a pandemic. Furthermore, recovery from symptomatic infection and protection against severe disease in these individuals will be no better than that of naturally exposed unvaccinated subjects. I, therefore, firmly disagree with those pretending that conventional T cell-oriented vaccines could allow for controlling the C-19 pandemic (21). On the contrary, loading C-19 vaccines with immunodominant T cell epitopes could potentially promote immune escape from T cell recognition as has recently been described to occur as a result of population-level immune pressure (17). This may ultimately result in loss of the above-described T cell-mediated mitigation of disease severity in both vaccinated and nonvaccinated individuals who contract symptomatic infection. Personally, I do not believe that non-sterilizing vaccine candidates comprising a multitude of different SARS-CoV-2-specific T cell epitopes will be capable of preventing an expansion of variants that also escape T cell recognition when used in a mass vaccination program. It seems that many of us have forgotten about the myriad of miserable clinical failures previously reported for HIV-1 vaccine candidates using a panoply of constructs that resulted from all kinds of sophisticated T cell epitope engineering. Suboptimal immune pressure in a limited number of chronically virus-infected patients may, indeed, have the same effect on the virus’ evolutionary capacity as suboptimal immune pressure exerted by the majority of a population when exposed to an acute viral infection.

This being said, recovery from CoV-disease, an acute viral infection known to be ‘self-limiting’ in nature, is clearly not restricted by the genetic MHC[3] background of the host. It is, therefore, conceivable that viral clearance leading to recovery from CoV disease is mediated by cytotoxic T cells (CTLs) that are triggered by upregulation of a universal immunodominant CTL epitope that is presented on cell surface-expressed MHC class I molecules without imprinting immunological memory. Such a universal immunodominant CTL epitope has, indeed, been identified within the S2 subunit of Coronaviruses (22). A vaccine designed in a way that enables induction of cytotoxic T memory cells against this universal epitope (i.e., SF[A]IEDLLF) would hold great promise in protecting vaccinees from productive infection, thereby conferring sterilizing immunity and hence, enable herd immunity.

References:

https://www.nature.com/articles/s41586-021-04280-x_reference.pdf

2. https://www.pnas.org/content/pnas/117/39/24384.full.pdf

3. https://www.ncbi.nlm.nih.gov/l…s/PMC7574860/pdf/main.pdf

4. https://www.ncbi.nlm.nih.gov/l…s/PMC7237901/pdf/main.pdf

5. https://www.nature.com/articles/s41586-020-2550-z.pdf

6. https://www.ncbi.nlm.nih.gov/l…PMC7574914/pdf/370_89.pdf

7. https://www.nature.com/articles/s41590-020-00808-x.pdf

8. https://www.nature.com/articles/s41590-020-0782-6.pdf

9. https://www.nature.com/articles/s41591-020-01143-2.pdf

10. https://www.cell.com/action/sh…S2666-3791%2821%2900015-X

11. https://www.cell.com/action/sh…S0092-8674%2820%2931235-6

12. https://www.science.org/doi/10.1126/sciimmunol.abg5669

13. https://www.ncbi.nlm.nih.gov/l…s/PMC7826084/pdf/main.pdf

14. https://www.ncbi.nlm.nih.gov/l…0/pdf/fimmu-11-610300.pdf

15. https://www.ncbi.nlm.nih.gov/l…s/PMC7202830/pdf/main.pdf

16. https://www.ncbi.nlm.nih.gov/l…s/PMC8139264/pdf/main.pdf

17. https://www.ncbi.nlm.nih.gov/l…s/PMC8552693/pdf/main.pdf

18. https://trialsitenews.com/like-a-virginuntouched-forever/

19. https://www.voiceforscienceand…icron-give-the-final-blow

20. https://trialsitenews.com/omic…-calm-before-the-tsunami/

21. https://www.nature.com/articles/s41577-021-00625-9

22. https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC2708636/

[1] RBD: Receptor-binding domain

[2] Those are produced first in coronavirus-infected cells and are required for the formation of the viral replicase–transcriptase complex that is essential for the subsequent transcription of the viral genome

[3] MHC: Major histocompatibility complex

“Omicron up to 70% less likely to cause hospitalization than delta variant, UK government study finds”.

Small sample size but heading in the right direction as hoped.

Quote from Fm1

In Japan, researchers have also examined factors like weather, cyclical patterns in the spread of the virus, and potential past exposure to mild coronavirus variants that may have led to the low case and death counts. Experts have identified potential genetic characteristics among the Japanese that may have led to a stronger immune system response to the coronavirus, but said there needs to be more research to draw definitive conclusions.

Yes. That has been widely reported in the Japanese mass media. Perhaps there is something to it, but we know for sure that the Japanese population can be infected by COVID with exponential increases, because that is what happened in 2020 before vaccinations began. Even if the population is somewhat more resistant to the disease than other populations, the difference is not large. Without the vaccines, masking and other steps, many thousands more people would have died.

Meanwhile - on a more pertinent topic.

So tracking Santa via NORAD I cannot help but observe that the speed of his sleigh breaks with the standard laws of physics.

I don't know if Wyttenbach might be able to provide an explanation but is it possible that Santa is actually using some kind of LENR based propulsion?

Merry Christmas to everyone on LENR Forum and thanks for your agreements and disagreements. Thank God LENR Forum is not just an echo chamber like some sites.

And special thanks to the Mods for all their work during the year.

Province of Ontario, Canada Follows Johns Hopkins University, Embracing Fluvoxamine as COVID-19 Therapy

Province of Ontario, Canada Follows Johns Hopkins University, Embracing Fluvoxamine as COVID-19 Therapy

The COVID-19 pandemic exposed on a global scale a multitude of challenges, including the drug development system itself—the bias toward advanced,

trialsitenews.com

The COVID-19 pandemic exposed on a global scale a multitude of challenges, including the drug development system itself—the bias toward advanced, high-cost novel vaccines and therapies over the aggressive investigation into existing, U.S. Food and Drug Administration (FDA) approved, so-called repurposed therapies. But some breakthroughs were made, thanks to a group called the COVID-19 Early Treatment Fund (CTEF). Formed by Silicon Valley tech entrepreneur Steve Kirsch, this group sponsored the initial clinical trials that led to positive results; and ultimately, a major clinical trial funded by Fast Grants and the Rainwater Charitable Foundation called the TOGETHER trial. McMaster University’s Dr. Edward Mills led the multinational study with the study results published in The Lancet on October 27, 2021. With little to no media coverage, the Canadian and Brazilian led team found that the use of fluvoxamine (100 mg twice daily for 10 days) by high-risk outpatients with early diagnosed COVID-19 reduced hospitalization by 32%. Moreover, Kirsch has shared previously with TrialSite that study data indicate participants participating in the early fluvoxamine research interestingly, haven’t manifested long COVID-19. Finally, an expert panel set up to guide Canada’s most populated province formally endorsed the drug for COVID-19. This economical antidepressant represents a compelling option now in the war against COVID-19. In this case, the drug is considered for mild COVID-19 patients. The goal, of course, is to keep individuals out of the hospital. Last month a prominent group within Johns Hopkins University (including the globally ranked hospital) also included fluvoxamine in their COVID-19 treatment guideline. Could America’s National Institutes of Health (NIH) be next?

Ontario obtained what is known as the Science Table. An advisory group called the Ontario COVID-19 Science Advisory Table, this group of scientific experts as well as health system heads get together on an ongoing basis to study, evaluate and track emerging evidence linked to the COVID-19 pandemic in a bid to better inform the province.

An independent group hosted by the Dalla Lana School of Public Health, funding for the Scientific Director as well as the Secretariat of the group originates from the Dalla Lana School of Public Health and Public Health Ontario.

The Implication

As reported by Avis Favaro at CTV News, the selective serotonin reuptake inhibitor (SSRI) usually prescribed for depression or obsessive-compulsive disorders now can be considered by physicians in Canada’s most populated province.

And the timing is right. This latest Omicron variant-driven wave of infections shattered previous records during the pandemic. Recently, on December 23rd, 20,699 infections were reported. Thankfully, the death rate in Canada is nowhere near close to levels seen during the first and second waves of the pandemic. But nonetheless, the danger of hospitalization and death is high.

An associated professor of medicine at McMaster University Dr. Menaka Pai also happens to co-chair the Ontario COVID-19 Science Advisory Table, sharing with Ms. Favaro, “Right now, we’re in a really unprecedented wave of Omicron and we have just a staggering number of patients getting infected.” In relation to fluvoxamine, Dr. Pai declared “Our goal is to keep them safe, to keep them out of the hospital, and also to preserve our scarcest resource, which I would say is our hospital beds.”

Co-Principal Investigator Mills also went on the record with the Canadian media emphasizing to the public “It’s a very large treatment effect, one that hasn’t been observed for any drug yet.”

Johns Hopkins on Board

Johns Hopkins University has also embraced the repurposed drug for COVID-19 patients. Specifically, the JHMI Clinical Recommendations for Pharmacologic Treatment of COVID-19 updated on November 16, 2021, represents a joint effort between the COVID-19 Treatment Guidance Writing Group of Johns Hopkins University and the Johns Hopkins Hospital COVID-19 Treatment Guidance Working Group.

This influential group now includes fluvoxamine as an endorsed treatment for patients within seven days of symptom onset, excluding individuals pregnant and in the third trimester.

Conclusion

As part of the TrialSite Advisory Committee, Dr. Michael Goodkin recently declared fluvoxamine is “grossly underutilized.” With a material reduction in hospitalization rates (which impacts mortality rates), low cost, and widely available in the face of a massive Omicron-based wave of infections in Canada the medical leadership in Ontario just made a critically important move. CTV News reports other provinces In Canada now also have the drug as a candidate for endorsement.

Meanwhile, one of the most prestigious academic medical centers on the planet, Johns Hopkins Hospital, offers the therapy in certain circumstances.

Other health systems, academic medical centers, and hospitals should consider following

Happy Christmas for all the Cold Fusionners all over the world!

lenr-forum.com/attachment/19451/

Chief medical officer here says not a matter of if, but when, everyone will be exposed to omicron.

Wouw!!

South Africa's ward is going down already. High care by about 7% from yesterday!

Omicron seems to be really harmless not only 70% Obviously as they say. 3 days in hospital average!

Quote from Paradigmnoia

Chief medical officer here says not a matter of if, but when, everyone will be exposed to omicron.

Main problem. Most will not even note it. We(PCR) here miss 5 out of 6 cases....

I missed this strand of pro-ivermectin antivaxxer lies. Supported here by a few people who are perhaps not looking much at the whole story.

And for anyone supporting the FLCC "Ivermectin works - it is a pharma conspiracy to say it does not" line, but not supporting the antivaxxer "mRNA side effects are much larger than the regulators (who document them in excruciatingly careful detail) say they are" one.

Then I'll happily avoid antivaxxer and call this raft of distortions and lies "ivermectin-crazy".

To be clear: I do not know whether ivermectin works against COVID (a bit). The big RCTs testing have not pre-announced (except one, pre-announcing negative but on relatively small results). That means it cannot be strongly positive. But a small positive effect - say 10% on mortality - sure. It is quite possible. As is a small negative effect.

Also: I'm pretty neutral on whether ivermectin-carzy doctors should be allowed to prescribe ivermectin. I think in most places they are. It is a slippery slope as the history of the medical profession shows - doctors find it really easy to go on giving non-working and even harmful cures to patients, absolutely convinced they work. Anyway that is not the issue here.

The issue here is how ivermectin-crazies go about hurting honest scientists who change their mind.

It is a bit like religions: the ones who get targeted are those who were believers but give it up.

Unlike politicians - for scientists changing one's mind - or just being unsure - goes with the job. If you can't do it you should not be a scientists.

The two singled out in this way are Chaccour and Hill.

Chaccour pioneered the use of ivermectin as an antiparasitic. Who knows more about it than anyone else. He is still hopeful it might work, but says he cannot know till the big RCT tests come back. The score on those is one negative (early - inconclusive) others not yet done.

Chaccour got a whole load of abuse (for running a dishonest trial) when his own ivermection trial returned negative results. He was still at that time positive on ivermectin - but positive in a rational; "we can't tell yet, but there is still hope" way. That was not good enough for the ivermectin-crazies - who believe anyone not agreeing with their "it is obvious ivermectin works" mantra is a genocidal killer. They therefore are strongly against RCTs on ivermectin. They think it is unethical to withhold ivermectin from the placebo arm, when it is certain ivermectin works.

Some will see the irony here.

Hill did a metastudy which based on inclusion of Elgazaar was initially positive on ivermectin. At that time Hill was positive on ivermectin.

When Elgazaar was found fraudulent and (forced to be) retracted, Hill, as was proper, said he would republish his study.

He republished it - excluding studies at high risk of bias (fool me twice, shame on me).

Meta-analysis of Randomized Trials of Ivermectin to Treat SARS-CoV-2 Infection - PubMed

Ivermectin is an antiparasitic drug being investigated for repurposing against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Ivermectin showed…

pubmed.ncbi.nlm.nih.gov

It was negative (neutral) on ivermectin. As a result Hill joins the ivermectin-crazy social media hit list:

‘I hope you die’: how the COVID pandemic unleashed attacks on scientists

Dozens of researchers tell Nature they have received death threats, or threats of physical or sexual violence.

www.nature.com

Some aspects of COVID-19 science have become so politicized that it is hard to mention them without attracting a storm of abuse. Epidemiologist Gideon Meyerowitz-Katz at the University of Wollongong in Australia, who has gained a following on Twitter for his detailed dissection of research papers, says that two major triggers are vaccines and the anti-parasite drug ivermectin — controversially promoted as a potential COVID-19 treatment without evidence it was effective. “Any time you write about vaccines — anyone in the vaccine world can tell you the same story — you get vague death threats, or even sometimes more specific death threats and endless hatred,” he says. But he’s found the passionate defence of ivermectin surprising. “I think I’ve received more death threats due to ivermectin, in fact, than anything I’ve done before,” he says. “It’s anonymous people e-mailing me from weird accounts saying ‘I hope you die’ or ‘if you were near me I would shoot you’.”

Andrew Hill, a pharmacologist at the University of Liverpool’s Institute of Translational Medicine, received vitriolic abuse after he and his colleagues published a meta-analysis in July. It suggested ivermectin showed a benefit, but Hill and his co-authors then decided to retract and revise the analysis when one of the largest studies they included was withdrawn because of ethical concerns about its data (A. Hill et al. Open Forum Inf. Dis. 8, ofab394; 2021). After that, Hill was besieged with images of hanged people and coffins, with attackers saying he would be subject to ‘Nuremberg trials’, and that he and his children would ‘burn in hell’. He has since closed his Twitter account.

I'd wish this site paid more attention to science and less to conspiracy theories...

Ivermectin debacle exposes flaws in meta-analysis methodology

Health researchers warn that taking studies at face value is a luxury that they can no longer afford

www.chemistryworld.com

Hill says his group followed the best practice guidelines for assessing bias. ‘There are safeguards to make sure the studies [in meta-analyses] are of good quality, but they don’t work if people lie in their replies to questions,’ says Hill. ‘I’ve worked on HIV for 30 years. We don’t get fraud. We get trustworthy doctors, from a whole range of countries.’

‘The people who’ve done these meta-analyses haven’t stuffed up,’ Sheldrick says. ‘They haven’t deviated from accepted standards or made big mistakes.’ Instead, there is a fundamental flaw in the approach, and investigators need to ask those running trials to send them their data, the letter states.

‘Any study for which authors are not able or not willing to provide suitable anonymised [individual patient data] should be considered at high risk of bias for incomplete reporting and/or excluded entirely from meta-syntheses,’ the letter notes. There may, however, be difficulties in obtaining patient data from government agencies, and pharmaceutical companies may want to retain it as part of their intellectual property.

The fraud has had repercussions, with people against or concerned about Covid-19 vaccines resorting to what is an unproven treatment. Some even took ivermectin intended for horses. Moreover, proponents of ivermectin on social media platforms have suggested unusually high doses.

‘Some recommend 3000µg of ivermectin over five days,’ notes Sheldrick, who says Australia has some experience with prescribing this drug for parasitic infections such as scabies. ‘That is 20 times what we give for river blindness, where we give a single dose of 150µg.’

Meanwhile, large-scale clinical trials such as Remap-Cap, which evaluates multiple repurposed interventions, are continuing and may yet show a benefit from ivermectin. But for now, there is no evidence showing that it works for Covid-19, and strong evidence for many early trials being untrustworthy.

What you do not hear form the ivermectin-crazies, the context, and which underlies what MOST PEOPLE who study evidence with open minds think about ivermectin:

Misleading clinical evidence and systematic reviews on ivermectin for COVID-19

Since WHO declared the COVID-19 as a pandemic,1 2 healthcare systems all over the world have focused their efforts on limiting the spread of SARS-CoV-2, and…

ebm.bmj.com

An important controversial point to consider in any rationale is the 5 µM required concentration to reach the anti-SARS-CoV-2 action of ivermectin observed in vitro,17 which is much higher than 0.28 µM, the maximum reported plasma concentration achieved in vivo with a dose of approximately 1700 µg/kg (about nine times the FDA-approved dosification).24 25 In this sense, basic fundamentals for assessing ivermectin in COVID-19 at a clinical level appear to be insufficient. Among other reasons, we believe this might have led WHO to exclude ivermectin from its Solidarity Trial for repurposed drugs for COVID-19,12 which raises questions about the pertinence of conducting clinical studies on ivermectin.

Nevertheless, assessments of ivermectin as prophylaxis or treatment for mild to severe COVID-19 continue being published in preprints26 27 and protocol repositories,28 29 which do not follow the recommended process to ensure quality standards in publications; whereas peer-reviewed reports (both observational and experimental studies) are slowly emerging, yet methodologically limited by heterogeneity in population receiving ivermectin, dosis applied and uncontrolled cointerventions.28–30 Similarly, other studies that can be rapidly retrieved in ClinicalTrials.gov, medRxiv and MEDLINE make up a quite heterogeneous body of evidence31–33 (including ivermectin as intervention, but with different underlying clinical questions), among other issues that do not contribute to the certainty of evidence—according to the systematic reviews that we comment on below.

Up to February 2021, the PAHO identified twenty two ivermectin randomised clinical trials through a rapid review of current available literature.34 There is considerable heterogeneity in the population receiving ivermectin, with studies administering it to family contacts of confirmed COVID-19 cases as a prophylactic measure29 and other studies using ivermectin for treatment of mild and moderate infected cases28 or even severe hospitalised patients.30 Applied dosis and outcomes of interest were also highly variable. Additionally, patients also received various cointerventions, and control groups received different kinds of comparators ranging from placebo or no intervention to standard care or even hydroxychloroquine. The authors claim that pooled estimates suggest beneficial effects with ivermectin, but the certainty of the evidence was very low due to high risk of bias and small number of events throughout the included studies. Most study results have been made publicly available as preprints or unpublished, with no peer review or formal editorial process. Others incorporated their results only in the clinical trial register, but nearly half of these randomised clinical trials had not been registered. Registering clinical trials before they begin and making results available fulfils a large number of purposes, like reducing publication and selective outcome reporting biases, promoting more efficient allocation of research funds and facilitating evidence syntheses that will inform stakeholders and decision-makers in the future.

A recently published systematic review and network meta-analysis35 compared the efficacy and safety of pharmacological interventions for COVID-19 in hospitalised patients. It included 110 studies (78 published and 38 unpublished) with 40 randomised clinical trials and 70 observational studies. Based on observational data, they found that high-dose intravenous immunoglobulin, ivermectin and tocilizumab were associated with reduced mortality rate in critically ill patients. None of the analysed drugs was significantly associated with increased non-cardiac serious adverse events compared with standard care, but the overall certainty of the evidence was very low in all outcomes and reduced the ability for recommendation.

Different websites (such as https://ivmmeta.com/, https://c19ivermectin.com/, https://tratamientotemprano.org/estudios-ivermectina/, among others) have conducted meta-analyses with ivermectin studies, showing unpublished colourful forest plots which rapidly gained public acknowledgement and were disseminated via social media, without following any methodological or report guidelines. These websites do not include protocol registration with methods, search strategies, inclusion criteria, quality assessment of the included studies nor the certainty of the evidence of the pooled estimates. Prospective registration of systematic reviews with or without meta-analysis protocols is a key feature for providing transparency in the review process and ensuring protection against reporting biases, by revealing differences between the methods or outcomes reported in the published review and those planned in the registered protocol. These websites show pooled estimates suggesting significant benefits with ivermectin, which has resulted in confusion for clinicians, patients and even decision-makers. This is usually a problem when performing meta-analyses which are not based in rigorous systematic reviews, often leading to spread spurious or fallacious findings.36

Concluding, research related to ivermectin in COVID-19 has serious methodological limitations resulting in very low certainty of the evidence, and continues to grow.37–39 The use of ivermectin, among others repurposed drugs for prophylaxis or treatment for COVID-19, should be done based on trustable evidence, without conflicts of interest, with proven safety and efficacy in patient-consented, ethically approved, randomised clinical trials.

‘I hope you die’: how the COVID pandemic unleashed attacks on scientists Dozens of researchers tell Nature they have received death threats, or threats of physical or sexual violence.

They wouldn't get it, if they would act like scientist Dr. Jonas Salk for example. Jonas Salk didn't create a polio virus during his research - he found its cure instead. His research was paid from public money so that he gave his vaccine to people for free. And his vaccine really worked and it was harmless even from long term perspective.

The contemporary Covid vaccines are exactly the opposite of all of it so that the people rightfully feel they're getting cheated and f*cked with scientists at so many levels. It's a matter of quality of their research, not quantity.

Quote from Zephir_AWT

They wouldn't get it, if they would act like scientist Dr. Jonas Salk for example. Jonas Salk didn't create a polio virus during his research - he found its cure instead. His research was paid from public money so that he gave his vaccine to people for free. And his vaccine really worked and it was harmless even from long term perspective.

Not exactly harmless in the early years...

In April 1955 more than 200 000 children in five Western and mid-Western USA states received a polio vaccine in which the process of inactivating the live virus proved to be defective. Within days there were reports of paralysis and within a month the first mass vaccination programme against polio had to be abandoned. Subsequent investigations revealed that the vaccine, manufactured by the California-based family firm of Cutter Laboratories, had caused 40 000 cases of polio, leaving 200 children with varying degrees of paralysis and killing 10.

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In April 1955 more than 200 000 children in five Western and mid-Western USA states received a polio vaccine in which the process of inactivating the live virus proved to be defective. Within days there were reports of paralysis and within a month the first mass vaccination programme against polio had to be abandoned. Subsequent investigations revealed that the vaccine, manufactured by the California-based family firm of Cutter Laboratories, had caused 40 000 cases of polio, leaving 200 children with varying degrees of paralysis and killing 10.

Thank You for pointing it out. Actually polio vaccines got recently quite controversial because they increase number of mutations of polio virus in similar way like covid vaccines now and inactivated poliovirus of vaccine can get occasionally reactivated. The analogy with breakthrough infections with long used antibiotics arises here. I just wanted to say, that people judge scientists by their momentary results and when they face hockey stick graph of side effects, they get naturally upset with it.

Judgment day: Sweden vindicated

Austria, one of the most repressive European countries during the coronavirus pandemic, has recently overtaken Sweden in terms of total covid mortality,…

swprs.org

Yes, Sweden again. This time in comparison to Austria, and how each has done against COVID. Sweden with it's relatively laissez faire policy, and Austria with it's more oppressive approach.

Quote from THHuxleynew

Andrew Hill, a pharmacologist at the University of Liverpool’s Institute of Translational Medicine, received vitriolic abuse after he and his colleagues published a meta-analysis that has been written by the FM/R/J/B mafia and published under his name.

He got a 40 million reward research contracts what usually includes a 2% personal share....

Adrew Hills simply is a criminal FM/R/B mafia member that seems to be a fellow of our clown. He is corrupt down to his bones and certainly will loose his job after the corona story is at its end.

He did commit fraud by allowing others to publish under his name without mention the contributors.

But clowns like other clowns.

Ivermectin reduces death in ICU by about 80%. All my double vaxx US friends know this and certainly would never go in a regular hospital ... But I recommend these hospitals for clowns that like to get a funny treatment...

Total failure of vaccines!

All vaccine terror states see a record increase in cases with over 260'000 in USA for December 23th, same for UK, Israel etc...

We have to note that vaccines have no influence on the pandemic as these vaccines are fake and in fact a rebranded cancer chemo of experimental status.

Most victims of Omicron are 2x/3x vaxx as these are immune suppressed and own misfitting antibodies. Luckily Omicron is a very "mild" virus. Not in the manner of a mild vaccine injury like eye thromboses a heart scarf...Most people that get omicron need 1-2 days for a recovery and most don't even notice the infection.

But the mafia sees the fishes leaving the net and tries to reinvent fairy tales of unknown highest danger... o yeh for the portfolio of course....

Quote from Zephir_AWT

They wouldn't get it, if they would act like scientist Dr. Jonas Salk for example. Jonas Salk didn't create a polio virus during his research - he found its cure instead. His research was paid from public money so that he gave his vaccine to people for free. And his vaccine really worked and it was harmless even from long term perspective.

The contemporary Covid vaccines are exactly the opposite of all of it so that the people rightfully feel they're getting cheated and f*cked with scientists at so many levels. It's a matter of quality of their research, not quantity.

So let me be clear. When scientists try to solve an urgent problem, and generate something that works better than what they originally thought would be possible in that time scale, better than has ever been done before, you think it is fair they get death threats?

In what world is it fair that anyone gets death threats!

And in what world can scientists not get death threats if they have to meet some impossible standard of Zephir expectation?

Respiratory virusses, like Flu have vaccines typically 50% effective.

COVID vaccines (some) were 95% effective against original, still 70% effective against delta. And even 75% (not sure how good that figure is) against omicron.

In terms of how long they last: Flu jabs last 6 months.

In terms of how safe they are: slightly more reactogenic than you'd like, but side effects more carefully monitored than anything in history at levels much lower than unvaccinated COVID disease effects for all ages down to 12.

COVID jabs last (neutralising) probably 1 year (original) 5 months (delta) 2-3 months (omicron).

And, even after neutralising ab effect is gone, the vaccines continue to reduce severe disease.

In terms of societal effect: Flu vaccines do not stop Flu waves returning. For COVID vaccines to do that is aspitational.

Those figures may be a cup half full to you, but are they not better than we might expect, and certainly they put is in a much better position than we'd be without it?

Doubtless in 20 years time scientists will get death threats because geoengineering solutions to climate change, while partially working, do not stop a lot of baked changes: and you will say that is expected because they do not have a perfect solution.

THH

Quote from Wyttenbach

Total failure of vaccines!

All vaccine terror states see a record increase in cases with over 260'000 in USA for December 23th, same for UK, Israel etc...

We have to note that vaccines have no influence on the pandemic as these vaccines are fake and in fact a rebranded cancer chemo of experimental status.

This is wrong in so many ways. And sort-of clever because it mixes straw men and lies.

Vaccines have influenced the pandemic profoundly. They have flattened and in some cases eliminated given variant waves. They juts have not made COVID go away. We would have needed 80% global coverage very quickly for that. It was never going to happen. No-one said it would. I think a few optimists said it might. Governments obviously did not believe it, because they did not fund the promised global vaccine rollout. And actually I mostly agree. Even with vaccine availability for all I don't think it would have been possible.

More, even with no change to pandemic they have turned COVID from a society-breaking disease into something like a severe Flu that we can cope with.

I guess it makes sense you would not notice this. I remember you backing arguments that COVID was (except for a few very old people) no worse than Flu.

Of course - Flu is nasty - which is why we have Flu vaccines even though they are only 50% effective at preventing infection. For many they save lives turning a killer disease into a bad cold.

But COVID now, for countries with vaccines, is infinitely better than 1.5 years ago. Which is why the UK, with a government absolutely not wanting to do it, locked down last Christmas, not this Christmas. Even though COVID infection rate now is higher than its ever been.

It helps that omicron looks to be a bit milder (50% perhaps) than delta. But the vaccines make an 80% - 90% difference in effect, a lot more than that.