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The BMJ to Facebook—Stop Censoring Us and Shut Down Your Incompetent Fact-Checkers

The BMJ to Facebook—Stop Censoring Us and Shut Down Your Incompetent Fact-Checkers

Top Editors from the British Medical Journal (The BMJ) have a message for Mark Zuckerberg of Facebook: get your fact-checkers in line,

trialsitenews.com

Top Editors from the British Medical Journal (The BMJ) have a message for Mark Zuckerberg of Facebook: get your fact-checkers in line, ASAP. As part of one of the world’s oldest and most prestigious medical journals, the senior editors express real concern about third-party fact-checkers employed by Facebook/Meta. This complaint surfaces based on the issues of potentially fraudulent or faulty data associated with Pfizer contract research organization Ventavia.

TrialSite wrote that The BMJ authored a critical piece investigating bombshell evidence that poor practices and quality control issues surfaced during the Pfizer COVID-19 vaccine clinical trials. Meticulously researched based on whistleblower documentation, the critical review, authored by Paul Thacker in the peer-review journal, raised eyebrows if not more.

Facebook Censors

However, The BMJ soon would get a taste of what Facebook, Google, and others are doing to independent media platforms such as the TrialSite. Even though The BMJ is one of the most prominent medical journals and the information was rigorously peer-reviewed, strange things started occurring.

For example, readers would try to post some of the information on social media such as Facebook to share with their networks. But “some reported being unable to share it [the information].” Moreover, as it turns out, “Independent fact-checkers concluded, “This formation could mislead people.” Those individuals that were simply sharing this content, peer-reviewed from The BMJ, were warned by Facebook that “This information could mislead people.” Moreover, they were told, “Those trying to post the article were informed by Facebook that people who repeatedly share ‘false information’ might have their posts moved lower in Facebook’s News Feed.” In addition, some group administrators received notices from Facebook that the information was “partly false.”

Then readers were sent to a “fact check” performed by Lead Stories, a third-party fact-checker. Yet as possibly the top experts on the planet when it comes to medical research information, The BMJ now have to fact check the fact-checkers, much like TrialSite has continuously had to do, finding the fact-checkers are, of course, incorrect.

The BMJ editor’s note the following:

∙ It fails to provide any assertions of fact that The BMJ article got wrong

∙ It has a nonsensical title: “Fact Check: The British Medical Journal Did NOT Reveal Disqualifying And Ignored Reports Of Flaws In Pfizer COVID-19 Vaccine Trials”

∙ The first paragraph inaccurately labels The BMJ a “news blog”

∙ It contains a screenshot of our article with a stamp over it stating “Flaws Reviewed,” despite the Lead Stories article not identifying anything false or untrue in The BMJ article

∙ It published the story on its website under a URL that contains the phrase “hoax-alert”

Note The BMJ editors contacted Lead Stories but they stand resolute that they are not incorrect. Now Facebook flags The BMJ article.

An Incompetent Fact-Checking Regimen

Both Ms. Godlee and Mr. Abbasi have a message for Facebook—your fact-checkers are “incompetent.” The social network had better get their act together, is the message. While they are at it, they should be reminded that Jen Psaki was on the record that high-level White House operatives were feeding Facebook information as to what was misinformation versus credible real information. For reference, we include The Hill piece on Psaki’s comments. Perhaps The BMJ should put Ms. Psaki on their list too as well as whoever those “senior” White House staff were that were “suggesting” to offer Facebook help.

As Dr. Ron Brown, a TrialSite contributor, asked over the summer: Does White House Spread Misinformation about Spreading Vaccine Misinformation?

Authors

Fiona Godlee, editor in chief

Kamran Abbasi, incoming editor in chief

Rapid Response:

Open letter from The BMJ to Mark Zuckerberg

Dear Mark Zuckerberg,

We are Fiona Godlee and Kamran Abbasi, editors of The BMJ, one of the world’s oldest and most influential general medical journals. We are writing to raise serious concerns about the “fact checking” being undertaken by third party providers on behalf of Facebook/Meta.

In September, a former employee of Ventavia, a contract research company helping carry out the main Pfizer covid-19 vaccine trial, began providing The BMJ with dozens of internal company documents, photos, audio recordings, and emails. These materials revealed a host of poor clinical trial research practices occurring at Ventavia that could impact data integrity and patient safety. We also discovered that, despite receiving a direct complaint about these problems over a year ago, the FDA did not inspect Ventavia’s trial sites.

The BMJ commissioned an investigative reporter to write up the story for our journal. The article was published on 2 November, following legal review, external peer review and subject to The BMJ’s usual high level editorial oversight and review.[1]

But from November 10, readers began reporting a variety of problems when trying to share our article. Some reported being unable to share it. Many others reported having their posts flagged with a warning about “Missing context ... Independent fact-checkers say this information could mislead people.” Those trying to post the article were informed by Facebook that people who repeatedly share “false information” might have their posts moved lower in Facebook’s News Feed. Group administrators where the article was shared received messages from Facebook informing them that such posts were “partly false.”

Readers were directed to a “fact check” performed by a Facebook contractor named Lead Stories.[2]

We find the “fact check” performed by Lead Stories to be inaccurate, incompetent and irresponsible.

-- It fails to provide any assertions of fact that The BMJ article got wrong

-- It has a nonsensical title: “Fact Check: The British Medical Journal Did NOT Reveal Disqualifying And Ignored Reports Of Flaws In Pfizer COVID-19 Vaccine Trials”

-- The first paragraph inaccurately labels The BMJ a “news blog”

-- It contains a screenshot of our article with a stamp over it stating “Flaws Reviewed,” despite the Lead Stories article not identifying anything false or untrue in The BMJ article

-- It published the story on its website under a URL that contains the phrase “hoax-alert”

We have contacted Lead Stories, but they refuse to change anything about their article or actions that have led to Facebook flagging our article.

We have also contacted Facebook directly, requesting immediate removal of the “fact checking” label and any link to the Lead Stories article, thereby allowing our readers to freely share the article on your platform.

There is also a wider concern that we wish to raise. We are aware that The BMJ is not the only high quality information provider to have been affected by the incompetence of Meta’s fact checking regime. To give one other example, we would highlight the treatment by Instagram (also owned by Meta) of Cochrane, the international provider of high quality systematic reviews of the medical evidence.[3] Rather than investing a proportion of Meta’s substantial profits to help ensure the accuracy of medical information shared through social media, you have apparently delegated responsibility to people incompetent in carrying out this crucial task. Fact checking has been a staple of good journalism for decades. What has happened in this instance should be of concern to anyone who values and relies on sources such as The BMJ.

We hope you will act swiftly: specifically to correct the error relating to The BMJ’s article and to review the processes that led to the error; and generally to reconsider your investment in and approach to fact checking overall.

Best wishes,

Fiona Godlee, editor in chief

Kamran Abbasi, incoming editor in chief

The BMJ

Competing interests:

As current and incoming editors in chief, we are responsible for everything The BMJ contains.

References:

[1] Thacker PD. Covid-19: Researcher blows the whistle on data integrity issues in Pfizer's vaccine trial. BMJ. 2021 Nov 2;375:n2635. doi: 10.1136/bmj.n2635. PMID: 34728500. https://www.bmj.com/content/375/bmj.n2635

[2] Miller D. Fact Check: The British Medical Journal Did NOT Reveal Disqualifying And Ignored Reports Of Flaws In Pfizer COVID-19 Vaccine Trials. Nov 10, 2021. https://leadstories.com/hoax-a…-check-british-medical-jo...

[3]

Competing interests: As current and incoming editors in chief, we are responsible for everything The BMJ contains.

Pfizer says kids under 5 may not get shots until mid-2022 after trial found low-dose vaccine didn't work in kids aged 2-5

Pfizer says kids under 5 may not get shots until mid-2022 after trial found low-dose vaccine didn't work in kids aged 2-5

A low dose of Pfizer's vaccine worked well in babies, but not so well in 2- to 5-year-olds. It means toddlers may not get shots until mid-2022.

www.businessinsider.com

Pfizer says the company's ultra low-dose vaccine for babies and toddlers isn't necessarily strong enough to induce protection among 2-to-5 year-olds.

The baby shot is a 3 µg mRNA dose (kids aged 5-11 receive 10 µg, and adults get 30 µg).

Pfizer said rather than up the dosage for toddlers, they're evaluating giving a third dose after two months — a development that threatens to delay toddlers' shots.

Danish Study Finds Covid Vaccines May Cause Possible Heart Inflammation

Danish Study Finds Covid Vaccines May Cause Possible Heart Inflammation

The “Covid Crisis” has raised many questions not only about government readiness for a global pandemic but also about the medical industry itself.  The

trialsitenews.com

The “Covid Crisis” has raised many questions not only about government readiness for a global pandemic but also about the medical industry itself. The onset of the COVID pandemic pushed for a rush to find a vaccine for the disease. Then once vaccines were found, the rush was to get the population vaccinated without questioning the serum’s efficacy or safety. A recent study in Denmark found people vaccinated with Moderna may have a higher rate of heart inflammation. Don’t standard good clinical practices coupled with safety best practices apply with products such as these? Presently, the Moderna vaccine is on hold for anyone under 30 in Denmark as reported by TrialSite. Other Scandinavia nations have followed with halts for younger people.

A Danish study published in the British Medical Journal (BMJ) reports that both the Pfizer and Moderna vaccines are an effective treatment against coronavirus however the data from the study “suggests an association between SARS-CoV-2 vaccination and myocarditis and myopericarditis.” In other words, the vaccine may cause inflammation of the heart. One of the authors of the study, Anders Hviid, said the study’s findings do not generally “overshadow” the benefits of being vaccinated.

Close to 5 million Danes ages 12 and older participated in the study. The research took approximately one year from October of 2020 to October of 2021. Over three million of the participants were vaccinated with Pfizer and close to five hundred thousand were vaccinated with Moderna. Following the vaccination, the study found that 48 (1.34%) people who took the Pfizer shot developed myocarditis within 28 days of receiving the vaccine. Of the over 490 thousand participants who received the Moderna shot 21 (3.92%) people developed myocarditis within 28 days of getting the shot. The highest risk seemed to be for people between the age of 12-39 and occurred after the second dose was administered.

The study also found cases of myocarditis were higher in women ages 12-39 after being given the Pfizer vaccine. So, according to the study both vaccines have the potential to cause heart inflammation, though the percentage is four times higher with Moderna. The authors of the study were quick to point out the prevalence of these side effects were low and when it did happen people had “predominantly mild” experiences. The authors also said the unvaccinated carried a “greater health risk” of cardiac arrest and death as a result of contracting covid. One of the authors Anders Husby said the research “supports the overall benefits of such vaccination on an individual, societal, and global level.”

TrialSite News has published many articles on Pfizer and their “lack of transparency” regarding the possible safety impacts their vaccine may have upon the vaccinated population. According to one recent TrialSite article based on the information disclosed in a FOIA, over 1200 people have died after taking the Pfizer shot and women were 3 times more likely to suffer “adverse events” as a result of the Pfizer vaccine. Of course, this doesn’t mean that the vaccine caused the deaths but many of the mortality incidents were uncomfortably close to the vaccine administration. This somewhat coincides with the study conducted in Denmark. While there is no doubt COVID rushed the world into crisis, could the “rushed” vaccine solution lead to a bigger problem in the future

Quote from Fm1

Close to 5 million Danes ages 12 and older participated in the study. The research took approximately one year from October of 2020 to October of 2021. Over three million of the participants were vaccinated with Pfizer and close to five hundred thousand were vaccinated with Moderna. Following the vaccination, the study found that 48 (1.34%) people who took the Pfizer shot developed myocarditis within 28 days of receiving the vaccine. Of the over 490 thousand participants who received the Moderna shot 21 (3.92%) people developed myocarditis within 28 days of getting the shot. The highest risk seemed to be for people between the age of 12-39 and occurred after the second dose was administered.

48 / 3,000,000 = 0.0016% not 1.34%

21 / 500,000 = 0.0042% not 3.92%

?? Something not quite right with the TSN summary?

THH

Quote from THHuxleynew

48 / 3,000,000 = 0.0016% not 1.34%

21 / 500,000 = 0.0042% not 3.92%

?? Something not quite right with the TSN summary?

THH

Display More

Here, this should clear it up

Abstract

Objective To investigate the association between SARS-CoV-2 vaccination and myocarditis or myopericarditis.

Design Population based cohort study.

Setting Denmark.

Participants 4 931 775 individuals aged 12 years or older, followed from 1 October 2020 to 5 October 2021.

Main outcome measures The primary outcome, myocarditis or myopericarditis, was defined as a combination of a hospital diagnosis of myocarditis or pericarditis, increased troponin levels, and a hospital stay lasting more than 24 hours. Follow-up time before vaccination was compared with follow-up time 0-28 days from the day of vaccination for both first and second doses, using Cox proportional hazards regression with age as an underlying timescale to estimate hazard ratios adjusted for sex, comorbidities, and other potential confounders.

Results During follow-up, 269 participants developed myocarditis or myopericarditis, of whom 108 (40%) were 12-39 years old and 196 (73%) were male. Of 3 482 295 individuals vaccinated with BNT162b2 (Pfizer-BioNTech), 48 developed myocarditis or myopericarditis within 28 days from the vaccination date compared with unvaccinated individuals (adjusted hazard ratio 1.34 (95% confidence interval 0.90 to 2.00); absolute rate 1.4 per 100 000 vaccinated individuals within 28 days of vaccination (95% confidence interval 1.0 to 1.8)). Adjusted hazard ratios among female participants only and male participants only were 3.73 (1.82 to 7.65) and 0.82 (0.50 to 1.34), respectively, with corresponding absolute rates of 1.3 (0.8 to 1.9) and 1.5 (1.0 to 2.2) per 100 000 vaccinated individuals within 28 days of vaccination, respectively. The adjusted hazard ratio among 12-39 year olds was 1.48 (0.74 to 2.98) and the absolute rate was 1.6 (1.0 to 2.6) per 100 000 vaccinated individuals within 28 days of vaccination. Among 498 814 individuals vaccinated with mRNA-1273 (Moderna), 21 developed myocarditis or myopericarditis within 28 days from vaccination date (adjusted hazard ratio 3.92 (2.30 to 6.68); absolute rate 4.2 per 100 000 vaccinated individuals within 28 days of vaccination (2.6 to 6.4)). Adjusted hazard ratios among women only and men only were 6.33 (2.11 to 18.96) and 3.22 (1.75 to 5.93), respectively, with corresponding absolute rates of 2.0 (0.7 to 4.8) and 6.3 (3.6 to 10.2) per 100 000 vaccinated individuals within 28 days of vaccination, respectively. The adjusted hazard ratio among 12-39 year olds was 5.24 (2.47 to 11.12) and the absolute rate was 5.7 (3.3 to 9.3) per 100 000 vaccinated individuals within 28 days of vaccination.

Conclusions Vaccination with mRNA-1273 was associated with a significantly increased risk of myocarditis or myopericarditis in the Danish population, primarily driven by an increased risk among individuals aged 12-39 years, while BNT162b2 vaccination was only associated with a significantly increased risk among women. However, the absolute rate of myocarditis or myopericarditis after SARS-CoV-2 mRNA vaccination was low, even in younger age groups. The benefits of SARS-CoV-2 mRNA vaccination should be taken into account when interpreting these findings. Larger multinational studies are needed to further investigate the risks of myocarditis or myopericarditis after vaccination within smaller subgroups.

That clears it up, of course.... 48 out of 3.483.295 is NOT 1,34 % PERCENT. That would be indeed very bad, if more than 1 out of 100 vaccinated persons will develop myocarditis...

Merck’s Molnupiravir paper in NEJM contains fabricated data

Merck’s Molnupiravir paper in NEJM contains fabricated data

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

trialsitenews.com

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

by Leo Goldstein

Merck’s newest Molnupiravir study (Bernal et al., NEJM), published in NEJM, contains fabricated data about coronavirus clearance (Appendix, Table S6). The rates of virus clearance from day 10 to 29 are too similar between the Molnupiravir and Placebo arms. The differences are too small compared with the large standard deviations. The standard deviations are too similar, too. This data manipulation shows that the virus clearance in the Molnupiravir arm was slower than in the placebo arm.

This is consistent with the analysis of earlier Merck’s Molnupiravir studies. Patients who started Molnupiravir earlier had worse outcomes than those who started treatment later – exactly the opposite of what one expects from an antiviral treatment. Part 2 of Phase 3 MOVe-OUT trial shows overall worse outcomes for Molnupiravir patients. Part 1 of that trial has serious integrity issues, and the placebo group’s death rates are much higher than ever found in similar population.

Earlier Molnupiravir studies that were reported to AMDAC had more shocking results. Molnupiravir not only created dangerous and rare mutations in SAR-COV-2 RNA, but also ensured that these mutations achieved a high frequency (>5%). Without Molnupiravir treatment, SARS-COV-2 viral load remains steady or decreases after symptom onset, even if the patient gets worse. The viral phase then continues for only a few days. Even a mutation that strongly benefits the virus cannot achieve a significant frequency at this time. For example, if a mutation increases the virus fitness by 5x, at a constant viral load, it will only grow 625x over four days (approximately four generations). Even if this mutation happens 10 times, it will appear in <104 virions, ~0.01% of ~108 virions typically present in a host at peak.

However, in the Molnupiravir treatment group, 7 mutations in the spike gene were found at a frequency >5%, in two or more patients each. The only plausible explanation for this is that Molnupiravir extends the viral period and increases the viral replication during this period, in at least a substantial (~20%) fraction of patients.

Some of the mutations caused by Molnupiravir were very rare; so rare that they have not even been recorded in GISAID. One of them was G261I, which could only be created by a simultaneous change of the first two nucleotides in the codon.

Two of the most dangerous mutations also occurred in the treatment group: E484K – which eliminates the neutralizing activity of many antibodies, and P681H – which accelerates cleavage and cell entry. These two mutations took many months and millions of hosts to develop in nature but were generated and selected in only 5 days of Molnupiravir treatment.

The more we learn about Molnupiravir, the higher the global catastrophic threat can be seen. For individual patients, Molnupiravir will not only cause worse COVID-19 outcomes now, but also leukemia in the future. For the globe, Molnupiravir will breed disastrous variants, at alarming speeds.

Quote from Fm1

Results During follow-up, 269 participants developed myocarditis or myopericarditis, of whom 108 (40%) were 12-39 years old and 196 (73%) were male. Of 3 482 295 individuals vaccinated with BNT162b2 (Pfizer-BioNTech), 48 developed myocarditis or myopericarditis within 28 days from the vaccination date compared with unvaccinated individuals (adjusted hazard ratio 1.34 (95% confidence interval 0.90 to 2.00); absolute rate 1.4 per 100 000 vaccinated individuals within 28 days of vaccination (95% confidence interval 1.0 to 1.8)). Adjusted hazard ratios among female participants only and male participants only were 3.73 (1.82 to 7.65) and 0.82 (0.50 to 1.34), respectively, with corresponding absolute rates of 1.3 (0.8 to 1.9) and 1.5 (1.0 to 2.2) per 100 000 vaccinated individuals within 28 days of vaccination, respectively. The adjusted hazard ratio among 12-39 year olds was 1.48 (0.74 to 2.98) and the absolute rate was 1.6 (1.0 to 2.6) per 100 000 vaccinated individuals within 28 days of vaccination.

We know well the myocarditis rates for BNT162b side effects, and also that they are normally very mild, with complete recovery after max a few days in hospital. So this paper is not adding much info - it would be interesting to have some estimate of how many of these suffer serious disease?

The TSN summary is a bit misleading. It is a great example of why I don't like TSN - they are a news site with an agenda. But they sound as though they are scientifically competent. Then they mix up Hazard ratios with percentages to get results 1000s of times worse than is actually the case.

I talk about antivaxxer incompetence and this is an example of it. Any normal person would realise those percentages were so far from anything anyone would ever tolerate and check the mistake. And any competent person could not mis up Hazard ratios and percentages.

Looking at the HRs, anything that includes 1 is basically not proven (because 1 is no effect, and the limits represent the range that can be deduced with statistical significance. This is comparing rates with the background rate.

The absolute rates (the thing usually quoted by antivaxxers, because they don't trust/understand adjustment) show no effect - they give an indication there might be some above background effect but this is not proven.

The adjusted rates (adjusted for female and male cohorts) show a strong effect for (1.82 to 7.65) for females and no effect (0.5 to 1.34) for males. That corresponds to a lower absolute rate for females (1.3 : 100K) vs males (1.5:100K) I guess because females normally have lower rates of heart disease than males.

The adjusted rates for age cohorts are all "no proven effect".

The take home for this is that although in absolute terms fewer females than males get any disease, in relative terms there is a signal that females (but not males) are affected by the vaccine. This study has a relatively small number of people so is underpowered - hence all the "not proven" indications.

It is also different from most other studies because most people think rates are significantly higher for men. It shows how difficult it is to get accurate estimates of adjusted risk relative to background. Background rates (I remember a paper I linked ages ago - thet nice self-controlled case study one - saying this) of almost any disease vary wildly between different countries due to some combo of reporting and diagnostic variations (some countries will diagnose more readily than others).

There is better data from other sources - I'd recommend NIH which says worse things about the side effects of BNT 162b than this.

Big advantage - if you read source data it is usually competent and not likely to mix up percentages with Hazard Ratios!

[Myocarditis and pericarditis following mRNA COVID-19 vaccination. Expert opinion of the Italian Society of Cardiology] - PubMed

The coronavirus disease (COVID-19) pandemic has caused 2.69 million deaths and 122 million infections. Great efforts have been made worldwide to promptly…

pubmed.ncbi.nlm.nih.gov

Quote from JedRothwell

AGAIN you post this nonsense. Nearly every person hospitalized with COVID is not vaccinated.

Jed you live in a free masons Disney world and believe everything these guys post in "trusted" journals.

The only data I trust is from UK! And there 80% of all people in hospitals are double vaxx!

Here (Switzerland) we have between 30..50% double vaxx in hospitals:: https://www.covid19.admin.ch/de/vaccination/status

Reason:: Moderna is at least 5x better than Pfizer crap!

Quote from Fm1

Conclusions Vaccination with mRNA-1273 was associated with a significantly increased risk of myocarditis or myopericarditis in the Danish population, primarily driven by an increased risk among individuals aged 12-39 years,

The study among US soldiers is now one year back. It also found about 50 serious cases among 1 million soldiers. So nothing new in town. The soldiers did see 4 excess deaths v.s. 1 expected (In total 5)

Quote from THHuxleynew

We know well the myocarditis rates for BNT162b side effects, and also that they are normally very mild,

Once more:: There are no mild cases. They call them mild because the damage is at the lower end. But there is always damage that lasts between several months to live long. Especially among children, that still have stem cells, we expect most cases do fully recover.

But the death rate in the age group 19..39 is significantly elevated!

So you should use a more competent wording!

Good news from South Africa! We are close to top of of peak with just 10% increase to past week.

South Africa COVID - Coronavirus Statistics - Worldometer

www.worldometers.info

Within the next three day we will have the definitive answer!

ICU cases did go up very moderately by about 100..130 in total( last two weeks) for several hundred thousand cases.

Deaths did only increase by single digits despite a three week high case load of > 8'000/day .

So if we assume 1 out of 10 (1 of 7 for delta in Africa or India) cases ever makes it to PCR and hospitalization is 1/10 of Delta then the pandemic will end very rapidly!

So most likely UK will see much fewer cases than the terror trumpets like to see.

Quote from Fm1

by Leo Goldstein

Merck’s newest Molnupiravir study (Bernal et al., NEJM), published in NEJM, contains fabricated data about coronavirus clearance (Appendix, Table S6). The rates of virus clearance from day 10 to 29 are too similar between the Molnupiravir and Placebo arms. The differences are too small compared with the large standard deviations. The standard deviations are too similar, too. This data manipulation shows that the virus clearance in the Molnupiravir arm was slower than in the placebo arm.

This is consistent with the analysis of earlier Merck’s Molnupiravir studies. Patients who started Molnupiravir earlier had worse outcomes than those who started treatment later – exactly the opposite of what one expects from an antiviral treatment. Part 2 of Phase 3 MOVe-OUT trial shows overall worse outcomes for Molnupiravir patients. Part 1 of that trial has serious integrity issues, and the placebo group’s death rates are much higher than ever found in similar population.

Earlier Molnupiravir studies that were reported to AMDAC had more shocking results. Molnupiravir not only created dangerous and rare mutations in SAR-COV-2 RNA, but also ensured that these mutations achieved a high frequency (>5%). Without Molnupiravir treatment, SARS-COV-2 viral load remains steady or decreases after symptom onset, even if the patient gets worse. The viral phase then continues for only a few days. Even a mutation that strongly benefits the virus cannot achieve a significant frequency at this time. For example, if a mutation increases the virus fitness by 5x, at a constant viral load, it will only grow 625x over four days (approximately four generations). Even if this mutation happens 10 times, it will appear in <104 virions, ~0.01% of ~108 virions typically present in a host at peak.

I'm not a fan of molnupiravir - because it is mutagenic and it is difficult to be sure how much that might increase cancer risk long-term. I guess an expert assessment could compare it with X-rays etc and maybe do this - but I've not seen such an analysis. So I will defer to experts, I'd like to know that a proper safety analysis has been done. I'd want a decent survey of opinion rather than TSN alarmism (yes - that is the real FUD).

Drug companies will release their best data, and put data in the most favourable light. I think it highly unlikely, for many good reasons, they would fabricate data: at least not the large ones. They will be found out, after which no regulator would ever trust the again and also the law suits would be very very expensive.

Against this we have some work from Leo Goldstein that I have not seen repeated elsewhere. I have not noticed it being suppressed - eitehr - Leo hasd made quite an internet splash with it. It is just that no-one else has backed him up.

In this case - with an outlying messenger - were I not competent to check his work - I would look at his other (older) contributions to debate to see quite how delusional they are.

I am not competent to check his work - unless he his incompetent - I can detect obvious errors.

So I was going to leave this as "likely an outlier, seems improbable, but go on watching to collect other data".

Until I found this:

Anthony Watts has embraced a very dotty conspiracy theorist called Leonid Goldstein, now known as Leo Goldstein at WUWT. Leo used to write under the name of Ari Halperin. He's been featured here before a few times. One of these days I'll write more about him. He's seriously delusional, more so than most of Anthony's freeby writers, which explains why he features on Anthony's blog, wattsupwiththat. (Anthony has been shifting further to the nutty end of nuttery lately.)

So you don't think I'm going overboard, here is the first sentence on the home page of Leonid's blog. You can see why Anthony Watts values his input at WUWT:

"Climate alarmism is a gigantic fraud: it only survives by suppressing dissent and by spending tens of billions of dollars of public money every year on pseudo-scientific propaganda."

His blog (like everything) is archived:

archive.md

I find the subtitle even more impressive:

Human breath is not a pollution. Madness Shall Stop. Down with the climate cult!

Anyway more Leo climate silliness on the hotwhopper link (or just read his archived blog).

That makes me think that, after all, I might well be competent enough to look at Leo's scientific contribution on molnupiravir.

It is not going to be easy, because Leo argues by stating conclusions - leaving us to guess as to why he makes them:

Merck’s newest Molnupiravir study (Bernal et al., NEJM), published in NEJM, contains fabricated data about coronavirus clearance (Appendix, Table S6). The rates of virus clearance from day 10 to 29 are too similar between the Molnupiravir and Placebo arms. The differences are too small compared with the large standard deviations. The standard deviations are too similar, too. This data manipulation shows that the virus clearance in the Molnupiravir arm was slower than in the placebo arm.

This is consistent with the analysis of earlier Merck’s Molnupiravir studies. Patients who started Molnupiravir earlier had worse outcomes than those who started treatment later – exactly the opposite of what one expects from an antiviral treatment. Part 2 of Phase 3 MOVe-OUT trial shows overall worse outcomes for Molnupiravir patients. Part 1 of that trial has serious integrity issues, and the placebo group’s death rates are much higher than ever found in similar population.

So:

(1) we have viral clearance difference claimed too small, s.d. too similar, between the two arms. But without any statistical analysis to back it up.

(2) (Part 2 of trial) Patients who started molnupiravir earlier had worse outcomes than those who started later

(3) (Part 1 of the trial) placebo death rates are higher than ever found in a similar population.

Maybe we can check these assertions for ourselves?

Here is a direct link to the Appendix containing Table S6

Leo is worried about those day 29 figures.

These are supplementary data taken beyond the proper test. You can see therefore that they are a selected group. (373/549 or 362/544). Since (without further investigation) we don't know how they are selected we can't say what effect that has on the values.

In addition these are log10 titre value, so identity to 2 D.P. mean similar to within 2.3%. Leo thinks this implies fabrication - but I can't see on what basis.

Let us look (same table) at the subgroup figures:

These figures are all what you would expect, compared with the whole cohort, and they are also pretty similar.

We can also see that whatever the initial RNA titre, after 29 days all these values are very similar

From the central limit theorem with S.D = 1 and 360 samples we have S.D. = 1 / sqrt(360) = 0.05

So based on independence we reckon the chances of Day 29 figures being with 0.01 are a bit of a coincidence (say 1 in 5) but not in any way a large one, and Leo has cherry-picked these figures from very many in this supplementary Appendix so you would expect him to find such.

Point (1) does not seem right - and since Leo has made the assertion without any analysis we can discount it. I cannot see why he thinks viral clearance was slower with molnupiravir than without - but what we can see is that the difference in titre is small, except at high titres, where it gets bigger. Since it is high titres which matter in terms of hospitalisation that all makes sense. No data manipulation.

Molnupiravir — A Step toward Orally Bioavailable Therapies for Covid-19 | NEJM

Editorial from The New England Journal of Medicine — Molnupiravir — A Step toward Orally Bioavailable Therapies for Covid-19

www.nejm.org

Point (2) - I will defer to a more reputable independent analysis of the Phase 2/3 results

Jayk Bernal and colleagues now report in the Journal the results of a phase 2–3 placebo-controlled trial of molnupiravir that may begin to address this global problem. The drug was administered orally (800 mg [four tablets] twice daily for 5 days) and compared with a matching placebo.⁶ Patients with mild-to-moderate disease and at least one risk factor for progression to severe illness (including age >60 years, obesity, diabetes, or cardiovascular disease) were eligible for enrollment. The primary end point was a composite of hospitalization or death at 29 days. At the planned interim analysis, 775 patients who were infected with SARS-CoV-2 and had symptoms of no more than 5 days’ duration were enrolled; 387 patients received molnupiravir and 388 received placebo. The prespecified interim analysis was performed at approximately 50% of the planned enrollment. In the molnupiravir group, the risk of hospitalization or death was 7.3% (28 of 385 patients), as compared with 14.1% (53 of 377) in the placebo group (P=0.001); no deaths had occurred in the molnupiravir group at the time of this interim analysis. However, the final analysis of these peer-reviewed data shows a more modest effect. In the final data, 1433 infected volunteers were randomly assigned to molnupiravir (716 patients) or placebo (717 patients). A primary end-point event occurred in 48 of 709 molnupiravir recipients (6.8%) and 68 of 699 placebo recipients (9.7%), an absolute difference of approximately 3 percentage points. One death occurred in the treatment group, and nine among placebo recipients. Numerous potential reasons for the lessening of the drug effect include preexisting SARS-CoV-2 nucleocapsid antibodies and lower viral load at enrollment.

I can't see Leo's point at all - and he does not justify it so I don't see how we can go further.

My point is - TSN can post trash like this from whomever it wants - and clearly will, without filter.

The problem is that they have followers (perhaps some here?) who believe, or at least half believe, what they publish.

Ivermectin study in the city of Itajaí

(PDF) Ivermectin prophylaxis used for COVID-19 reduces COVID-19 infection and mortality rates: A 220,517-subject, populational-level retrospective citywide.

PDF | Background: Ivermectin has demonstrated different mechanisms of actions that could potentially protect from both COVID-19 infection and... | Find, read…

www.researchgate.net

Background: Ivermectin has demonstrated different mechanisms of actions that could potentially protect from both COVID-19 infection and COVID-19-related comorbidities. Based on the existing literature and safety profile of ivermectin, a citywide program of prophylactic use of ivermectin for COVID-19 was implemented in Itajai, a Southern city in Brazil in the state of Santa Catarina. The objective of this analysis is to evaluate the effects of the use of ivermectin for prevention of COVID-19 infection, risk of dying and mortality, compared to non-users. Materials and methods: This is a retrospective analysis of registry data from the medical based citywide COVID-19 prevention with ivermectin program, between July 2020 to December of 2020. The whole population of Itajaí was invited for a medical visit to compile demographic and medical parameters. In the absence of contraindications, ivermectin was offered as an optional treatment for 2 days every 15 days at a dose of 0.2mg/kg/day. Patients’ preferences and medical autonomy were preserved. Ivermectin users were compared with the comorbidity-matched population of non-users for COVID-19 by age, sex, COVID-19 infection rate, and COVID-19 mortality rate. Results in terms of mortality were adjusted for all relevant variables and Propensity Score Matching (PSM) was calculated. Results: A total of 220,517 subjects were included in the analysis; 133,051 (60.3%) ivermectin users and 87,466 (39.7%) non-users. COVID-19 infection occurred in 4,311 (3.2%) treated subjects, and 3,034 (3.5%) non-treated subjects. This evidence showed a 7% reduction in COVID-19 infection rate with use of ivermectin: COVID-19 infection rate ratio (Risk ratio (RR) of 0.93; 95% confidence interval (CI), 0.89 – 0.98; p = 0.003). A total of 62 deaths (1.4% mortality rate) occurred among users and 79 deaths (2.6% mortality rate) among non-users, showing a 48% reduction in mortality rate (RR, 0,52; 95%CI, 0.37 – 0.72; p = 0.0001). Risk of dying from COVID-19 among ivermectin users was 45% lower than non-users (RR, 0.55; 95%CI, 0.40 – 0.77; p = 0.0004). Conclusion: Prophylactic use of ivermectin showed significantly reduced COVID-19 infection rate, mortality rate and chance of dying from COVID-19 on a calculated population-level analysis, which controlled for all relevant confounding variables.

Big surge may mean we will have another lock-down by Christmas, though 'I suspect it will be delayed until New Year.

Quote from Alan Smith

https://www.london.gov.uk/pres…r-declares-major-incident

Big surge may mean we will have another lock-down by Christmas, though 'I suspect it will be delayed until New Year.

‘A sad Christmas for many’: Denmark shutting down public venues amid COVID surge

‘A sad Christmas for many’: Denmark shutting down public venues amid COVID surge

The country — which has fully vaccinated 80% of those over age 5 — currently mandates masks be worn in shops and on public transportation, a rule the government hopes to expand to schools and places of worship.

Quote from Fm1

Ivermectin study in the city of Itajaí

(PDF) Ivermectin prophylaxis used for COVID-19 reduces COVID-19 infection and mortality rates: A 220,517-subject, populational-level retrospective citywide. PDF | Background: Ivermectin has demonstrated different mechanisms of actions that could potentially protect from both COVID-19 infection and... | Find, read… http://www.researchgate.net

Background: Ivermectin has demonstrated different mechanisms of actions that could potentially protect from both COVID-19 infection and COVID-19-related comorbidities.

Flavio Cadegiani is a well known maniac:

Violations of medical ethics and human rights committed in a trial of an experimental drug touted by President Jair Bolsonaro as a cure for covid-19 were the worst in Brazil’s history, the country’s research regulator has said.1

The clinical trial of proxalutamide “disrespected almost the entire protocol” and may have contributed to the deaths of as many as 200 people, said the National Health Council (CNS), which oversees clinical research in Brazil.2

Some of those people were not adequately informed of the risks they were undertaking in the trial, and some did not know that they were taking part in one, it said.

Brazil’s attorney general is investigating the possible violations of medical ethics and human rights on the recommendation of the National Research Ethics Commission (CONEP), which forms part of the CNS.2 The trial’s principal investigator, Flavio Cadegiani, was identified in October along with 68 others by a parliamentary inquiry into Brazil’s management of the pandemic as having committed “crimes against humanity.”3

Proxalutamide is an anti-androgen that blocks the function of some male hormones. It is being tested by China’s Kintor Pharmaceuticals for prostate cancer, breast cancer, and other uses. It has not been approved for use in any country but was talked up by Bolsonaro as a treatment for covid-19. Shortly after recovering from covid-19 he asked why it had not been approved for use and promised to make it available to all of Brazil.45

To test proxalutamide’s possible use against covid-19, Cadegiani—an endocrinologist and clinical director for Applied Biology—oversaw its prescription to a man exhibiting severe covid-19 symptoms. The report, which stated that after 24 hours the patient showed “marked improvement of symptoms and markers of disease severity,” was published in BMJ Case Reports on 26 February 2021.6

In February 2021 Cadegiani oversaw the drug’s administration to 645 patients with covid-19 at nine hospitals in Brazil’s Amazonas region as it was hit with a severe wave of infections. All patients were admitted to hospital, but none required mechanical ventilation at the start of the study. Usual care included medicines such as enoxaparin, colchicine, methylprednisolone, dexamethasone, or antibiotic therapy as necessary,7 and some were given unproven treatments such as ivermectin.8 Altogether, 317 patients received proxalutamide and 328 a placebo.

The treatment was prescribed by doctors as if it were an established medical treatment, said the CNS, although it was approved only for clinical studies. The number of people given the drug was also larger than the number approved for the trial, and they were administered through a private hospital network in the Amazon when the trial was approved in the capital, Brasilia.2

Reported results

The trial, which was reported on the preprint server medRxiv7 and not peer reviewed, found that the 14 day recovery rate was 81.4% with proxalutamide and 35.7% with placebo (recovery ratio 2.28 (95% confidence interval 1.95 to 2.66); P<0.001). At 28 days the all cause mortality rate was reported to be 11.0% with proxalutamide and 49.4% with placebo (hazard ratio 0.16 (0.11 to 0.24)).

Around 200 people died in the trial, mostly in the control group, although the CNS said that it had received different figures in different reports.

“The reported results would be a miracle—if they were true,” said Jesem Orellana, an epidemiologist who has closely followed the effects of the gamma variant of covid-19 on the Amazon region at Brazil’s leading public health institute, Fiocruz. “Everything about this trial is suspicious and anything but clinical and randomised.”

The mortality rate of 49.4% would not be high for the control group, as hospitals were collapsing under the pressure of the nascent gamma variant, Orellana added.

If the published results were true the trial should have been stopped and unblinded to ensure better treatment of the control group, said CONEP’s coordinator, Jorge Venâncio, in a statement. If they were not, “they subjected 200 people to die in research that has no scientific value at all.”2 High rates of kidney and liver failure were observed in critically ill patients in intensive care, suggesting that they had severe conditions, although the trial was approved for mild and moderate illness.

Consent

The Spanish newspaper El País reported that patients had trusted doctors to provide the best available lifesaving treatment and were not told that they were being given an experimental drug as part of a clinical trial.8 Some said that they were not followed up by the medical team.

The consent form given to patients omitted key sections that guarantee the rights of research participants and explain the trial, said the CNS. “In the entire history of the National Health Council, there has never been such disrespect for ethical standards and research participants in the country,” it said in a statement.

Unesco’s Network of Bioethics said that the trial showed the “most serious and alarming episodes of infraction of medical ethics in the history of Latin America,” before later retracting the post (but seen by The BMJ). It would not comment to The BMJ on the case owing to its politicisation.

Arthur Caplan, head of New York University’s Division of Medical Ethics, told The BMJ that if the alleged practices were true the trial would be “an ethical cesspool of violations, from consent and design to over-optimistic reporting of results and hiding deaths.” Falsified results have been dangerous during the covid-19 pandemic, Caplan said, as they have encouraged the popular use of unproven and sometimes dangerous drugs based on false claims.

Cadegiani denies having committed any violations of medical ethics or human rights. He told The BMJ that the trial was approved for a minimum of 294 patients rather than a maximum, that his team was well trained to inform patients of risks, and that the mortality rate was in keeping with that in the region at the time. He has taken legal action against the head of CONEP, Venâncio, for disclosing private information in his statement on the trial, which Venâncio denies. Political polarisation in Brazil is driving an “international movement” in opposition to proxalutamide and explains why his paper was rejected from other major science journals, he said.

The case report was made unavailable in November. An expression of concern said, “Following queries subsequently raised to BMJ, we are looking into the use of the drug prescribed in this case report (proxalutamide) and the circumstances surrounding its availability and license for use, and an expression of concern has been published online.”

The preprint of the trial hosted by medRxiv remains available.7 BMJ, one of the founders of medRxiv, said, “Preprints on medRxiv are usually only withdrawn by authors, rather than the server, which steps in if it is notified of the results of an institutional investigation, or retraction of the peer reviewed article from a journal, or a legitimate legal or privacy concern.”

Brazil’s drug regulator, Anvisa, has suspended the import and use of proxalutamide for scientific research on humans, but this does not apply to ongoing clinical studies approved by Anvisa. Proxalutamide appears to be under investigation as a possible treatment for covid-19 in a number of countries, including Brazil and the US.

Ivermectin: Much More Than You Wanted To Know

...

astralcodexten.substack.com

“Cadegiani et al: A crazy person decided to put his patients on every weird medication he could think of, and 585 subjects ended up on a combination of ivermectin, hydroxychloroquine, azithromycin, and nitazoxanide, with dutasteride and spironolactone "optionally offered" and vitamin D, vitamin C, zinc, apixaban, rivaraxoban, enoxaparin, and glucocorticoids "added according to clinical judgment". There was no control group, but the author helpfully designated some random patients in his area as a sort-of-control, and then synthetically generated a second control group based on “a precise estimative based on a thorough and structured review of articles indexed in PubMed and MEDLINE and statements by official government agencies and specific medical societies”.

Patients in the experimental group were twice as likely to recover (p < 0.0001), had negative PCR after 14 vs. 21 days, and had 0 vs. 27 hospitalizations.

Speaking of low p-values, some people did fraud-detection tests on another of Cadegiani’s COVID-19 studies and got values like p < 8.24E-11 in favor of it being fraudulent. Also in Cadegiani news: he apparently has the record for completing one of the fastest PhDs in Brazilian history (7 months), he was involved in a weird scandalwhere the Brazilian government tried to create a COVID recommendation app but it just recommended ivermectin to everybody regardless of what input it got, and he describes himself as:

Quote

…the only author of the sole book in Overtraining Syndrome, the prevailing sport-related disease among amateur and professional athletes. He is also responsible for approximately 70% of the articles published in the field in the world in the last 05 years, and reviewer for more than 90% of the manuscripts in the field.

And, he’s also studied whether ultra-high-dose antiandrogens treated COVID, and found that they did, cutting mortality by 92% . Which sounds great, except that it looks like most of this is that the control group had a shockingly high mortality rate, much higher than makes sense even in the context of severe COVID. I think the charitable explanation here is that he made this data up too. But the Brazilian Parliament seems to be going with an uncharitable explanation, seeing as they have recommended that Cadegiani be charged with crimes against humanity.

Anyway, let’s not base anything important on the results of this study, mmkay?

Possible impact of spike protein mutations on SARS-CoV-2 Omicron variant

Possible impact of spike protein mutations on SARS-CoV-2 Omicron variant

The current study not only analyses the mutations in the Omicron spike variant but classifies various combinations of spike mutations into groups.

www.news-medical.net

Even as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to circulate around the world, multiple new mutations continue to emerge. These have led to the detection of new variants, including the Alpha, Beta, and Delta variants that have been shown to be more transmissible, more capable of immune evasion, or both, compared to the ancestral variants.

At the end of November 2021, the latest new variant, called the Omicron, was reported by South Africa as a result of genome sequencing surveillance. With over 30 new mutations and markedly higher transmissibility, scientists are wondering if this could drive devastating new surges of reinfection, overcoming the immunity elicited by earlier infections or by current vaccines.

A new preprint explores the spike glycoprotein mutations in the Omicron variant, with their putative effects on the biological characteristics of the virus.

Background

The Omicron variant, B.1.1.529, was first designated a variant of concern (VOC) by the World Health Organization (WHO) based on the presence of numerous mutations, some of which are common to earlier VOCs. This meant that the Omicron variant was likely to be more infectious, cause more severe disease, escape neutralization by antibodies elicited by earlier variants or vaccines, and be more difficult to diagnose and/or treat.

The detection of the Omicron variant in South Africa occurred against a backdrop of rapidly rising cases, but further genomic sequencing studies are required to tell if this variant is driving the newest surge in infections. The earliest evidence of this variant is in a sample collected on November 9th, 2021.

The viral spike is the surface protein that mediates viral attachment to the host cell angiotensin-converting enzyme 2 (ACE2) receptor, thereby making viral entry into the host cell possible. It is therefore also the prime target of neutralizing antibodies to the virus.

The spike glycoprotein has two subunits, the S1 and S2, which mediate ACE2 attachment and membrane fusion, respectively, to accomplish viral entry into the target host cell. These two subunits require to be cleaved by a host furin enzyme and then show non-covalent interactions.

The RBD of the S1 subunit is involved in ACE2 receptor engagement, while the NTD recognizes several attachment factors. The S2 subunit contains the viral-host cell membrane fusion apparatus, which shows a large conformational change to cause fusion to occur. This allows the viral genome to enter the target cell via endocytosis, paving the way for productive infection.

The RBD is immunodominant, eliciting the majority of protective and binding antibodies to the virus. Since it also accomplishes virus-host cell receptor engagement, an RBD mutation is especially likely to affect the ability of antibodies to neutralize the spike. Such antibodies, elicited by vaccination or as the result of natural infection, are the basis of immune protection against infection.

Moreover, RBD mutations could also, conceivably, impact virus-receptor binding. These facts prompted the current study to identify the mutations and predict their effect on viral transmissibility, pathogenicity, and immune evasion. This prediction is necessarily based on what is known about the earlier identified mutations.

As the virus circulates in a large pool of susceptible individuals, some with antibodies against earlier strains as a result of prior infection or vaccination, mutations that change the shape or behavior of the spike in a manner that benefits the virus tend to be propagated.

For instance, if the mutation facilitates immune evasion or immune escape or allows more rapid infection to take place, it would be more likely to persist and become part of a new variant that may become dominant. For this reason, spike mutations have been the focus of all classification and functional studies of the variants of the virus.

The current study, available on the medRxiv* preprint server, not only analyses the mutations in the Omicron spike variant but classifies various combinations of spike mutations into groups. The Global Initiative for Sharing Avian Influenza Data (GISAID) database now contains over 300 Omicron sequences from African, European, and Asian countries, mostly from South Africa and other nearby countries.

What did the study show?

The researchers mapped the 37 spike mutations of the Omicron variant, which are present in anywhere between 60% to 100% of the sequences available so far. Of these, 29 occur in the S1 domain, comprising 11 in the N-terminal domain (NTD), 15 in the receptor-binding domain (RBD), and 3 in the C-terminal domain (CTD). Of the 15 RBD mutations, ten will be on the receptor-binding motif (RBM). In contrast, eight mutations were on the S2 domain.

Of the 37 mutations, 25 were found to be unique to this strain, while 12 are shared with the Alpha, Beta, Gamma, and Delta VOCs.

The 300-plus strains of the Omicron were classified into 60 groups, each with its own set of mutations. Group 1 and group 2 contain more than half the total number, at 170, containing all 37 mutations and 33 mutations, respectively. Group 1 contains almost 120 of these sequences, and Group 2 about 50.

The remaining ~140 sequences were classified into the remaining 60 groups. The presence of so many groups shows the multiplicity of mutational subtypes of this variant.

Phylogenetically, a new cluster of the Omicron variant, comprising 155 strains, emerged from the GR, Pango B.1.1 or 20B clade of SARS-CoV-2. This cluster is further subdivided into smaller clusters by spike mutation type.

What are the implications?

The presence of 37 mutations in the spike protein, especially affecting the crucial NTD and RBD portions of the S1 subunit of the protein, has raised concerns about a new wave of infections. The 12 overlapping mutations have been shown to cause higher transmissibility, higher binding affinity, or immune evasion. Scientists have predicted that the Omicron variant will continue to show these characteristics. The other 25 unique mutations are still unknown concerning their biological impacts.

The 4 RBD mutations K417N, K477N, T478K, and E484A, have been shown to confer immune evasion capabilities.

Both T478K and E484A affect residues at the immunodominant site of the RBD. The E484K mutation emerges in patients who receive monoclonal antibody or convalescent plasma therapy and confers immune escape capability. Other mutations at this site, such as E484A, E484D, and E484G, also resist antibody-mediated neutralization, while E484Q reduces the titer of serum neutralizing antibodies.

The K477N mutation enables the variant to resist neutralization by monoclonal antibodies but not convalescent plasma. The K417N, previously identified in the Beta and Delta plus variants, makes them partially resistant to neutralization by therapeutic monoclonal antibodies raised against earlier variants.

The fact that these three immune escape mutations are found in the Omicron variant may lead to a heightened potential for immune escape.

The NTD is also immunogenic and contains an antigenic supersite comprising the N-terminal end, a β-hairpin, and loop residues. The Omicron variant contains four mutations within the β-hairpin region, which may enhance immune evasion by this variant.

Four of the 11 mutations in the Omicron RBD, namely, G339D, N440K, T478K, and N501Y, were shown in a recent study to increase ACE2 binding affinity, and the other 11 reduced it.

The most important among these are Q493, Q498, and N501, because they form contact networks including hotspot residues (K31 and K353) on the ACE2 contact surface. If these are replaced by nonpolar amino acids, RBD-ACE2 binding affinity increases. Conversely, replacing glutamine at positions 493 and 498 by the more polar residue arginine may reduce binding affinity.

Thus, the magnitude of interactions between these 11 and 4 mutations with opposing effects will determine the ultimate effect on the receptor binding affinity of the Omicron variant. Meanwhile, the presence of D614G and P681H mutations that mediated high transmissibility in earlier variants means that the Omicron is expected to be highly infectious.

At present, the Delta continues to spread rapidly in susceptible communities and regions, while significant levels of vaccine-induced and natural immunity also exist. Even so, the Omicron variant is causing rapid rises in the number of infections. This seems to suggest that this strain is both highly transmissible and able to cause breakthrough infections.

If the current trend continues, omicron will supplant delta as the most common variation in South Africa and other part of the world very rapidly and may lead to another wave of COVID-19.”

*Important notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Journal reference:

Sarkar, R. et al. (2021). S glycoprotein diversity of the Omicron Variant. medRxiv preprint. doi: https://doi.org/10.1101/2021.12.04.21267284. https://www.medrxiv.org/conten…101/2021.12.04.21267284v1

Quote from Alan Smith

https://www.london.gov.uk/pres…r-declares-major-incident

Big surge may mean we will have another lock-down by Christmas, though 'I suspect it will be delayed until New Year.

Basically, because it would look bad for Boris to stop Christmas parties this year after having broken rules himself on having Christnqas parties last year (when it was not allowed), we will most likely have lockdown after Christmas when:

(1) COVID will be at higher levels, more stress on health service

(2) effect on economy etc will be larger because COVID rates get so high - everyone stays at home anyway.

(3) Boris is politically and personally so weak that he will only take action when it is absolutely certain it is needed - which is typically 2 weeks later than when action should have been taken.

I'm not sure there will therefore be more deaths overall - on grounds that nothing can stop omicron and therefore locking down earlier is just flattening a peak a bit more. However, flattening peaks maybe reduces deaths because fewer people are left without treatment.

WARNING: politics

From which you can tell that along with most in the UK I view Boris's leadership ability as close to zero. He is a "good times" leader promising honey and cake but too incompetent to deliver either unless they are already in the larder. A good leader for times when nothing needs to be done.

Quote from Fm1

Prophylactic use of ivermectin showed significantly reduced COVID-19 infection rate, mortality rate and chance of dying from COVID-19 on a calculated population-level analysis, which controlled for all relevant confounding variables.

Unluckily no zinc has been given, also V-D3 is missing. A 2 weeks regime is also far from optimal. Better is to take it once a week. So this is a pretty low end study that nevertheless shows some significant benefit.

Quote from Alan Smith

Big surge may mean we will have another lock-down by Christmas,

Terror again? Despite about 100x less patient days with Omicron? In RSA hospital load did already decline !!