Covid-19 News

    A synthetic defective interfering SARS-CoV-2


    A synthetic defective interfering SARS-CoV-2
    peerj.com


    Abstract

    Viruses thrive by exploiting the cells they infect, but in order to replicate and infect other cells they must produce viral proteins. As a result, viruses are also susceptible to exploitation by defective versions of themselves that do not produce such proteins. A defective viral genome with deletions in protein-coding genes could still replicate in cells coinfected with full-length viruses. Such a defective genome could even replicate faster due to its shorter size, interfering with the replication of the virus. We have created a synthetic defective interfering version of SARS-CoV-2, the virus causing the Covid-19 pandemic, assembling parts of the viral genome that do not code for any functional protein but enable the genome to be replicated and packaged. This synthetic defective genome replicates three times faster than SARS-CoV-2 in coinfected cells, and interferes with it, reducing the viral load of infected cells by half in 24 hours. The synthetic genome is transmitted as efficiently as the full-length genome, suggesting the location of the putative packaging signal of SARS-CoV-2. A version of such a synthetic construct could be used as a self-promoting antiviral therapy: by enabling replication of the synthetic genome, the virus would promote its own demise.


    Discussion

    DI particles have long been known to virologists (Gard et al., 1952; Huang & Baltimore, 1970) and their use in unravelling the location of functional elements of a genome is well known. Our synthetic DIs suggest that a disputed (Masters, 2019) putative packaging sequence of SARS-CoV-2 could indeed enable packaging of our synthetic defective genome –and therefore presumably acts as a packaging signal for the WT genome. However, because the difference between our DI1 and DI0 synthetic constructs is not limited to the portion with the putative packaging signal (part of nsp15), we cannot rule out that packaging signals reside in the other parts of the DI1 genome that DI0 lacks, most notably a conserved region (28554–28569) with a SL5 motifs in the N partial sequence included in the DI1 genome but not in the DI0 genome. It is also possible that DI0 can be packaged but because it does not replicate efficiently, it is rapidly degraded after transfection and the amount of packaging does not meet the threshold for detection.


    The interference with the WT virus is the most remarkable effect of our DI1 construct. As we have shown, while DI0 does not interfere significantly with WT, DI1 induces a reduction of about 50% in the amount of WT virus in coinfections compared to infections with WT alone, and this is likely due to the faster replication of the DI1 genome. DI particles are often described as by-products of inaccurate replication or as having a regulatory function for a viral quasi-species. However, DIs can also be seen as defectors in the sense of evolutionary game theory (Szathmáry, 1994; Turner & Chao, 1999, Brown, 2001): ultra-selfish replicators, able to freeride as parasites of the full-length genome. As such, DI particles need not serve any purpose for the WT virus.


    Indeed, DIs could be used as antivirals: by virtue of their faster replication in cells coinfected with the WT virus, DI genomes can interfere with the virus. Potentially, as the DI genomes increase in frequency among the virus particles pool, the process becomes more and more effective, until the decline in the amount of WT virus leads to the demise of both virus and DI. A similar therapeutic approach has been proposed for bacteria (Brown et al., 2009) and cancer (Archetti, 2013). The potential of DIs as antivirals has been suggested before (Marriott & Dimmock, 2010; Dimmock & Easton, 2014; Vignuzzi & López, 2019), and a synthetic DI particle could perhaps be immune to the evolution of resistance (although coevolution of viruses and DIs has been shown in Rhabdoviridae (Horodyski, Nichol & Spindler, 1983). Unlike, for example, HIV and influenza, which are perhaps not ideal candidates because of their short genome, multiple genomic fragments and complex replication process, coronaviruses may be more amenable to DI therapy because of their long single fragment genome and relatively simple life cycles. While the immediate 50% reduction in virus load we observed is arguably not enough for therapeutic purposes, efficacy would compound over time (as the DIs increase in frequency) and a higher initial efficacy could be obtained using a delivery vector and an improved version of the DI genome.


    Conclusions

    We have established a proof of principle that a synthetic defective interfering SARS-CoV-2 can replicate in cells infected with the virus and interfere with its replication. Further experiments are needed to verify the potential of SARS-CoV-2 DIs as antivirals. Our experiments should be repeated in human lung cell lines, against other variants of SARS-CoV-2 and by transfecting DI RNA after infection, a more realistic simulation of therapy, which will, however, ultimately require in vivo experiments. An efficient delivery method should be devised to increase the initial amount of DI RNA and to deliver it in vivo. It would also be interesting to measure how the fraction of DI and WT genomes changes over time to test whether the DI genome drives the WT genome to extinction, or they coexist at a mixed equilibrium. Finally, it would be useful to analyse the long-term evolution of coinfections to test how SARS-CoV-2 and its DIs coevolve and whether resistant mutants can arise

    The CDC Only Tracks a Fraction of Breakthrough COVID-19 Infections, Even as Cases Surge

    A May 1 decision by the CDC to only track breakthrough infections that lead to hospitalization or death has left the nation with a muddled understanding of COVID-19's impact on the vaccinated.


    The CDC Only Tracks a Fraction of Breakthrough COVID-19 Infections, Even as Cases Surge


    Meggan Ingram was fully vaccinated when she tested positive for COVID-19 early this month. The 37-year-old’s fever had spiked to 103 and her breath was coming in ragged bursts when an ambulance rushed her to an emergency room in Pasco, Washington, on Aug. 10. For three hours she was given oxygen and intravenous steroids, but she was ultimately sent home without being admitted.


    Seven people in her house have now tested positive. Five were fully vaccinated and two of the children are too young to get a vaccine.

    As the pandemic enters a critical new phase, public health authorities continue to lack data on crucial questions, just as they did when COVID-19 first tore through the United States in the spring of 2020. Today there remains no full understanding on how the aggressively contagious delta variant spreads among the nearly 200 million partially or fully vaccinated Americans like Ingram, or on how many are getting sick.


    The nation is flying blind yet again, critics say, because on May 1 of this year — as the new variant found a foothold in the U.S. — the Centers for Disease Control and Prevention mostly stopped tracking COVID-19 in vaccinated people, also known as breakthrough cases, unless the illness was severe enough to cause hospitalization or death.



    Individual states now set their own criteria for collecting data on breakthrough cases, resulting in a muddled grasp of COVID-19’s impact, leaving experts in the dark as to the true number of infections among the vaccinated, whether or not vaccinated people can develop long-haul illness, and the risks to unvaccinated children as they return to school.


    “It’s like saying we don’t count,” said Ingram after learning of the CDC’s policy change. COVID-19 roared through her household, yet it is unlikely any of those cases will show up in federal data because no one died or was admitted to a hospital.


    The CDC told ProPublica in an email that it continues to study breakthrough cases, just in a different way. “This shift will help maximize the quality of the data collected on cases of greatest clinical and public health importance,” the email said.


    In addition to the hospitalization and death information, the CDC is working with Emerging Infections Program sites in 10 states to study breakthrough cases, including some mild and asymptomatic ones, the agency’s email said.


    Under pressure from some health experts, the CDC announced Wednesday that it will create a new outbreak analysis and forecast center, tapping experts in the private sector and public health to guide it to better predict how diseases spread and to act quickly during an outbreak.


    Tracking only some data and not releasing it sooner or more fully, critics say, leaves a gaping hole in the nation’s understanding of the disease at a time when it most needs information.


    “They are missing a large portion of the infected,” said Dr. Randall Olsen, medical director of molecular diagnostics at Houston Methodist Hospital in Texas. “If you’re limiting yourself to a small subpopulation with only hospitalizations and deaths, you risk a biased viewpoint.”



    On Wednesday, the CDC released a trio of reports that found that while the vaccine remained effective at keeping vaccinated people out of the hospital, the overall protection appears to be waning over time, especially against the delta variant.


    Among nursing home residents, one of the studies showed vaccine effectiveness dropped from 74.7% in the spring to just 53.1% by midsummer. Similarly, another report found that the overall effectiveness among vaccinated New York adults dropped from 91.7% to just under 80% between May and July.


    The new findings prompted the Biden administration to announce on Wednesday that people who got a Moderna or Pfizer vaccine will be offered a booster shot eight months after their second dose. The program is scheduled to begin the week of Sept. 20 but needs approval from the Food and Drug Administration and a CDC advisory committee.


    This latest development is seen by some as another example of shifting public health messaging and backpedaling that has accompanied every phase of the pandemic for 19 months through two administrations. A little more than a month ago, the CDC and the FDA released a joint statement saying that those who have been fully vaccinated “do not need a booster shot at this time.”


    The vaccine rollout late last year came with cautious optimism. No vaccine is 100% percent effective against transmission, health officials warned, but the three authorized vaccines proved exceedingly effective against the original COVID-19 strain. The CDC reported a breakthrough infection rate of 0.01% for the months between January and the end of April, although it acknowledged it could be an undercount.


    As summer neared, the White House signaled it was time for the vaccinated to celebrate and resume their pre-pandemic lives.


    Trouble, though, was looming. Outbreaks of a new, highly contagious variant swept India in the spring and soon began to appear in other nations. It was only a matter of time before it struck here, too.


    “The world changed,” said Dr. Eric Topol, director of the Scripps Research Translational Institute, “when delta invaded.”


    The current crush of U.S. cases — well over 100,000 per day — has hit the unvaccinated by far the hardest, leaving them at greater risk of serious illness or death. The delta variant is considered at least two or three times more infectious than the original strain of the coronavirus. For months much of the focus by health officials and the White House has been on convincing the resistant to get vaccinated, an effort that has so far produced mixed results.


    Yet as spring turned to summer, scattered reports surfaced of clusters of vaccinated people testing positive for the coronavirus. In May, eight vaccinated members of the New York Yankees tested positive. In June, 11 employees of a Las Vegas hospital became infected, eight of whom were fully vaccinated. And then 469 people who visited the Provincetown, Massachusetts, area between July 3 and July 17 became infected even though 74% of them were fully vaccinated, according to the CDC’s Morbidity and Mortality Weekly Report.


    While the vast majority of those cases were relatively mild, the Massachusetts outbreak contributed to the CDC reversing itself on July 27 and recommending that even vaccinated people wear masks indoors — 11 weeks after it had told them they could jettison the protection.



    And as the new CDC data showed, vaccines continue to effectively shield vaccinated people against the worst outcomes. But those who get the virus are, in fact, often miserably sick and may chafe at the notion that their cases are not being fully counted.


    “The vaccinated are not as protected as they think,” said Topol, “They are still in jeopardy.”


    The CDC tracked all breakthrough cases until the end of April, then abruptly stopped without making a formal announcement. A reference to the policy switch appeared on the agency’s website in May about halfway down the homepage.


    “I was shocked,” said Dr. Leana Wen, a physician and visiting professor of health policy and management at George Washington University. “I have yet to hear a coherent explanation of why they stopped tracking this information.”


    The CDC said in an emailed statement to ProPublica that it decided to focus on the most serious cases because officials believed more targeted data collection would better inform “response research, decisions, and policy.”


    Sen. Edward Markey, D-Mass., became alarmed after the Provincetown outbreak and wrote to CDC director Dr. Rochelle Walensky on July 22, questioning the decision to limit investigation of breakthrough cases. He asked what type of data was being compiled and how it would be shared publicly.


    “The American public must be informed of the continued risk posed by COVID-19 and variants, and public health and medical officials, as well as health care providers, must have robust data and information to guide their decisions on public health measures,” the letter said.


    Markey asked the agency to respond by Aug. 12. So far the senator has received no reply, and the CDC did not answer ProPublica’s question about it.


    When the CDC halted its tracking of all but the most severe cases, local and state health departments were left to make up their own rules.


    There is now little consistency from state to state or even county to county on what information is gathered about breakthrough cases, how often it is publicly shared, or if it is shared at all.



    “We’ve had a patchwork of information between states since the beginning of the pandemic,” said Jen Kates, senior vice president and director of global health and HIV policy at Kaiser Family Foundation.


    She is co-author of a July 30 study that found breakthrough cases across the U.S. remained rare, especially those leading to hospitalization or death. However, the study acknowledged that information was limited because state reporting was spotty. Only half the states provide some data on COVID-19 illnesses in vaccinated people.


    “There is no single, public repository for data by state or data on breakthrough infections, since the CDC stopped monitoring them,” the report said.


    In Texas, where COVID-19 cases are skyrocketing, a state Health and Human Services Commission spokesperson told ProPublica in an email the state agency was “collecting COVID-19 vaccine breakthrough cases of heightened public health interest that result in hospitalization or fatality only.”


    Other breakthrough case information is not tracked by the state, so it is unclear how often breakthroughs occur or how widely cases are spreading among the vaccinated. And while Texas reports breakthrough deaths and hospitalizations to the CDC, the information is not included on the state’s public dashboard.


    “We will be making some additions to what we are posting, and these data could be included in the future,” the spokesperson said.


    South Carolina, on the other hand, makes public its breakthrough numbers on hospitalizations and deaths. Milder breakthrough cases may be included in the state’s overall COVID-19 numbers but they are not labeled as such, said Jane Kelly, an epidemiologist at the South Carolina Department of Health and Environmental Control.


    “We agree with the CDC,” she said, “there’s no need to spend public health resources investigating every asymptomatic or mild infection.”


    In Utah, state health officials take a different view. “From the beginning of the pandemic we have been committed to being transparent with our data reporting and … the decision to include breakthrough case data on our website is consistent with that approach,” said Tom Hudachko, director of communications for the Utah Department of Health.


    Some county-level officials said they track as many breakthrough cases as possible even if their state and the CDC does not.


    For instance, in Clark County, Nevada, home of Las Vegas, the public health website reported that as of last week there were 225 hospitalized breakthrough cases but 4,377 vaccinated people overall who have tested positive for the coronavirus.



    That means that less than 5% of reported breakthrough cases resulted in hospitalization. “The Southern Nevada Health District tracks the total number of fully vaccinated individuals who test positive for COVID-19 and it is a method to provide a fuller picture of what is occurring in our community,” said Stephanie Bethel, a spokesperson for the health district in an email.


    Sara Schmidt, a 44-year-old elementary school teacher in Alton, Illinois, is another person who has likely fallen through the data hole.


    “I thought, ‘COVID is over and I’m going to Disney World,’” she said. She planned a five-day trip for the end of July with her parents. Not only had she been fully vaccinated, receiving her second shot in March, she is also sure she had COVID-19 in the summer of 2020. Back then she had all the symptoms but had a hard time getting tested. When she finally did, the result came back negative, but her doctor told her to assume it was inaccurate.


    “My guard was down,” she said. She was less vigilant about wearing a mask in the Florida summer heat, assuming she was protected by the vaccination and her presumed earlier infection.


    On the July 29 plane trip home, she felt mildly sick. Within days she was “absolutely miserable.” Her coughing continued to worsen, and each time she coughed her head pounded. On Aug. 1 she tested positive. Her parents were negative.


    Now, three weeks later, she is far from fully recovered and classes are about to begin at her school. There’s a school mask mandate, but her students are too young to be vaccinated. “I’m worried I will give it to them, or I will get it for a third time,” she said.


    But it is doubtful her case will be tracked because she was never hospitalized. That infuriates her, she said, because it downplays what is happening.


    “Everyone has a right to know how many breakthrough cases there are,” she said, “I was under the impression that if I did get a breakthrough case, it would just be sniffles. They make it sound like everything is under control and it’s not.”

    I have to say I have not a clue about this - except..


    As I understand it cells that suffer viral replication inside them die. Therefore only a small proportion of the bodies cells are actually infected by any virus.


    This defective competing virus, to work, would need to infect the same cells as COVID - and I can't see a mechanism for that. Also, it would deliver somatic damage juts as the virus does, by destroying cells. However it would not interfere with the immune system so would not have the nasty COVID symptoms, also it would allow quite early clearance of itself (because of no immune system interference).


    I cannot see it being usable in the way the authors propose unless it can magically infect exactly the same cells that COVID does.


    I think bacteria and cancer are both different cases. I may however be missing something.


    THH

    Quote from RobertBryant

    . we know slightly more than bubkis, nada about the lengthy smallpox vaccination process

    which ended 50 years ago rather than the 100 years ago.

    Don't be ridiculous. We know about that in enormous detail.


    (It was 40 years ago, not 50.)


    Quote from RobertBryant

    but no one is looking back to 1920 to prophesy about vacccination

    Again, don't be ridiculous. Of course people look back to 1920 to study vaccination. But in any case, I was looking at 1920 to learn about the natural history of pandemics. There is a ton of data from that pandemic, and dozens of important books and studies. It was the worst pandemic in modern history, so of course people study it.


    It is as if you were saying no one looks back to 1918 to learn anything about war.

    Quote from JedRothwell

    But in any case, I was looking at 1920 to learn about the natural history of pandemics.

    ah hah I must have misunderstood you.. :)


    ,I thought ,you were saying that the vaccination process in 2021 would be as quick as the

    nonvaccination process in 1920... here


    "If enough people were vaccinated, the pandemic would end as abruptly as the 1918 influenza pandemic did."


    this is wishful thinking... but I commend it.... even though I can't really follow the logic of why

    a synthetic process in2021 should necessarily be as quick as a natural process 100 years ago for

    a totally different disease.


    however there is good news from the CDC... for us biology unsavants.

    .

    here is a simplified breakdown and a report from La France.. Vive La France


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    Quote from THHuxleynew

    Or look at a study working out age specific factors in German infection and death rates:

    You are silly don't look at fake studies. Look at the data yourself...


    Quote from zorud

    Covid-19 "Deja-vù" in Germany & Switzerland.... strong raise in hospitalizations, EC units filling again.

    Great news is the PCR+ rate of all tests that is 17.5% This tells that at least 10x more people get a free immunization.


    Germany has one hospital that does I-Maks IVR therapy, Switzerland also has one what is 10x Germany but still 99% of all Dr. Mengeles go on with no early treatment... The increase still is on a very low level.


    Quote from THHuxleynew

    Finally, the clinical study from Robert Young who has for many years claimed that ClO2 cures (everything) and sold a devoted group of adherents ClO2 on this basis.

    Poor live as a spin doctor. You have to comment every crap... Use it for gurgling - then it's OK.


    Quote from Fm1

    AZD7442 PROVENT Phase III prophylaxis trial met primary endpoint in preventing COVID-19

    $$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$ Ivermectin $

    Quote from Fm1

    As the pandemic enters a critical new phase, public health authorities continue to lack data on crucial questions, just as they did when COVID-19 first tore through the United States in the spring of 2020.

    This "public health authorities" is the wrong term. Correct Big pharma deputies in state role. It's is well known that state employees in controlling positions are former useless employees of big companies it's called bred act of grace...

    Delta in New Zealand.... the last corner of the world..vaccination rates at 20%.. total cases 81+

    NZ COVID outbreak spreads to Wellington, national lockdown extended
    The Ministry of Health has confirmed the first cases of the new wave recorded outside of Auckland.
    www.smh.com.au

    Much worse in Thailand

    These people in Thailand have taken precautions..

    Sinovac (If one can get it) versus ivermectin?

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    University of Oxford & UK-based Team Find Pfizer and Oxford Vaccines’ Effectiveness Wanes with Delta Variant


    University of Oxford & UK-based Team Find Pfizer and Oxford Vaccines’ Effectiveness Wanes with Delta Variant
    A prominent British research team led by notable researchers at the University of Oxford and other prominent British academic medical centers, government
    trialsitenews.com


    A prominent British research team led by notable researchers at the University of Oxford and other prominent British academic medical centers, government research, and the private sector, including IBM, collaborated to investigate the Delta variant and its impact on COVID-19 vaccines. Based on a large community-based survey, the team randomized households across the UK. Does the Delta variant adversely impact vaccine effectiveness? Unfortunately, yet another material data point indicates in the affirmative. More specifically, the Delta variant reduces the effectiveness of Pfizer’s BNT162b2 and the University of Oxford and AstraZeneca’s ChAd0x1 against any new Delta infections as well as those with a high viral burden.


    Interestingly and similar to a recent study finding by Mayo Clinic, one single dose of Moderna (mRNA-1273) has comparable or superior effectiveness when compared to a single dose of the Pfizer or University of Oxford/AstraZeneca vaccine. The study team further observed that “Effectiveness of two doses remains at least as great as protection afforded by prior natural infection.” The vaccine products differ markedly after the second jab as the “dynamics of immunity” between Pfizer’s BNT162b2 and Oxford’s ChAdOx1 evidence “faster declines in protection against high-level burden and symptomatic infection with BNT162b2.” Did dosing interval correlate with effectiveness? Not that the researchers could find. However, they observed that vaccinated subjects in the study experienced higher protection after a prior infection. Young adults also perform better after vaccination. Importantly, the study team observed that post two jabs, both vaccinated and unvaccinated experience comparable peak viral load. The team summarizes that while vaccination has given benefit, the emergence of the Delta variant changes the dynamics materially, leading to the concluding declaration that overall vaccine effectiveness and lessening of peak viral burden are unfortunately reduced with this evolved pathogen.


    The Study

    The study team evaluated and compared Pfizer (BNT162b2), Oxford (ChAdOx1), and Moderna (mRNA-1273) vaccines against new SARS-CoV-2 PCR positive tests, tapping into the Office for National Statistics COVID-19 Infection Survey. Results were based on what, in actuality, is a substantial community survey of people residing in randomly selected households across the UK where RT-PCR tests are conducted following a predetermined schedule, reported the authors.


    How did they measure overall vaccine effectiveness?

    By using overall RT-PCR positivity, while split based on self-reporting symptoms, cycle threshold (Ct) value according to self-reported symptoms, cycle threshold (Ct) value (<30 versus ³30) as a surrogate for viral load, from December 1 2020 (start of vaccination rollout) to May 16 2021, when Alpha dominated, and from May 17 2021 to August 1 2021 when Alpha was replaced by Delta (Figure S1; confirmed by available whole genome sequencing16). In addition, in this Delta-dominant period, we investigated variation in vaccine effectiveness by long-term health conditions, age (18-34 versus 35-65 years), the interval between first and second vaccination (><9 weeks versus ≥9 weeks), and prior infection. We also assessed viral burden in new PCR-positives occurring ³14 days after second vaccination using Ct values.><30 versus > 30 as a surrogate for viral load. This study tracked patient data from December 30, 2020, to May 2021 (Alpha dominated) and from May 17 to August 1, when Delta replaced Alpha. The investigators evaluated variation in vaccine effectiveness by several factors.


    Summary

    Full inoculation from both the Pfizer and Oxford vaccines affords material reduction of the risk associated with new PCR-positive COVID-19. While two vaccines introduce comparable benefits with the Alpha variant, the Delta reveals that the Oxford vaccine is less effective than the Pfizer vaccine. The researchers note that two doses of the Oxford vaccine maintain comparable protection to those who were previously infected and now have a natural immune system reaction. Overall, both vaccines effectiveness wanes with the Delta variant. Both Pfizer and Oxford’s vaccine waned in effectiveness by the 4th or 5th month after the second jab. The Pfizer vaccine’s effectiveness declines at a faster rate.


    Interestingly, individuals who both were vaccinated and had a previous SARS-CoV2-2 infection fare better than those who did not. The UK team could only evaluate one Modena (mRNA-1273) dose during the Delta period but observed it was more effective than Pfizer, which mirrors the Mayo Clinic study TrialSite shared recently.


    Lead Research/Investigator

    Koen B. Pouwels, Ph.D., Corresponding author.


    Follow the link to review the other authors.

    The great India vaccine terror state Kerala going with the science produces > 50% of all India cases and 1/3 of India deaths. All Ivermectin states have single digit deaths and double digit new cases.


    Even worse is the great US vaccine terror nation and the small brother Israel. USA > 1000 deaths/day

    ISR >20.


    This proves that going with the science (greed..) kills.


    RNA gen therapy is no way to end the pandemic. It's the king's way to produce more contagious virus.


    Only idiots believe that untested $$$$$$$$$$$$$$ cures better than 40 years tested $.


    Let's hold a minute's silence for all the $$$$$$$$$$$$$$$ Gilead crap (remdesivir) victims. Same for all other $$$$ therapies that never did help and all the vaccine victims that did believe they get a tested drug and never could die form CoV-19...

    How do vaccine and natural immunity compare in terms of stopping reinfection? For me, this is one of the important questions for ongoing life, along with progress in effective treatment.


    Best real world data yet (from the UK of course...). Source preprint (Oxford University - UK ONS data survey)


    expert reaction to preprint looking at the impact of the delta variant on vaccine effectiveness | Science Media Centre


    Prof Paul Hunter, Professor in Medicine, The Norwich School of Medicine, University of East Anglia, said:

    “The study by Pouwels and colleagues is a very important contribution to our understanding of the relative effectiveness of the main vaccines in use in the UK and its comparison with the protective effect of a natural infection. Unlike most earlier studies this one looked at infections in a random sample of individuals rather than rely on people presenting for testing. As such it is likely to be less biased than these other studies. One previous study that has done this the REACT-1 study in its Round 13 https://spiral.imperial.ac.uk/…_final_preprint_final.pdf, but this did not compare the different vaccine types nor did it report on the protective effects of a natural infection. There is a wealth of information in the study by Pouwels and colleagues but for me the most important findings are

    1. All three vaccines currently in use in the UK are effective at reducing the risk of infection and the risk of symptomatic infection even from the Delta variant, especially after the second dose. It does look like AZ is less effective than Pfizer, though the long term difference is a bit more complex as the initial high effectiveness of Pfizer seems to diminish more quickly which is not what would have been expected https://pubmed-ncbi-nlm-nih-gov.uea.idm.oclc.org/34002089/. Interestingly Moderna vaccine seems to be more effective against Delta after a single dose than either Pfizer or AZ as single dose or indeed after two doses AZ.
    2. The biological reason for why the mRNA vaccines seem to be more effective than AZ at preventing infection, is not certain at least to me. But early animal trials of AZ found that the vaccine “protected six monkeys from pneumonia, but the animals’ noses harboured as much virus as did those of unvaccinated monkeys” https://www.nature.com/articles/d41586-020-01092-3 & https://doi.org/10.1101/2020.05.13.093195 unlike the mRNA vaccines which did reduce nasal shedding so the finding is perhaps not that surprising. I have previously discussed the difference between systemic and mucosal immunity and how https://theconversation.com/co…symptoms-heres-why-156611 vaccines administered systemically (by infection into the arm) may not be so good at mucosal infections. One possibility is that the AV vaccine uses the same vector for both first and second dose unlike the Russian sputnik vaccine which uses to different vectors (rad26-s+rad5-s) . The Sputnik vaccine does seem to have higher efficacy https://pubmed-ncbi-nlm-nih-gov.uea.idm.oclc.org/34002089/ and it is possible that the reduced effectiveness of AZ is because of immunity against the adenoviral vector for the second dose reducing delivery https://www-sciencedirect-com.…cle/pii/S1525001604013425. However this hypothesis remains to be tested.
    3. The protective effect of a single natural infection is roughly similar to two dose immunization, with Pfizer being slightly more effective and AZ being less. However, given the fact that many people with a previous natural infection will have had their infection quite a while ago, the apparent slightly lower effectiveness against delta for natural infection is likely to be an artifact.
    4. The paper does show that immunization after a natural infection offers quite a bit greater protection than immunization alone or presumably natural infection alone. Although not included in the paper it is likely that natural infection after previous immunization will also offer rather greater protection. We are already seeing cases of infection even after double doses and these are likely to rise over coming months.

    “The main caveat to this paper is that it is in effect measuring vaccine effectiveness against asymptomatic or mildly symptomatic infection. There is now quite a lot of evidence that all vaccines are much better at reducing the risk of severe disease than they are at reducing the risk from infection. We now know that vaccination will not stop infection and transmission, although they do reduce the risk. The main value of immunization is in reducing the risk of severe disease and death and the evidence available shows that protection lasts longer against severe disease than against mild disease and all current UK vaccines are very good at this even against the Delta variant. To me that is the most important value of immunizations.”


    Prof Sheila Bird, Formerly Programme Leader, MRC Biostatistics Unit, University of Cambridge, said:

    “The ONS Infection Survey team has produced important evidence on vaccine effectiveness and cycle-threshold-value distribution (ct-value as proxy for viral load) for new positives in the Delta era.

    “Although ONS Infection Survey’s incentivized response-rate is low (less than 20%), cardinal strengths that the authors rightly highlight include: a) survey-visits are routinely-scheduled, independently of symptoms, b) ONS Infection Survey has cross-checked self-reported immunization-status against England’s Immunization Management System to good effect, c) careful definition of positive-episode (duration of up to 120 days) and d) robust standard errors to account for multiple visits per participant.

    “Eligible participants were aged 18+ years; but the vast majority of those aged 65+ years were already doubly-vaccinated by 16-May 2021 and relatively few remained unvaccinated. During the Delta era, which was defined as 17 May to 1 August 2021, some 359,000 participants {in 213,825 households} contributed nearly 812,000 study-visits and 3,123 first PCR-positives were identified. Secondary analyses therefore focus on those aged 18-64 years during the Delta era, who contributed some 297,000 study-visits (Table S1) but their number of first PCR-positives is surprisingly difficult to locate!

    “Key messages from this secondary analysis are that double-vaccinated (+ at least 14 days) vaccine effectiveness (VE) against Delta-era infection was 82% (95% CI: 79% to 85%) for BNT162B2 {Pfizer-BioNTech} versus 67% (95% CI: 67% to 71%) for ChAdOx1 {Oxford-AstraZeneca}; and against Delta-era infection with ct-value less than 30 was 86% (95% CI: 84%-88%) versus 69% (95% CI: 65%-73%). The significantly higher VE for BNT162B2 against Delta is close to the order of magnitude (20 percentage points) that the NIHR’s cancelled research-call for randomized comparison of dose-intervals had determined as policy-relevant.

    “The ONS Infection Survey team has addressed dose-interval but the chosen cut-point was less than 9 weeks between 1st and 2nd dose whereas the dose-interval in randomized controlled trials of the MRNA vaccines (Pfizer-BioNTech and Moderna) was 3 or 4 weeks. A further complication is UK’s policy-shift on dose-interval (from 12 to 8 weeks) which occurred around the start of the authors’ definition of Delta-era.

    “Cycle-threshold value, as analysed by the authors, is the lowest ct-value registered within a positive-episode (which may comprise several visits) and so, if anything, is nudged down to the ct-value that might be observed shortly before a person develops symptoms. The authors’ Figures 3B and 3C show the ct-value distribution for doubly-vaccinated new positive episodes, most of which occur in the Delta-era: reading off Figure 3C, there were of the order of 9,000 ct-values less than 30 but only around 3,000 would have been less than 18.3 (an extreme definition of “infectiousness” that has been promoted in support of INNOVA lateral flow tests) whereas only around 2,000 exceeded 25 (alternative cut-point for infectiousness that Liverpool mass screening interim report adopted).

    “Importantly, the current analysis has also investigated (Table S4) within its double-vaccinated low ct-value PCR-positive sub-population how vaccine-type (PfizerBioNTech versus OxfordAstrazeneca) influenced ct-value mean: BNT162b2-escape ct-values were initially higher by 4.0 on average (95% CI: 1.5 to 6.6) but this advantage reduced (modelled as linear reduction) by 1.6 (95% CI: 0.6 to 2.5) per 30-days since double-protection was established. Further investigation along these pioneering lines should be undertaken – as a public health priority and without prevarication – within the mass of ct-values held by NHS Test & Trace for PCR-positives in the Delta-era. These data are linkable to Immunization Management Service to establish vaccine-type and dates. Although Pillar 2 PCR-testing is not independent of symptoms, it is surely worth putting into the public domain the intelligence that can be gleaned from NHS Test & Trace.

    “Indeed, it is critical to do so as ONS Infection Survey team warn in their Discussion (p8) that “peak viral load now appears similar in infected vaccinated and uninfected vaccinated individuals, with potential implications for onward transmission risk . . . Nevertheless, there may be implications for any policies that assume a low risk of onward transmission from vaccinated individuals (eg relating to self-isolation, travel), despite vaccines both still protecting against infection, thereby reducing transmission overall.”

    “Since England’s change of policy this week on self-isolation comes within the above caution, I look to NHS Test & Trace to monitor the impact of the policy-change by putting its pertinent analyses into the public domain before August is out. This important paper gives a template to work from.”

    https://www.medrxiv.org/content/10.1101/2021.07.28.21261295v1.full.pdf


    Again, we are beginning to get delta-specific preprints with useful analysis of data. the previous preprint did not look at effectiveness against serious illness.


    This one does.


    take-home odds ratio 0.07. Unvaccinated are 14X more likely to end up needing oxygen in hospital than when vaccinated with mRNA vaccine.


    caveat - both vaccine and natural immunity effectiveness decreases over time.


    ----------------------------------------------------------------------------------------------------------------------------------------------------


    And also, on the prospects for better future vaccines (very hopeful).


    Decades-old SARS virus infection triggers potent response to COVID vaccines
    Dramatic antibody production in people infected during the 2002–04 outbreak furthers hopes of a vaccine against many coronaviruses.
    www.nature.com


    For me, the take-home is that we are still at an early phase in understanding how best to create vaccines. I actually agree with the anti-vaccine crowd in that we can do much better than the early immediate response COVID vaccines. There is therefore good hope for longer-lasting and less virus-specific future vaccines.


    So I agree that we can do much better than the very specific initial vaccines. I disagree with the highly implausible doom-laden once you have had a vaccine your immune system is screwed up forever anti-vax messaging. That has no evidence.


    There is I think much hope to be got from the response to COVID. We sure do need this hope given the certainty of future maybe worse pandemics.

    • mRNA is a great technology for quickly generating custom vaccines with minimal side-effects
    • Understanding of the immune system in great detail is getting better
    • All we need is a few future (worse) pandemics and natural selection will deal with vaccine hesitancy as a human meme - it will get selected out.

    If anyone hear adopts a Shane must be some truth to both sides approach to the W meme presented in every one of his posts, that the mRNA vaccines kill children, we could look again at the evidence?


    It is a well-known human characteristic that repeating lies causes them to be believed. I am not saying no child could ever die from a COVID vaccine. Just that a fair balance of the risks between COVID and vaccine shows that if you assume (reasonably) that all of your children will catch COVID at some time, they are less likely to die from vaccine side effects than from COVID. In addition, the uncertainties around vaccine not understood long-term side effects are an order of magnitude or more less worrisome than the uncertainties of not understood COVID long-term side effects. I'm caveating this at children 12 years or older, but with more data it is likely that will limit go down in age. I tend to be cautious about such things, so want enough regulatory authorities to have looked at all the data and come down on side of the vaccine, not just a one. The regulators like to see a lot of real-world data before acting when the overall COVID risks get low.


    Here is a how a red blooded anti-vaxxer would describe COVID - if it were a vaccine. It is all a good deal more accurate than what is said about the vaccines...


    The COVID gene therapy invades your body, replicating and causing genetic mutation in all of your cells. It subverts the immune system causing large quantities of toxic cytokines that make cells throughout the body to leak, blood clots, and strokes. Even mild infections make a permanent change to your immune system by activating some classes of cells - this has been shown to affect all organs, but particularly the brain. Likely side-effects of COVID are being suppressed by the media and the medical (choose your letters) mafia - who want us to be able to live with high rates of COVID. These include brain disorders similar to dementia and chronic fatigue, as well as heart damage. There is evidence that the brain disorders could be because blood vessels throughout the brain are known to become leaky after COVID, also that fragments of the COVID virus can pass the blood-brain barrier and live on in cells inside the brain. COVID has been shown to generate new variants each of which has been more deadly than the last one, as it learns to propagate faster and invade more of the bodies cells. We can expect this process to continue as long as there are high COVID rates in human populations. Where there is significant natural immunity new COVID variants emerge that defeat it - this is bound to happen because of natural selection. Natural immunity from COVID weakens over time - even against the same variant - and natural immunity is even less effective than vaccine-induced immunity.

    An excoriating and detailed view of the pro-ivermectin lobby evidence. Lots of good science explained here. I'm highlighting small snippets.


    Ivermectin is the new hydroxychloroquine, take 4: Bret Weinstein misrepresents meta-analyses
    [Editor's note: Dr. Gorski is on vacation this week (for the first time since the pandemic started, he's actually heading to the lake for a few days).…
    sciencebasedmedicine.org


    On combining studies and heterogeneity


    Another component not discussed by Dr. Weinstein when giving full uncritical scientific credence to the ivermectin literature, and one that undermines his point that meta-analysis the de facto gold standard information, is statistical heterogeneity. It is also a component not discussed in previous SBM posts on this meta-analysis, which makes this a good time to bring it up. When analyzing the results of a meta-analysis it is imperative to focus on the degree of statistical heterogeneity to determine if the resultant point estimate of the compiled studies are, in fact, similar enough to be combined into a singular parsimonious estimate of effect. Theoretically, multiple smaller studies can be pooled and analyzed as a singular body of evidence if the component studies are of analogous design and methodology (allocation concealment, randomization, intention to treat analysis etc.) or rejected if this is not the case. It is required that the included studies be the same in terms of design, inclusion and exclusion criteria, demographics, equivalent doses of an intervention, outcomes, and a myriad of other factors to comfortably combine said studies into a unitary body of evidence. Concordant with this is the expectation that if the included studies of a meta-analysis are of equal kind that experimentally derived results, taken under similar conditions, should roughly approximate one another. In other words, all things being equal, the same exact experiment done in multiple places by different people should roughly find the same results if the studies are in fact similar enough to be analyzed as one.


    The test to determine the heterogeneity, or the difference of the experimental results, is denoted in the arrow from the Forest plot presented above. There are several different ways to measure the heterogeneity of data but the most accessible, and understandable, measurement, is the I2 statistic that assesses the percentage of variance that is owing to heterogeneity. In general, I2is measuring the degree of variance attributable to heterogeneity with higher numbers representing more heterogeneity and lower numbers repressing a more homogenous data set. Opinions vary on the optimal percentages to categorize the impact of statistical heterogeneity but, in general, the following rules of thumb apply when determining impact of heterogeneity on the meta-analysis in question:

    • 0% to 40%: might not be important
    • 30% to 60%: may represent moderate heterogeneity
    • 50% to 90%: may represent substantial heterogeneity
    • 75% to 100%: considerable heterogeneity

    The I2 calculated for this dataset is 62%, indicating a substantial risk that the summated result provided in the “total” row derives from multiple studies that did not find the same thing and therefore is not easily reducible to a singular reliable summated estimated effect. This is an unsurprising result given the variable methodologies and definitions of the included and analyzed studies. It is possible to combine these studies and produce a single result however the combination of multiple studies does not therefore, invariably, result in reliable data.


    By way of example, it would be possible to combine multiple studies looking at aspirin for the prevention of death in myocardial infarctions into a single result and claim new knowledge under the guise of empiricism and the patina of science. However, if said studies had variable definitions of myocardial infarction, different means of follow-up, differing measures of outcomes of interest, and variable dosing regimens of aspirin, the singular discovered data point is no more a real-world reflection of the actual efficacy of aspirin than were the individual studies on their own. The combination of studies that are not the same does not get us closer to the question we are asking as the amalgamation of said studies does not, in and of itself, mitigate for the need for investigational data to be consistent with one another owing to similar experimental parameters. Such is the case with both ivermectin meta-analyses, even in their initial form with the subsequently retracted study intact, owing to the variability of the small studies included in the analysis.


    There is simply not enough evidence, at this point, to support the efficacy of ivermectin as a novel therapeutic for SARS-Cov-2 infection and certainly zero evidence for the striking claims made by Dr. Weinstein. The low-quality studies that comprise the scientific literature demonstrate that the hypothesis that ivermectin is associated with a reduction in mortality and/or transmission may be true, but the negation of this hypothesis, on a Bayesian analysis of in vitro data and the current total body of evidence, is even more likely. A mundane reading of the evidence implies, like many therapeutics before, that there is not enough evidence in either direction suggesting the need for well-done randomized controlled trials. Many other promising therapeutics have gone through similar iterations in terms of early promise in small studies followed by confirmation or rejection in larger well-designed trials. The distinction, in the case of ivermectin, is its attachment to an individual and a movement amplified via conspiratorial reasoning and anti-vaccine sentiment.


    A scientific mind, at its best, modifies hypotheses considering empirical evidence derived from experimentation or observation and attempts to fit hypotheses to the data derived. Unscientific reasoning begins with an assumed conclusion and manipulates existing and future data to fit the foregone conclusion. This sort of thinking is known as backwards reasoning and, in its most extreme, produces a cognitive bias known as anchoring in which an individual will use a particular “anchored” conclusion to fit all subsequent data. There seems to be little in the critical appraisal of the evidence or in the subsequent retraction of the largest positive study to alter Dr. Weinstein’s foundational assumption that ivermectin is an effective therapeutic for SARS-CoV-2 infection, demonstrating his unscientific approach to the assessment of evidence.


    The striking thing to note, in the case of Dr. Weinstein, is how his reasoning shifts depending on whether ivermectin is being discussed or the mRNA COVID vaccines. Large, well-conducted mRNA trials are dismissed out of hand whereas anecdotes or wild speculation and false claims are elevated to the level of meaningful data. The role of systematic reviews and meta-analysis are overstated and misunderstood whereas false claims by misleading “experts” are passed off as evidence contradicting his earlier assertions regarding evidentiary hierarchies. In a holistic view it appears, in terms of his understanding of ivermectin, Dr. Weinstein either doesn’t know, doesn’t care, or doesn’t understand what the evidence shows – I’m not certain which is the preferred option.


    Ivermectin advocates (many of whom, albeit not all, advocated hydroxychloroquine to treat COVID-19 this time last year) have apparently learned from the experience of seeing one “miracle drug” for COVID-19 fail as more randomized clinical trials showed no evidence of efficacy. Although it is possible (albeit unlikely) that well-designed randomized clinical trials will show that ivermectin has efficacy against COVID-19, the very same thing appears happening now, over a year later, for ivermectin. Meanwhile, ivermectin advocates like Bret Weinstein are still trying to portray it as a wonder drug based on a badly flawed understanding of what meta-analysis can and cannot do.


    On ecological studies (worthless - W please note)


    Quote
    The clinical experience of IVM treatments of COVID-19 in 25 countries extends far beyond the RCT results summarized, yet incomplete tracking and lack of control data exclude most of this for evaluation. The record of nationally authorized such treatments in Peru provides a notable exception [42]. In ten states of Peru, mass IVM treatments of COVID-19 were conducted through a broadside, army-led effort, Mega-Operación Tayta (MOT), that began on different dates in each state. In these MOT states, excess deaths dropped sharply over 30 days from peak deaths by a mean of 74%, in close time conjunction with MOT start date (Figure 1B). In 14 states of Peru having locally administered IVM distributions, the mean reduction in excess deaths over 30 days from peak deaths was 53%, while in Lima, which had minimal IVM distributions during the first wave of the pandemic due to restrictive government policies there, the corresponding 30-day decrease in excess deaths was 25%.

    Reductions in excess deaths by state (absolute values) correlated with extent of IVM distribution (maximal-MOT states, moderate-local distributions, and minimal-Lima) with Kendall τb = 0.524, p<0.002, as shown in Figure 1C. Nationwide, excess deaths decreased 14-fold over four months through December 1, 2020. After a restrictive IVM treatment policy was enacted under a new Peruvian president who took office on November 17, however, deaths increased 13-fold over the two months following December 1, through February 1, 2021 (Figure 1A).

    Does this sound familiar? It’s the same sort of ecological “analysis” that an astroturf group was doing for hydroxychloroquine last year that I discussed. The methods of this study are equally awful, which is probably why this article, too, is only on a preprint server thus far, and guess what? It’s a study whose first author is David Scheim, a man with no discernable expertise in the sort of complex epidemiology that would be required to make sense of the Peruvian data, while the other author is Juan Chamie of—you guessed it!—the FLCCC. I’ll say about this study the same thing that I said about the HCQ astroturf site: This is all utter rubbish, methods, conclusion, and all, as you will see. It’s so bad that it reminds me of a study by two antivaxxers without any qualifications in epidemiology, Neil Z. Miller and Gary S. Goldman, that tried—and failed—to correlate the number of vaccines in the recommended vaccine schedules of various countries with those countries’ infant mortality rates.


    Seriously, this is some really bad stuff. Let’s just put it this way. Ecological studies of the use of a drug are pretty much worthless because it’s impossible to control adequately for other potentially confounding factors or, in the case of a pandemic, the unexpected resurgence of a virus due to new variants, such as what we are seeing in the US due to the delta variant. But COVID-19 cranks do love their “real world evidence,” don’t they?


    and also...


    Ivermectin is the new hydroxychloroquine, take 5: The Nobel Prize gambit
    As regular readers know, I was on vacation last week. In my absence, guest blogger Dr. William Paolo provided an excellent fourth installment for our…
    sciencebasedmedicine.org


    On why the Elgazzar study raised red flags even before it was shown to use false data


    I knew there was something fishy about this review when I saw this in the abstract:

    Quote
    The RCT using the highest IVM dose achieved a 92% reduction in mortality vs. controls (400 total subjects, p<0.001).

    That part about 400 subjects plus the 92% reduction in mortality is a narrative I had heard before. Hmmm, I wondered, Which study is that? It sure sounds familiar. It didn’t take me long to realize that this was a study out of Egypt (Elgazzar 2020) that (1) had never been peer reviewed and only been available on a preprint server; (2) as the largest randomized trial of ivermectin for COVID-19 drove seemingly “positive” results in meta-analyses even though the rest of the studies without it wound up producing a negative result; and (3) was very likely was fraudulent, complete with plagiarism and data that appeared to have been made up, leading to its retraction from a preprint server—surely the first time I had ever seen that before!

    Let’s just put it this way, if the results from Elgazzar 2020 reflected ivermectin’s true activity, then, as Gideon Meyerowitz-Katz (whom I have quoted before) noted in his discussion of the potential fraud, ivermectin would be “most incredibly effective treatment ever to be discovered in modern medicine”. As a physician (opposed to an epidemiologist), I did quibble a bit with Meyerowitz-Katz (we do have treatments that are greater than 90% effective at eliminating the diseases or conditions that they treat, especially a number of vaccines), I couldn’t deny that he was certainly correct if one were to restrict this observation to antiviral drugs. If Elgazzar 2020 were accurate and generalizable, ivermectin would indeed be the most incredibly effective antiviral treatment ever to be discovered. I further noted that that result alone should have raised a number of red flags. Of course, it did among authors doing meta-analyses who were not ivermectin advocates from the BIRD Group or the FLCCC, which is why they excluded it from their analyses. Apparently it did not for the authors of this review, who accept its results as basically fact, stating again in the text:

    Quote
    The RCT that used the largest dose of IVM, 400 µg/kg on each of days 1-4 [22], had 2 vs. 24 deaths in the treatment vs. control groups (n=200 each), a 92% reduction in COVID-19 mortality (p<0.001).

    Fair and balanced conclusions


    There is simply not enough evidence, at this point, to support the efficacy of ivermectin as a novel therapeutic for SARS-Cov-2 infection and certainly zero evidence for the striking claims made by Dr. Weinstein. The low-quality studies that comprise the scientific literature demonstrate that the hypothesis that ivermectin is associated with a reduction in mortality and/or transmission may be true, but the negation of this hypothesis, on a Bayesian analysis of in vitro data and the current total body of evidence, is even more likely. A mundane reading of the evidence implies, like many therapeutics before, that there is not enough evidence in either direction suggesting the need for well-done randomized controlled trials. Many other promising therapeutics have gone through similar iterations in terms of early promise in small studies followed by confirmation or rejection in larger well-designed trials. The distinction, in the case of ivermectin, is its attachment to an individual and a movement amplified via conspiratorial reasoning and anti-vaccine sentiment.


    A scientific mind, at its best, modifies hypotheses considering empirical evidence derived from experimentation or observation and attempts to fit hypotheses to the data derived. Unscientific reasoning begins with an assumed conclusion and manipulates existing and future data to fit the foregone conclusion. This sort of thinking is known as backwards reasoning and, in its most extreme, produces a cognitive bias known as anchoring in which an individual will use a particular “anchored” conclusion to fit all subsequent data. There seems to be little in the critical appraisal of the evidence or in the subsequent retraction of the largest positive study to alter Dr. Weinstein’s foundational assumption that ivermectin is an effective therapeutic for SARS-CoV-2 infection, demonstrating his unscientific approach to the assessment of evidence.


    The striking thing to note, in the case of Dr. Weinstein, is how his reasoning shifts depending on whether ivermectin is being discussed or the mRNA COVID vaccines. Large, well-conducted mRNA trials are dismissed out of hand whereas anecdotes or wild speculation and false claims are elevated to the level of meaningful data. The role of systematic reviews and meta-analysis are overstated and misunderstood whereas false claims by misleading “experts” are passed off as evidence contradicting his earlier assertions regarding evidentiary hierarchies. In a holistic view it appears, in terms of his understanding of ivermectin, Dr. Weinstein either doesn’t know, doesn’t care, or doesn’t understand what the evidence shows – I’m not certain which is the preferred option.


    Ivermectin advocates (many of whom, albeit not all, advocated hydroxychloroquine to treat COVID-19 this time last year) have apparently learned from the experience of seeing one “miracle drug” for COVID-19 fail as more randomized clinical trials showed no evidence of efficacy. Although it is possible (albeit unlikely) that well-designed randomized clinical trials will show that ivermectin has efficacy against COVID-19, the very same thing appears happening now, over a year later, for ivermectin. Meanwhile, ivermectin advocates like Bret Weinstein are still trying to portray it as a wonder drug based on a badly flawed understanding of what meta-analysis can and cannot do.



    (not from the above link)


    A Note on Medical Politics


    This is the science. It does not answer the question - how much should individual doctors be discouraged from giving patients un-evidenced treatments just because their gut feeling says this is a good idea? Certainly the medical establishment throughout history has reckoned that is exactly what doctors should do, and it is only in the 20th Century that things have changed with the rise of evidence-based medicine and a realisation that many treatments beloved of doctors do more harm than good. How tolerant should we be of quacks - on the grounds that all is uncertainty and individual doctors bravely going against the herd should be allowed? And should patients demanding something that is not evidenced on the basis of misinformation be allowed to have it when it is not likely to be very dangerous?


    These are political, not scientific questions. I don't have strong views about them because can see both sides.

    Anchoring bias in the growing number of COVID-19 vaccine breakthrough infections


    Anchoring bias in the growing number of COVID-19 vaccine breakthrough infections
    Note that views expressed in this opinion article are the writer’s personal views and not necessarily those of TrialSite. Dr. Ron Brown – Opinion
    trialsitenews.com


    Dr. Ron Brown – Opinion Editorial


    August 20, 2021


    “I was fully vaccinated, but I just tested positive for COVID-19. Without the vaccine, my condition would have been much more severe. At least the vaccine prevented me from going to the hospital and dying.” This is a typical reaction reported in the media as the number of COVID-19 vaccine breakthrough infections steadily increase. Of course, no one knows for sure what their outcome might have been without the vaccination, but that doesn’t stop people from forming assumptions based on the superior vaccine efficacy reported in the COVID-19 mRNA vaccine clinical trials. After all, considering the proven ability of the vaccines to prevent approximately 95% of infections, surely the vaccine afforded some protection—even though evidence of the breakthrough infections shows the opposite. This cognitive bias is a type of faulty thinking known as anchoring bias, in which a person continues to return to (is anchored to) the same faulty initial judgment, without adjusting to new evidence. Anchoring Bias – Biases & Heuristics | The Decision Lab.


    In this case, the faulty initial judgment stems from outcome reporting bias of the clinical trials which claimed that the COVID-19 mRNA vaccines were exceptionally efficacious. Medicina | Free Full-Text | Outcome Reporting Bias in COVID-19 mRNA Vaccine Clinical Trials (mdpi.com). Efficacy means how effective the vaccines work under controlled conditions of a randomized trial, in contrast with effectiveness in real life conditions without controls, often measured in observational studies that are prone to selection bias and have lower standards of evidence that cannot prove causation.


    Vaccine efficacy is measured in a clinical trial with a statistic called the relative risk reduction, which accounts for the approximate 95% reduced risk of healthy people developing an infection with at least one mild symptom.


    Notice that healthy people were selected for the COVID-19 vaccine clinical trials, not people with underlying health conditions or other circumstances that put them at high risk of severe infections, hospitalizations, and death. This latter group of people are the trial participants that would need to be tested to support any claims of the vaccines’ ability to prevent severe infections, hospitalizations, and deaths. But a clinical trial involving these high-risk people never happened.


    Yet, the media and public health authorities continue to spread the extraordinary claim that because otherwise healthy vaccinated people didn’t immediately die from the infection, this proves the vaccine protected them from death. I also went outside this morning for a walk, which proves that my walk prevented Earth from being invaded by extra-terrestrials (Too late, they’re already here).


    More importantly, the most serious outcome reporting bias in the clinical trials is due to the omission of reporting the vaccines’ absolute risk reduction, or its reciprocal known as the number needed to vaccinate. This risk reduction measure shows the actual reduction in infections between the vaccine and placebo groups, which is approximately 1% in the COVID-19 mRNA vaccine clinical trials.


    Absolute risk reduction provides more useful information on which to base clinical and public health decisions, whereas relative risk reduction is more often intended for use by researchers to compare studies of different trials.


    Lacking awareness of outcome reporting bias in the COVID-19 mRNA vaccine clinical trials, and obviously unaware of the ultralow absolute risk reduction to prevent even a simple mild infection, people remain anchored to their initial belief that the vaccines have extraordinary abilities to prevent severe infections, hospitalizations, and deaths. Due to anchoring bias, it never occurs to these people that their currently held belief is wrong, despite evidence to the contrary mounting before their eyes


    Outcome Reporting Bias in COVID-19 mRNA Vaccine Clinical Trials

    Outcome Reporting Bias in COVID-19 mRNA Vaccine Clinical Trials
    Relative risk reduction and absolute risk reduction measures in the evaluation of clinical trial data are poorly understood by health professionals and the…
    www.mdpi.com

    Quote from THHuxleynew

    The protective effect of a single natural infection is roughly similar to two dose immunization, with Pfizer being slightly more effective and AZ being less.

    Intellectual nonsense. If you have real data then use it. Israel data says a natural infection is at least 6.7 x better protecting you. The MA event did show nobody with a prior infection has been infected.


    So this is pro vaxxx FUD.

    Quote from THHuxleynew

    So I agree that we can do much better than the very specific initial vaccines.

    Yes we can do 1000000X better

    Quote from THHuxleynew

    mRNA is a great technology for quickly generating custom vaccines with minimal side-effects

    More provax FUD.


    Quote from THHuxleynew

    That part about 400 subjects plus the 92% reduction in mortality is a narrative I had heard before.

    This was bad wording. In Italy 9 out of 10 died on ventilators. In Egypt - at teh same time - only 2 died with Ivermectin and 20 with HCQ. Using percent figures make no sense if you have mixed (age, illness degree etc.) classes. Just show the numbers that are impressive.


    Nothing wrong with El Gazar data. Just very bad presentation...


    So please focus on real world Ivermectin data from In India that makes studies obsolete.


    Quote from Fm1

    After all, considering the proven ability of the vaccines to prevent approximately 95% of infections,

    This assumption is the cheating trick of the vaccine terror mafia. Also 95% of all unvaccinated do not go to hospital. This natural protection is claimed to be vaccine protection .... So you have always to divide that vaccine group by 20 or multiply the vaccine break through cases by 20 to get the same weight!


    In fact a very small group age >75 is the real contribution of the vaccine success. For all the others is more or less none.


    This is why a famous study could show that real vaccine protection is just 1% for death.

    Huélum! Poli scientist develops 90% effective drug against COVID-19

    The drug could start its clinical trial with patients in early 2022 with the support of the INER.


    Huélum! Poli scientist develops 90% effective drug against COVID-19


    This article was translated from our Spanish edition using AI technologies. Errors may exist due to this process.


    This morning we want to sing the iconic cheer of the National Polytechnic Institute (IPN): "Huélum, Huélum, Gloria A la Cachi Cachi Porra A la Cachi Cachi Porra Pim Pom Porra Pim Pom Porra Politécnico, Politécnico, Gloria!"


    The reason is that a drug against COVID-19 developed by the expert in virology and immunology of the National School of Biological Sciences Paola Castillo Juárez has shown an efficacy of more than 90% to treat the virus .

    According to the IPN page , the treatment was created from the design of four peptides (small protein fragments). These inhibit the replication of the virus and stop the inflammation that it generates and is related to the multisystemic damage that COVID-19 generates.

    The results are surprising because the molecules developed focus on conserved sequences of the parts of the SARS-CoV-2 protein, which do not change even when the virus mutates and gives rise to new variants," said the researcher in a statement from the Poli .

    Castillo Juárez said that it is already in the process of registering the patent for the drug and that it will begin to carry out tests to verify its effectiveness against the Delta variant.


    "Since the peptides are directed at sequences of the virus's proteins that do not change (conserved), we are completely sure that they will also be very effective against this variant," said the scientist.

    The drug must now be tested in animals by the end of 2021 to start the clinical trial with patients in early 2022 with the support of the National Institute of Respiratory Diseases (INER).

    Another Case for Mucosal Immunity as a Pathway Out of the COVID-19 Crisis


    Another Case for Mucosal Immunity as a Pathway Out of the COVID-19 Crisis
    Recently, in the Wall Street Journal (WSH), a neurologist and neuroscientist Michael Segal put it bluntly: the Centers for Disease Control and Prevention
    trialsitenews.com


    Recently, in the Wall Street Journal (WSH), a neurologist and neuroscientist Michael Segal put it bluntly: the Centers for Disease Control and Prevention (CDC) is confusing people across the country by a seemingly contractor claims “Vaccinated people are supported to resume wearing masks, lest they contract and spread the virus.” Yet unvaccinated people are still strongly urged to get the shots, which are said to be highly effective.” The physician ponders, can both of these declarations be true?


    Dr. Segal touches on a topic covered recently by TrialSite’s piece in “America’s Vaccine-Centric Strategy to Overcome SARS-CoV-2 Failing while Adequate Testing & Data Collection ‘Grossly Inadequate’.” That is, there are different kinds of immunity. The current crop of vaccines are designed to foster “Internal Immunity,” declares Dr. Segal, which is protection “inside of the body, including the lungs.” Thus, most vaccinated people avoid hospital as the vaccines are protecting them from “being overwhelmed by the coronavirus,” declares Segal. That is why the health authorities are now making this next big vaccination push, as a way to reduce the stresses and strains on the health care systems, ICUs, and the like.


    But as TrialSite shared the thinking of Dr. Eric Topol, one of the most influential physicians and researchers in the country, mucosal immunity is quite different. It offers the human subject the “first line of defense by protecting the nose and mouth,” writes Segal, thus lowering the risk of transmission to others.


    As it turns out, Topol, Segal, and undoubtedly many others have come to terms with the fact that the current vaccines “…are largely ineffective at stimulating the secretion of IgA into our noses that occurs after actual infection with a virus.” The result, of course, is what we are now witnessing around the world, a growing number of so-called breakthrough infections. This trend started unfolding in heavily vaccinated places such as Israel, where there has been a clear lowering of vaccine effectiveness over the past couple of months with the Delta variant’s rise. In fact, growing numbers of breakthrough infections in Israel lead to hospitalization, a trend not repeated by the mainstream media. A recent event at Herzog Hospital emphasizes the risks now, as reported by TrialSite.


    Government Pivots Herd Immunity Rationale

    As TrialSite has been reporting, early on, the government’s vaccine-centric strategy was to stop transmission and contribute to societal herd immunity. After all, at some point, nations around the world should reach that point. But with Delta and the rise of large numbers of breakthrough infections, that narrative didn’t reflect reality.


    Thus, the government narrative changed when scenarios emerged where the nasal viral load remains just as high in vaccinated individuals as unvaccinated. Interestingly just as this data became apparent, the Biden Administration doubled down on their vaccine-centric mission, declaring that the pandemic was now only one of the “unvaccinated.” Biden is a seasoned political operator, but we think he is taking what he thinks is the right side pragmatically and historically. However, the reality on the ground indicates we are transitioning to a new phase in this pandemic, one with different rules.


    That’s evidenced by the Mayo Clinic study TrialSite introduced to the community , which Dr. Segal also refers to in his opinion piece. As TrialSite declared in “Delta Troubles? Retrospective Study led by nference and Mayo Clinic Reveals Pfizer COVDI-19 Shot only 42% Effective during July“ it reveals the vaccines’ overall effectiveness wanes with time in combination with variants such as Delta. Pfizer’s vaccine effectiveness declined to 42%. While Dr. Segal still believes there is a slim chance for herd immunity, all sorts of rules and changes would need to occur. Politically, that may not be feasible. Segal does declare, “we shouldn’t shun people who have recovered from COVID.” Why? Because of natural mucosal immunity.


    Call to Action: Visit the WSJ and read Dr. Sega’s entire opinion piece.


    Opinion | Follow Your Nose to Herd Immunity
    The biology behind ‘breakthrough’ cases and the confusing CDC mask guidance.
    www.wsj.com

    An Argument for Masks & A Fundamental Underlying Tension Inhibits Common Grounds


    An Argument for Masks & A Fundamental Underlying Tension Inhibits Common Grounds
    The mask wars heat up in this rapidly evolving world of extremes, as one side seeks unilateral adherence to centralized public health edits (e.g., NIH,
    trialsitenews.com


    An Argument for Masks Yet A Fundamental Underlying Tension Inhibits Common Grounds



    The mask wars heat up in this rapidly evolving world of extremes, as one side seeks unilateral adherence to centralized public health edits (e.g., NIH, CDC, FDA). In contrast, the other side seeks more state and localized control over determinations of mask mandates, for example. The whole affair now heats up as the recent Florida Gov. Ron DeSantis and other Republican governors went into action attempting to block various mandates from local school districts. Of interest in the United States, schools are fundamentally governed at the local school board level, so this is an example where Republicans are probably overstepping traditional constitutional boundaries. Regardless, school districts and boards are defying Gov. DeSantis in Florida, setting up further clashes as reported in CBS 4 Miami. Will the DeSantis administration move to punish these school officials? Will the federal government under POTUS come to their defense? But what about the science of masks? TrialSite shared the pros and cons, and upon review of CDC examples (top example a couple of hairstylists), the evidence is sparse at best. Recently, Kaiser’s KHN published a piece by PolitiFact’s Louis Jacobson, which TrialSite reviews below.


    Jacobson refers to several claims and positions that masks could potentially pose harm to children but suggests “generally we found that concerns about significant negative effects on breathing aren’t well supported.” But how do they back up this claim?


    The PolitiFact writer first emphasizes that “masks aren’t recommended for everyone.” Pointing to the American Lung Association’s guidance that those with lung disease shouldn’t wear a mask unless a consultation with the doctor offers the greenlight. Moreover, don’t wear a mask during heavy workouts, declares the writer. Who could possibly be hurt by wearing a mask, Jacobson asks, and shares some common concerns:


    Lack of oxygen

    Buildup in carbon dioxide

    According to PolitiFact, these arguments are “oversold” while University of California, San Francisco medicine professor Babak Javid declares the issue “has been convincingly debunked,” writes Jacobson.


    Some Evidence for Mask Concerns?

    Jacobson points out that most mask studies involved adults and not children. He pointed to two N95-based mask studies, which are heavy-duty and wouldn’t be in schools. Involving children, the studies found “no significant effect on breathing.”


    The author notes that some authors, such as Benjamin Neuman, biology professor at Texas A&M University, suggest mask-wearing “will add some resistance to the breathing process, meaning it may feel like it takes a bit more work to take a breath, but it wont’ materially change the makeup of air that comes back through the mask.” He is the chief virologist of the Global Health Research Complex.


    Disappoint as to Lack of Child Data

    The KHN piece shared a published meta-analysis revealing that a dearth of information was disappointing to the authors, who urged for more child research on the question. But the study authors emphasized there was “little reason for worry.” They penned, “The eight adult studies…reported that face masks commonly used during the pandemic did not impair gas exchange during rest or mild exercise.”


    But what about a couple of studies indicating masked children may face breathing problems? Conveniently one such study was retracted by JAMA Pediatrics just 16 days after publication due not “methodological shortcomings and other concerns,” writes Jacobson. And Dr. David Hill, a board member with the American Lung Association, shared that masks “absolutely” do not cause low oxygen levels, as inked by Jacobson.


    The PolitiFact writer shared a quote from Babak Javid, centering on the fact that “the world has engaged in a massive study—observational, but literally billions of people—on mask-wearing, and people not dropping dead, left, right and center.”


    Jacobson acknowledges other potential sources of concern and shoots down any medical fears but acknowledges some studies could indicate psychological issues could surface. For example, in a 2020 paper in the International Journal of Environmental Research and Public Health, the authors declared, “while there are minimal physiological impacts on wearing a mask … there may be consequential psychological impacts of mask-wearing on the basic psychological needs of competence, autonomy and relatedness.” Perhaps other risks are relevant, and again, TrialSite’s review of the evidence suggests neither side has a slam dunk case.


    Divisions, Disdain & Disrespect by Both Sides

    Overall, this mandatory mask conflict during the middle of a pandemic is more about politics and control than about safety. Even when kids are wearing masks, they are notorious for taking off masks here and there, not washing their hands, picking their noses, and all sorts of other behavior that will end up with pathogens transferred to other kids, and ultimately parents.


    A seemingly political war emerges between what are two already entrenched, positioned yet antiquated sides. Transcending COVID-19 is nearly impossible to do on an accelerated timeline if society isn’t somewhat aligned around actions and recourse.


    Arguments one way or another don’t matter. It’s similar to early treatment options of a generic repurposed nature. The threshold to get them emergency use authorized seemed far higher than products like remdesivir. The NIAID changed the endpoint toward the end of the study, and the World Health Organization (WHO) has come outright based on the Solidarity trial to declare the drug has no benefit.


    In fact, some studies reveal safety issues. But Gilead went on to generate $3 billion or so in the first nine months of the pandemic regardless.


    Undoubtedly, where there is lots of money to be made, both sides get a lot chummier, at least behind the scenes. Could it be that the politicians are part of a far more dark, nefarious underlying divisive force, meant to keep the majority of people in places like America permanently divided? That certainly makes it easier for whoever is making out super well to keep doing so despite the prevailing misery index levels.


    University of Cincinnati Study Raises Questions Associated with Use of Remdesivir in COVID-19 Patients – TrialSiteNews
    Much attention was placed on the antiviral drug remdesivir during the early stages of the COVID-19 pandemic. In fact, considerable public money was allocated…
    trialsitenews.com

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