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Dontshootrude

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Posts posted by Dontshootrude

  1. 41 minutes ago, Satoshi said:

     

    Funny/CSB story.  CDC has protesters come and go, but there is one dude that is always right outside CDC rain or shine, hot or cold, with about 10 signs walking up and down the sidewalk that say things like "Infertility," "Genocide," "Obey," etc.  As crazy as he is I tip my cap to him for being so incredibly dedicated and so confident in himself that he can do that just about every day by himself. It is a shame he has latched onto something this crazy, because if he would have picked something productive no doubt he would have been highly successful. 

    Something tells me the Nicki Minaj protesters won't be so driven.  

  2. 2 hours ago, Bevo said:

    Also some articles that may be of interest:

     

    Ab response to SARS-CoV-2

    https://www.biorxiv.org/content/10.1101/2021.01.15.426911v1.full

     

    SARS-CoV-2 viral targets

    https://www.nature.com/articles/s41577-020-00480-0

     

    Just a review article on lipid encapsulation of mRNA (You would be one of the few who may be interested). A long-time ago I worked on transfection agents which is where all this derived. BTW, there is a guy in Austin who was a director for the Bay Area company that developed the lipid encapsulated Amphotericin B and daunorubicin products.

    https://www.nature.com/articles/s41578-021-00358-0

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5439223/

    That nature review on lipid delivery of mRNA was interesting  It lead me to this paper in which people got eight shots and they were continuing to develop good immune responses.  That is encouraging news and helps alleviate my concerns regarding decreasing efficacy due to the immune system recognizing the capsule!  

    As to the other papers, those were published right as we were mass deploying the vaccines.  I was more concerned then, but thankfully recent data has held up well, especially against severe disease.  I'm optimistic that will continue.

    ETA: I also found the references that highlight the diverse array of vaccine induced epitopes and how well they are holding up for the vaccines.

    https://www.biorxiv.org/content/10.1101/2021.02.27.433180v1

    https://www.sciencedirect.com/science/article/pii/S2666379121002044

  3. 1 hour ago, Bevo said:

    I'm not so sure. That article that you linked a few days ago seemed to miss some important points. While mutations from within vaccinated individuals may be lower than in unvaccinated individuals, a mix of unvaccinated individuals and vaccinated individuals will potentially lead to new strains that are more infectious and perhaps even circumvent the spike protein antibodies. I think using the spike protein only in an mRNA vaccine will prove to be a mistake and more targets should be included in the vaccine. In other words, related to the quoted part of your post, I am not confident in the long-term efficacy of the current vaccines on the market. I don't even think you are that confident as you think the lipid encapsulation of the mRNA may cause a decrease in efficacy as more boosters are given. I think this is possible as well.

    I disagree.  Truth is there are fundamental biological reasons why I think it unlikely that COVID will be able to find a mutation that will significantly escape our vaccines.  When replicating, coronaviruses, including COVID, have a proofreading mechanism (PDF warning) that will verify the genetic sequence that is being replicated. It is not as robust as that in eukaryotic cells (human, mammals for example) whence the mutations we do see, but it does exist.  Compare COVID to a true rapidly mutating virus like flu.  Flu has two mechanisms that allow it to radically mutate in short periods of time.

    1. Genetic drift - random point mutations in the genome from the highly error prone replication enzymes that lack proof reading that it uses to replicate its RNA genome

    2. Genetic shift - completely swapping out entire gene segments for new ones creating a whole new unique flu virus. Only Influenza A viruses can do this which is why they are responsible for the pandemic strains.

    To highlight this, check out the two files attached to this post.  The COVID_Variant_Alignment file are the top five variants of concern aligned against the original COVID sequence provided to CDC back in January 2020 that the vaccine was designed against. An * under the specific base means the nucleotide is the same among all six strains. Notice how much of the sequence is the same among all six, and you really must hunt to find changes. I've also attached an alignment from a surface protein of flu, a true rapidly mutating virus for comparison. Notice how inconsistent the flu is and you'll see why it is so challenging to design effective vaccines and therapeutics.

    Shifting back to the vaccines, the spike protein is a big protein.  I've seen studies that report CD8+ (T killer cells, the ones that seek out and kill infected cells) recognizes 52 epitopes (spots on the protein).  CD4+ cells (T helper cells, which help drive antibody responses) recognize 23 epitopes across the entire spike protein.  I'll try to find my references for this later, but offhand I can't recall exactly which study addressed this.  It is hard to imagine, given how stable COVID is, that it will find a way to alter all of these regions and still remain infectious.

    Comparing the Beta variant vs Delta is encouraging too.  Beta is actually more genetically distant than delta and the vaccine was less effective against it compared to delta.  But Delta has outcompeted it nonetheless.  

    This is a good article that partially addresses what I'm saying above.

    And one finally thing I should mention regarding the immune response to the lipid capsule delivery vehicle.  I wouldn't  say I'm extremely worried about this. I'd just like to see it addressed before I take a shot that decreases my risk of hospitalization from 1 in 300,000 to 1 in a couple of million.   

    COVID_Variant_Alignment.txt Influenza_H1gene_alignment.txt

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  4. Continuing our Surly literature review, I ran across a couple interesing things today.  The first is more booster data relating to younger age groups than what was published in the NEJM paper I posted yesterday.  

    Israeli_Data.thumb.png.0f2e430a40799f5bb3bddf92f9edd224.png

    This reinforces the data we have seen that in younger healthy populations the breakthrough cases are increasing but remain mild in nature.

    Also, this encouraging preprint out of the UK was posted today.

    This is of course very preliminary, but I liked the concluding statement: 

    Quote

    Although there is considerable uncertainty attached to any extrapolation into the future, the best estimate we can make on the basis of the data available is that the rapid waning of efficacy against COVID-19 in the first two months after the second dose tapers off thereafter and that the trajectory is consistent with a long-term efficacy of about 80% against hospitalisation. Thus at present there is no clear evidence to support a policy of delivering booster doses to the entire population, rather than to vulnerable individuals for focused protection.

      Given the slow mutating nature of coronaviruses I'm optimistic in the long term efficacy of our vaccines. 

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  5. 3 hours ago, NeverMarryAStripper said:

    My mom is coming up on 6 months for her Pfizer vaccine.  Has there been any discussion of switching for the booster?

    Not yet, but today was a pretty big day for publications.  Two studies were released in the New England Journal of Medicine relating to the Pfizer vaccine.

    1. A follow up study on the original 44,000+ clinical trial participants.  Those that got the vaccine are continuing to do very well.  Efficacy had wained from 95% to 83%.

    https://www.nejm.org/doi/full/10.1056/NEJMoa2110345?query=featured_home

    2. This is the big one. The Israelis just published their 3rd shot trial involving over 1 million people. It's very well designed and controlled.  In people 60 and older the third shot reduced severe disease by 19.5x, essentially bringing the vaccine efficacy back to what it was when they first received it.  They don't specifically discuss side effects, but the absence of that data is probably a good sign.  Based on this study I'm going to tell my parents to sign up for a booster.

    https://www.nejm.org/doi/full/10.1056/NEJMoa2114255

     

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  6. 3 minutes ago, Anastasis said:

     

    Things that were largely established weeks and months ago. 

    Oh I don't know about that.  I agree it has been clear that there are people that would benefit from a third shot, but at which age that benefit starts to be measurable will really be tied down with this study.  It is the first well designed and controlled study on a large number of people regarding boosters that I will have seen.  Maybe I missed a few?  Please link if so. 

  7.  

    I'll be eagerly awaiting this publication later this week.  It has been ambiguous at which age at which the third shot will make sense at this point.  From this sneak peak out of Israel it looks like the answer will be 60 years of age and those who are immunocompromised.  

  8. 5 minutes ago, Victor Lazlo said:

    I’m not the enemy. The jackasses that haven’t been infected or vaccinated are the ones that should be getting the heat.

    Yep.  Those naïve to infection, and those that think pork makes better BBQ than beef and anyone who has liquid smoke in their house should have their ass mandated into oblivion. 

  9. 16 minutes ago, Victor Lazlo said:

    I had Covid back in February, and got positives on the S antibody - 347 - and the N antibody - 184 - in the Texas Cares study a couple of weeks ago  

    I have not been vaccinated, but always believed that I should be fine for some time without a vaccination, especially based on some preliminary studies. And, of course, got the shit negged out of me for saying so on here.

    So, what do you make of the Israeli study - or maybe analysis -  that shows that previously infected people like me have more robust protection than people with both doses of Pfizer?

    I saw a doctor that is part of the University of California system tweet statistics showing that a vaccine would be statistically irrelevant for someone like me. I don’t think he is a right wing crazy, but not sure. He was basing that on the Israeli study and a UK study.

    I’ll try to figure out how to post his tweet.

     

    The data supports your position.  Truthfully, I think we are making a big mistake by drawing a line in the sand with regards to vaccination and disregarding people in your situation.  If I were in charge, that official antibody test that proves that you had it and mounted an immune response against the virus should be good enough to count as "vaccinated" and you shouldn't be subject to any punitive measures.  At the very least they should only require you to get a single mRNA shot.  But it is what it is.  You'll probably need to get it, particularly if you want to travel and if the mandates end up sticking.

    Here is a little blurb with links to the studies that I wrote to someone who asked the same thing a little while ago:

    Studies are showing no real world benefit from getting the vaccine after recovering from infection, and there is plenty of protection to reduce the chances of reinfection and severe disease. And we also have studies demonstrating immunity from natural infection will be long lasting, possibly even providing lifetime protection, and might be more robust than vaccination alone.  With regards to vaccine breakthrough, reinfections among those who recovered from natural infection tentatively don't show as high of viral loads as those that were only vaccinated. There are a couple studies that demonstrated the neutralizing antibodies get significantly better months after infection and are able to better neutralize the variants, likely because the remnants of the virus has been shown to stay in your small bowel for months after the infection is over. This allows your immune system ample time to learn and develop a better response.

    The data on those that are getting vaccinated after recovering from COVID does show that you do get a better immune response than those that only had the vaccine or recovered from infection and there are no significant side effects from making that choice.  It is actually paradoxically good, almost like 1+1=4.  In pregnant women, getting vaccinated will provide a benefit to the child, as that boost will provide better protection during the pregnancy and while nursing after birth.

    There has been no benefit to getting the second mRNA shot in COVID recovered individuals, so if you are young and healthy and need to be vaccinated for work or travel the Johnson and Johnson shot would be a good option so you don’t have to deal with the hassle of getting the second shot.  The one exception to this is young females should probably stick with the mRNA vaccines as the risk of the rare clotting condition CVST is not observed in the Moderna or Pfizer vaccines.

    And don’t misconstrue what I’m saying.  If you haven’t had COVID the choice is still clear. Vaccination is by far your best option for gaining immunity.  The relative risks of the vaccine vs getting COVID greatly favor vaccination.

    Vaccinevsnaturalrisk.thumb.png.ea3dbb8d9712b2e772acb56828574d40.png

    The mRNA vaccines are holding up very well and appear to be generating long term immune cells, and when measuring spike specific immune responses the vaccine appears to have a slight edge on natural infection.  The difference between vaccine vs natural immunity is likely not going to be meaningful.  Say we are executing someone by firing squad, and you decide to put 11 people on the line instead of 12.  Does that really matter?

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  10. 1 hour ago, Satoshi said:

    A letter to the Lancet here addressing boosters co-signed by, among others, the two FDA vaccine officials that are quitting. 
     

     

    This is a great article.  It is nice seeing top level scientists push back against the politicians.  Some of my favorite excerpts: 

    Quote

    A consistent finding is that vaccine efficacy is substantially greater against severe disease than against any infection; in addition, vaccination appears to be substantially protective against severe disease from all the main viral variants. Although the efficacy of most vaccines against symptomatic disease is somewhat less for the delta variant than for the alpha variant, there is still high vaccine efficacy against both symptomatic and severe disease due to the delta variant.

    Quote

    Current evidence does not, therefore, appear to show a need for boosting in the general population, in which efficacy against severe disease remains high. Even if humoral immunity appears to wane, reductions in neutralising antibody titre do not necessarily predict reductions in vaccine efficacy over time, and reductions in vaccine efficacy against mild disease do not necessarily predict reductions in the (typically higher) efficacy against severe disease.

    Quote

    If vaccines are deployed where they would do the most good, they could hasten the end of the pandemic by inhibiting further evolution of variants. Indeed, WHO has called for a moratorium on boosting until the benefits of primary vaccination have been made available to more people around the world.18 This is a compelling issue, particularly as the currently available evidence does not show the need for widespread use of booster vaccination in populations that have received an effective primary vaccination regimen.

    We need to be shifting focus to get more vaccine to resource poor parts of the world where the virus is currently raging out of control.  If we are going to see a variant that can escape the vaccines to a high degree it will likely be the result of the uncontrolled spread in these areas.  This ends faster, we save more lives, and we can get the economy back to normal faster when all of humanity has access to the vaccine and not just us.   

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  11. 35 minutes ago, Brisketexan said:

    200.gif

    Cuz, umm, I don't have numbers for any of the other variables.

    I think it is safe to say that if those 600,000+ had been vaccinated a significant portion of them would have lived.  That statement shouldn't tickle any mathletic autism bones.

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  12. The UK public health system has been a wealth of information throughout the pandemic.  I've been extremely impressed with them.


    Today they published an in depth breakdown of the breakthrough cases that resulted in death among their population.

    Main points:

    Quote
    • In England, between 2 January and 2 July 2021, there were 51,281 deaths involving coronavirus (COVID-19); 640 occurred in people who were fully vaccinated, which includes people who had been infected before they were vaccinated.

    • The risk of death involving COVID-19 was consistently lower for people who had received two vaccinations compared to one or no vaccination, as shown by the weekly age-standardised mortality rates (ASMRs) for deaths involving COVID-19.

    • "Breakthrough cases" are where infection has occurred in someone who is fully vaccinated, whereas we define a "breakthrough death" as a death involving COVID-19 that occurred in someone who had received both vaccine doses and had a first positive PCR test at least 14 days after the second vaccination dose; in total, there were 256 breakthrough deaths between 2 January and 2 July 2021.

    • 61.1% of breakthrough deaths occurred in males, compared to 52.2% and 48.5% for other COVID-19 deaths and for non-COVID-19 deaths respectively; the median age of breakthrough deaths was 84, compared to 82 for other COVID-19 deaths and for non-COVID-19 deaths.

    • 13.1% of breakthrough deaths occurred in people who were identified as likely to be immunocompromised from hospital episodes or causes of death, compared to 5.4% for other COVID-19 deaths.

    Table 1 is really interesting, and shows how important the second shot is.

    Quote
    Table 1: There were 640 deaths involving COVID-19 of people who had received both vaccination doses
    Count of deaths involving COVID-19 and percentage of all deaths by vaccination status, England, deaths occurring between 2 January and 2 July 2021
    Vaccination status Deaths involving
    COVID-19
    Non-COVID-19
    deaths
    Percent of
    all deaths
    All deaths regardless of vaccination status 51,281 214,701 19.3
    Unvaccinated  38,964 65,170 37.4
    Deaths within 21 days of first dose 4,388 14,265 23.5
    Deaths 21 days or more after first dose  7,289 66,533 9.9
    Deaths within 21 days of second dose 182 11,470 1.6
    Deaths 21 days or more after second dose  458 57,263 0.8

    Source: Office for National Statistics – National Immunisation Management Service, NHS Test and Trace

    Other interesting things to note:

    The fully vaccinated COVID deaths have a median age two years older than the unvaccinated (84 vs 82) and looking at the numbers compared to the unvaccinated, we are talking about very few people relative to the overall population.  98.8% of their COVID deaths are either unvaccinated or not fully vaccinated. It is remarkable how well the vaccines are working.    

    Quote

     

    Table 3: 61.1% of breakthrough deaths occurred in males, which is higher than for other deaths involving COVID-19 and non-COVID-19 deaths
    Number and percentage of deaths occurring by various characteristics for breakthrough deaths, other deaths involving COVID-19 and non-COVID-19 deaths, England, deaths occurring between 2 January and 2 July 2021
      Breakthrough
    deaths
    Other deaths
    involving COVID-19
    Non COVID-19
    deaths
    Median age 84 82  82 
    Male 154 (61.1%)  22,819 (52.2%)  89,498 (48.5%) 
    Female 98 (38.9%)  20,885 (47.8%)  94,901 (51.5%) 
    Clinically extremely
    vulnerable
    193 (76.6%)  32,567 (74.5%)  128,454 (69.7%) 
    Not clinically
    extremely vulnerable
    59 (23.4%)  11,137 (25.5%)  55,945 (30.3%) 
    Limited a lot by
    long-term health
    problem or disability
    80 (31.7%)  12,152 (27.8%)  44,642 (24.2%) 
    Limited a little by
    long-term health
    problem or disability
    80 (31.7%)  12,604 (28.8%)  50,817 (27.6%) 
    Not limited by
    long-term health
    problem or disability
    92 (36.5%)  18,948 (43.4%)  88,940 (48.2%) 
    Immunocompromised 33 (13.1%)  2,360 (5.4%)  18,049 (9.8%) 
    Not
    immunocompromised
    219 (86.9%)  41,344 (94.6%)  166,350 (90.2%) 

    Source: Office for National Statistics – Public Health Data Asset, National Immunisation Management Service, NHS Test and Trace

     

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  13. 8 minutes ago, Anastasis said:

    Moderna flexing nuts on Pfizer.

     

    COVID-19 hospitalizations by COVID-19 vaccine
    BNT162b2 (Pfizer-BioNTech)
    Unvaccinated (ref) 6,960 1,316 (18.9)
    Fully vaccinated** 4,243 135 (3.2) 80 (73–85)
    mRNA-1273 (Moderna)
    Unvaccinated (ref) 6,960 1,316 (18.9)
    Fully vaccinated** 2,975 70 (2.4) 95 (92–97)
    Ad26.COV2.S (Janssen)
    Unvaccinated (ref) 6,960 1,316 (18.9)
    Fully vaccinated** 458 30 (6.5) 60 (31–77)
    COVID-19 ED/UC encounters by COVID-19 vaccine
    BNT162b2 (Pfizer-BioNTech)
    Unvaccinated (ref) 10,872 3,145 (28.9)
    Fully vaccinated** 3,946 314 (8.0) 77 (74–80)
    mRNA-1273 (Moderna)
    Unvaccinated (ref) 10,872 3,145 (28.9)
    Fully vaccinated** 2,656 98 (3.7) 92 (89–93)
    Ad26.COV2.S (Janssen)
    Unvaccinated (ref) 10,872 3,145 (28.9)
    Fully vaccinated** 757 100 (13.2) 65 (56–72)

    Yep.  Their decision to separate the shots by an extra week and tripling the amount of mRNA seems to be really paying off.  

    That said, I got Pfizer in January and I'm still not seeking out a booster.  In my age group it is still working fine.

  14. On 9/1/2021 at 4:02 PM, billfromlaketravis said:

    I'm listening to a podcast that analyzes the government's case: 

    https://podcasts.apple.com/us/podcast/bad-blood-the-final-chapter/id1575738174

    It was written/produced/narrated by John Carreyrou. He broke the Theranos Fraud story at the Wall Street Journal. 

    I think she walks. The destroyed hard drive makes it a she said the government said case. 

    That said, the government has a 91% conviction rate in federal court. If I had her money, I wouldn't take a plea either. 

    I'm listening to this podcast right now and I read the book.  Given this is how I make a living it is really hitting home to me.  

    CSB warning: Around 2014 Theranos sent a couple of representatives to our lab to "evaluate" their technology.  They met us in one of our conference rooms, made us sign NDAs and passed around notebooks supposedly outlining their technology.  We flipped through it and listened to their spiel.  Afterwards we said "That all sounds great, but where is your data?  I don't see anything in your presentation materials that remotely supports the claims you are making.  You are welcome to come back with data, or more ideally loan us one of your machines for us to evaluate ourselves then we can talk endorsement and sales."

    We never heard from them again. 

    She deserves to do real jail time.

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  15. An interesting MMWR was published Friday looking more specifically at the efficacy at the big three vaccines against hospitalization/severe disease against Delta and stratified the results by age.  TL;DR: Efficacy against severe disease for all three vaccines is holding up well for those under 75, but there is increasing evidence that those 75 and older will benefit from getting a booster.

    https://www.cdc.gov/mmwr/volumes/70/wr/mm7037e2.htm?s_cid=mm7037e2_w#T1_down

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