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SARS-CoV-2 Coronavirus (COVID-19)

Discussion in 'Environmental Discussion' started by tochatihu, Jan 26, 2020.

  1. tochatihu

    tochatihu Senior Member

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    There are very few chimeric mice with humanized immune systems anywhere in the world, AFAIK. Two companies in US, currently locked in patent battles? Also they are very expensive to develop. But once they exist, they can pump out antibodies to whatever you make them sick with.

    I can see that little sick chimeric mice run out of BSL containment would be a bad idea, but it probably won't happen because of their price. If you spent a million dollars on a mouse, I reckon you'd keep it on a short leash.

    It would be many steps away to produce more antibodies to more diseases in this way. I don't know if it will happen.

    My point was that such mice make gain of function research unnecessary. GoF (in this application) tweaks a virus that infects humans to also infect other species, so antibodies can be made by them. Or to develop other treatments or vaccines. Since many well-informed people consider GoF to be a really bad idea, alternatives ought to be considered to doing it.

    A few well-informed people consider GoF to be good and necessary, so take it up with them at the complaints desk.

    ==
    Well, whatever. Given how fast COVID got sequenced and mRNA vaccines were developed (which require neither of the above, not even 'growing whole viruses by any means), I expect that path to predominate when the next hot zoonotic pops up.

    Which does not mean that people will accept that vaccine, or avoid public emitting of virus until such time as adequate immunity coverage happens. Because people can be obstinate sometimes.

    I'll take it up with the complaints desk.
     
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  2. ETC(SS)

    ETC(SS) The OTHER One Percenter.....

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    De-platformed.... :unsure:

    Humans were made to be pretty adaptable.
    I'm thinking that there's going to be an up-tick in arms wanting to get jabbed before the next zoonotic bug.....
     
  3. farmecologist

    farmecologist Senior Member

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    Just want to interject a peronal story here...

    Son works at a 'Kwik trip' gas station. He is the ONLY one still wearing a mask on the job ( he wears it because he see 100s of people a day ). Last week, many of his coworkers got sick...and guess what? NONE of them had made the effort to get vaccinated. And now one of them is very ill...enough that the manager of the site*insisted* on a covid test.

    Draw your own conclusions....but I feel this is not over yet.

    Honestly...I hope that mask usage becomes MUCH more prevalent in the USA...but that is a pipe dream...because 'muh rights' ( i.e. - the ridiculous politicization of anything and everything regarding this virus ).
     
    #4163 farmecologist, Jul 23, 2021
    Last edited: Jul 23, 2021
  4. ETC(SS)

    ETC(SS) The OTHER One Percenter.....

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    People seem to forget that the Mk-1, Mod-0 old-timey FLU makes you pretty dang sick.....and if the now-redacted Brit numbers are to be believed then about 2-in-1000 younguns who get the D-flavored Vid are not going to live to see who the next President blames the future variants on.....
     
  5. tochatihu

    tochatihu Senior Member

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    @farmecologist , do you remember when hand sanitizers were all the rage? Masks are aerosol defense*. Where we still touch surfaces shared with less-informed mucus dribblers ...
    Clean hands.

    *(Imperfect, but whaddayagonnado?)
     
  6. privilege

    privilege Active Member

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    1 did the manager violate hippppa by insisting that employees share their results with him also ?

    2 why ? last I heard some of the vaccine are supposed to be 99% effective at prevention.

    3 ok this is one I have real issue with. if you don't care about the others, that's understandable. which right / rights are you ok with giving up , that you believe will end a pandemic ? for how long ? forever ?

    4 thankfully, the politics stuff usually doesn't get much speaking time. I'm glad for that.
     
  7. fuzzy1

    fuzzy1 Senior Member

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    HIPAA is not nearly as broad as very many people mistakenly think it is. I don't believe it covers this case.
    ... at preventing serious disease, hospitalization, and death. None are that effective at preventing less serious cases. And customer service employees are coming in contact with a population that includes a large fraction of un-vaccinated people.
     
  8. Trollbait

    Trollbait It's a D&D thing

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    Who likely aren't wearing masks when they can get away with it.
     
  9. bisco

    bisco cookie crumbler

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    my last concern is long term covid among the symptomatic, non hospitalized people. who knows what's in store.
    i'm still masking indoors with strangers, and just ordered a box of n95's to add to my arsenal
     
  10. Salamander_King

    Salamander_King Senior Member

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    Not exactly sure where you got this information? AFAIK, mAbs are produced in vitro by creating hybridoma by fusion of normal splenocytes from an immunized normal mouse with myeloma cells to make a clonally expandable cell line. It's been a long time since I worked on a project, but I can't remember ever using chimeric mice for mab production. And as far as chimeric mice are concerned, by definition, almost any genetically manipulated mice start as a chimeric mouse before the new genetically engineered mouse line is produced by breeding. Humanized mice are genetically engineered mice that have a human genetic sequence in their genome. They are not chimeric mice. Unless you are calling chimeric mice in the classical sense of "chimera" which is a single organism that's made up of more than two different organisms body parts. In that sense, true chimera does not exist, but there are thousands of humanized mouse strains that have been produced in labs all over the world.
     
    #4170 Salamander_King, Jul 24, 2021
    Last edited: Jul 24, 2021
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  11. bisco

    bisco cookie crumbler

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    I was wondering the same thing
     
  12. tochatihu

    tochatihu Senior Member

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    @Salamander_King is correct; there are many mice with some admixture of human genes and they are used for a wide range of biomedical research. I have been learning about these after having been smacked down by post #4170.

    For production of COVID-19 monoclonal antibodies, Regeneron appears to be leading the way. its antibody cocktail most famous customer was Donald Trump. I have seen several pharmaceutical companies with familiar names, and other startups, that are developing antibodies with their own mouse models.

    What I read about (some time ago) was Regeneron vs. Kymab legal battle over patent protection for Regeneron's particular mouse model. From that I formed an opinion that mice with humanized immune systems were rare, hot commodities, and hotly protected. Further reading today indicates that similar mice are widely used.

    From:
    Anti-SARS-CoV-2 Monoclonal Antibodies | COVID-19 Treatment Guidelines

    "Two combination products, bamlanivimab plus etesevimab and casirivimab plus imdevimab, are available through Food and Drug Administration (FDA) Emergency Use Authorizations (EUAs)"

    The first named pair are from Lilly and second from Regeneron.

    ==
    So readers may take home messages:
    Lots of mice
    Lots of research
    Two companies' MABs have EUAs
    Others may follow

    ==
    I do not intend to mislead, and appreciate disagreements because they oblige me to work towards better understanding.

    ==
    However vaccines are developed and tested, they train human immune systems more or less effectively. But there are immunocompromised people, and late-stage infections where vaccines do not help. That would appear to be best situations for MABs.
     
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  13. privilege

    privilege Active Member

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    this is messed up. I'm going to stop quoting from my phone. sheesh
     
  14. privilege

    privilege Active Member

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    I messed this post up too.

    good grief
     
  15. Salamander_King

    Salamander_King Senior Member

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    I did some online search and realized that my comment was a bit outdated. The term "monoclonal antibody" for anyone who worked on mAbs 20 years ago, like me, means a murine monoclonal antibody produced by hybridoma. Enter the 21st century COVID era, @tochatihu is talking about human monoclonal antibodies for therapeutic use. With the advent of the human monoclonal antibodies, yes, humanized antibodies and chimera antibodies are the terms often used to describe the mAbs.

    This blog post gives a very good historical background and current development on how those human monoclonal antibodies including the ones used for the treatment of COVID-19 have evolved. And according to the blog post, one of the methods used today to produce fully human monoclonal antibodies is by using humanized mice. Another method is to use Phage display technology.

    Monoclonal Antibodies: What They Are, FDA History & Future
     
    #4175 Salamander_King, Jul 24, 2021
    Last edited: Jul 24, 2021
  16. tochatihu

    tochatihu Senior Member

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    Sticking my neck out once again. I wish to say that I cannot support Gain of Function research directed at making a virus (or bacteria or fungus or other pathogen) able to infect a non-human species, to aid development of treatments for humans. Different ways to aid development of treatments for humans must be sought.

    Mice with humanized immune systems offer one alternative. Here the virus (etc.) are not upgraded. Seems like a good alternative to me.

    I wish readers were as amazed as I am by the explosive growth of genomic sequencing, and its connections to 'expressed proteins'. Any potential zoonotic can be caught and 'unzipped', by blue-gloved researchers (braver than me!). From there and yet only very recently can mRNA blueprint vaccine be developed. If funding is available :) Seems like another good alternative to me.

    For me it is simply a very good goal to widely train human immune systems for (against) the next zoonotic, whatever it may be. Alternatives to GoF research are appealing because GoF scares me right down to bone marrow.

    ==
    Anticipating zoonotics was the role of Ecosystem Health Alliance and its successor PREDICT. If they are shunned for apparent or imagined links to GoF, it would harm the human enterprise. This needs to be disentangled so that PREDICT's surveillance can continue and focus on genomics and do no GoF. Yet, to no one's surprise, I do not set policy.

    ==
    Global COVID-19 infections are now in about 20 million people and evolving towards better access to most who still have no protection. Certainly we hope this will resolve with less than 10 million dead (now <5 million). The biomedical community is all over it. The public is somewhat interested in shutting it down :eek: It will probably not be our 'resetting event'.

    Always look beyond.
     
  17. tochatihu

    tochatihu Senior Member

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    An incomplete accounting of historical pandemics:

    Bubonic plague ~540 AD 12% humans died
    Bubonic plague ~1350 AD 7% humans died
    'Spanish' influenza ~1919 3% humans died
    H1N1 influenza ~1957 1% humans died
    AIDS 1981 till now 0.5% humans died
    COVID-19 2019 till now 0.05% humans died
     
  18. privilege

    privilege Active Member

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    that's quite a perspective changer right there.
     
  19. bisco

    bisco cookie crumbler

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    provincetown, ma covid cluster from a rainy fourth of july. 430 cases so far and 3 hospitalized. doesn't seem like a bad ratio to me, and my takeaway is that we don't have to worry about this if we're vaccinated.
    37120339
     
  20. Moving Right Along

    Moving Right Along Senior Member

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    More people have died, percentage wise, from COVID than from the 1957 flu. In 1957-1958, Approximately 1 million people died out of a world population of 2.873 billion. That works out to approximately .035% of humanity. The rest of your numbers seem good.

    In the US, the 1918 flu caused the most recent time overall population decreased from one year to the next.
     
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