Recommended by Ricochet Members Created with Sketch. Day 115: COVID-19 How Are Treatments Coming?

 

Ricochet member @dong challenged me to do a post on the status of various treatments for COVID-19. As @bitcoin has said, “I am not a doctor or a virologist, but I play one on Ricochet.” So I accept @dong ‘s challenge welcoming all amendments and corrections by more knowledgeable people in the comments (most of whom undoubtedly are more knowledgeable.)

My reading of the internet is that there are four treatment paths: (1) prevent the body from getting infected, (2) attack the virus directly, (3) attack the virus indirectly, or (4) keep the body from killing itself in response to detecting the viral infection. In addition to these strategies, there are a variety of supportive therapies that are employed depending upon which organ(s) the virus is attacking. Of important note, full-intubation high-pressure ventilators may be doing more harm than good.

So let’s talk about each of the paths:

Preventing the body from getting infected

This is the vaccine approach. Making you immune from the virus itself. Totally aside from the fact that no vaccine has ever successfully been developed for any coronavirus, there are several trying to do it:

Moderna

  • Vaccine: mRNA
  • Development: Phase 1 trial near complete, phase 2 trial set to start

Johnson & Johnson

  • Vaccine: Modified adenovirus
  • Development: Preclinical

Inovio Pharmaceutical

  • Vaccine: INO-4800
  • Development: Phase 1 trials

Oxford University

  • Vaccine: ChAdOx1 nCoV-19
  • Development: Phase 1 trials

Pfizer

  • Vaccine: BNT162
  • Development: Clinical trials

Sanofi and GSK

  • Vaccine: Unnamed
  • Development: Preclinical

Novavax

  • Vaccine: NVX-CoV2373
  • Development: Preclinical

Just the sheer number of organizations in the hunt should give us some hope, but it is important to understand as you read the details of each of the vaccine plans that they are not all pursuing the same design. This is not a contest for how to get a piston engine producing the most revolutions per minute. This is designing a whole new engine with potentially different energy sources and means of converting one form of energy (heat) into another form (mechanical).

Attacking the virus directly

Remdesivir (Gilead Sciences)

Originally developed for Ebola, Remdesivir attacks the virus’s capability of replicating. Clinical data shows that it may shorten the recovery time but is not demonstrated to have saved anyone from dying. Remdesivir was granted FDA approval on May 1 for emergency use, but there are still several ongoing clinical trials testing whether it’s effective.

Favipiravir

This was initially developed to treat influenza but is being clinically trialed against COVID-19 in China, Italy, and the United Kingdom. Trials are slated to begin in Massachusetts as well. It attacks the virus by forcing mutations as it replicates neutralizing the viral effect in the body. It may be this mutation-inducing aspect that makes it not for use in pregnant women.

Attacking the virus indirectly

Eli Lilly, AstraZeneca and Regeneron, among other companies, are working on so-called antibody treatments, which are made to act like immune cells and may provide protection after exposure to the virus. Earlier this month, Regeneron said its treatment could be available for use by the end of this summer or fall.

In addition, there are two different blood therapies: convalescent plasma and healthy donor plasma. Convalescent plasma involves extracting blood plasma from recovered COVID-19 patients and infusing that plasma into active COVID-19 patients. Healthy donor plasma recently tried in Lexington, KY, has also had good clinical results. The significance of the latter is that it may be that there is a large source of life-saving substances available that are not dependent on China or a limited population of COVID-19 survivors.

Keeping the body from killing itself

Hydroxychloroquine (HCQ)

A generic malarial drug also used for treating lupus and rheumatoid arthritis. Treating COVID-19 is an “off label” application of the drug. It suppresses the body’s response to infection which in many cases is how COVID-19 kills you. Clinicians worldwide are reporting good results with HCQ in combination with zinc and azithromycin. But the drug’s effectiveness in treating COVID-19 has not been determined through traditional double-blind studies. And some worries exist that at least in some patients with heart disease, the side effects can be fatal. Its most likely success is when given early after systems present and not when someone has progressed to intensive care.

Kevzara (Regeneron and Sanofi)
Baricitinib (Eli Lilly)

Kevzara and Baricitinib are drugs currently used to treat rheumatoid arthritis. Their strategy is suppressing the body’s immune response. Clinical trials will be starting soon. In contrast to HCQ, these manufacturers see their drugs as potentially effective for patients who have progressed to intensive care.

This is the landscape at the moment. No doubt more news is to come.

[Note: Links to all my COVID-19 posts can be found here.]

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  1. Mendel Member
    Mendel Joined in the first year of Ricochet Ricochet Charter Member

    Nice summary, Rodin. As a former virologist I could add quite a bit here, but I don’t have enough time.

    However, there is one development that’s not getting anywhere near enough reporting: a Chinese company has developed and starting testing a SARS-CoV vaccine based on the exact same principle and manufacturing process as the Salk polio vaccine. They’ve already tested the vaccine in monkeys (which is a fairly big deal and more than most competitors have done), and the monkeys are 100% protected with no side effects, including antibody-dependent enhancement.

    Several reasons why this is important. First, the Salk vaccine is a proven technology that we know can work. None of the other first-tier candidates have ever been proven to work for any infectious disease. In fact, many of them have been in development for decades and failed (even multiple times) in other settings.

    Second, the Salk vaccine is one of the best-known vaccines in the world, so we can be quite certain of its safety (both the vaccine itself and the manufacturing process) without exhaustive testing. Finally, millions of doses of Salk vaccine are still produced every year. Those facilities could be very rapidly retooled to produce the SARS-CoV-2 vaccine, as the process would be nearly identical, and humanity would definitely survive one year of slightly fewer polio vaccinations. Since all of the other vaccines have never left the experimental phase, there are no large-scale production facilities for any of them, nor have their manufacturing methods been validated by the FDA. In summary, a Salk-like vaccine could probably reach the level of 100 million doses 6 months to 1 year faster than these experimental vaccines.

    The problem is that “Big Vaccine” is no longer interested in 1950s technology. This includes both the Western pharmaceutical industry as well as major NGOs (and Bill Gates) and the WHO. Big Pharma can’t make much money off this, and Gates and the NGO jet set crowd don’t find it sexy enough (no joke). It’s true that most vaccines produced by a Salk-style vaccine are somewhat less potent than those using more modern technologies. But even a somewhat weak vaccine could probably do wonders, since transmission of the virus doesn’t appear to be as aggressive as originally believed.

    In summary, it’s ridiculous that mainstream science is poo-pooing a tried-and-true method that a) has been proven for decades, b) is very reliable, and c) could be ramped up months or years more quickly. And it’s embarrassing that the Chinese did it first. In my opinion, US-based rhesus macaque laboratories should be repeating these experiments right now to confirm the Chinese research. If the results prove reproducible, let’s beat the Chinese at their own game by confiscating their intellectual property to manufacture the virus ourselves.

    Link to the study: https://science.sciencemag.org/content/early/2020/05/06/science.abc1932

    • #1
    • May 14, 2020, at 8:44 AM PDT
    • 23 likes
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  2. Kozak Member
    Kozak Joined in the first year of Ricochet Ricochet Charter Member

    Rodin:

    Hydroxychloroquine (HCQ)

    A generic malarial drug also used for treating lupus and rheumatoid arthritis. Treating COVID-19 is an “off label” application of the drug. It suppresses the body’s response to infection which in many cases is how COVID-19 kills you. Clinicians world-wide are reporting good results with HCQ in combination with zinc and azithromycin. But the drug’s effectiveness in treating COVID-19 has not been determined through traditional double-blind studies. And some worries exist that at least in some patients with heart disease, the side effects can be fatal. Its most likely success is when given early after systems present and not when someone has progressed to intensive care.

     

    Heres a treatment protocol from Eastern Virginia Medical School.

    Early on it appears HCQ may be effective. The theory is it blocks viral replication if used early. As the disease progresses it , and other antivirals loose efficacy. Then treatment shifts to treating the cytokine storm and subsequent microvascular inflammation and clotting disorder.

    Summary of EVMS Treatment Protocol.

     

     

    Link to the entire EVMS Treatment Protocol

     

     

    • #2
    • May 14, 2020, at 8:48 AM PDT
    • 13 likes
  3. cdor Member
    cdor Joined in the first year of Ricochet Ricochet Charter Member

    Aren’t safe and effective vaccines the most difficult and time-consuming, albeit absolute (relatively speaking) solutions? While we are waiting the several years, if at all, for a vaccine, which of the treatments are the most effective? Whatever happened with the hydroxychloroquine studies?

    • #3
    • May 14, 2020, at 9:02 AM PDT
    • 7 likes
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  4. Locke On Member

    There are several short talks and a discussion of vaccines and therapeutics in this UCSF Grand Rounds video from a week ago:

    I cued it at the relevant spot, but there’s interesting stuff before that as well, just not as on point.

    Note the mention of HCQ studies as being dropped in favor of therapeutics with similar mechanisms, due to the know heart damage risk.

    @mendel ‘s info about a Salk approach is very interesting.

    • #4
    • May 14, 2020, at 9:03 AM PDT
    • 6 likes
    • This comment has been edited.
  5. cdor Member
    cdor Joined in the first year of Ricochet Ricochet Charter Member

    Locke On (View Comment):

    There are several short talks and a discussion of vaccines and therapeutics in this UCSF Grand Rounds video from a week ago:

    I cued it at the relevant spot, but there’s interesting stuff before that as well, just not as on point.

    Note the mention of HCQ studies as being dropped in favor of therapeutics with similar mechanisms, due to the know heart damage risk.

    @mendel ‘s info about a Salk approach is very interesting.

    I am confused about the known heart damage risk of Hydroxy… Hasn’t the drug been used extensively for 6 or 7 decades? Is the heart damage risk higher because it is “off-label” ?

    • #5
    • May 14, 2020, at 9:12 AM PDT
    • 5 likes
  6. Rodin Member
    Rodin

    cdor (View Comment):
    Whatever happened with the hydroxychloroquine studies?

    The formal studies are still under way. Clinical anecdotes for success were referenced in the OP. An “observational study” was published in the JAMA Open Network that discounted the efficacy of the treatment, but

    Observational studies aren’t considered as conclusive as randomized controlled trials, because doctors can prescribe a variety of other drugs to treat an infection. The less formal process, however, can yield faster results and help with the approval process of some treatments.

    There are also critics of this observational study that think it was just way too convenient to publicize criticism of a therapy that President Trump was telling people about.

    • #6
    • May 14, 2020, at 9:15 AM PDT
    • 5 likes
  7. Unsk Member

    Early on it appears HCQ may be effective. The theory is it blocks viral replication if used early. As the disease progresses it , and other antivirals loose efficacy.

    If the Viral load has progressed too far HCQ will lose it’s effectiveness. But if used in the early stages it has been proven worldwide to be very effective. HCQ has been used since 1955 and has been used by millions. It is safe. That said HCQ should be used with AZITHROMYCIN only in those patients without heart issues. Doctors have used HCQ with Zinc with good success for those patients with heart issues. The Dr Fauci/Big Pharma/Big Media Cabal has effectively promulgated the lie that HCQ is dangerous when at this time it is far and away the best remedy out there in the early stages against the virus. It’s use has saved thousands of lives. 

    Remdesivir attacks the virus’ capability of replicating. Clinical data shows that it may shorten the recovery time but is not demonstrated to have saved anyone from dying. Remdesivir was granted FDA approval on May 1 for emergency use-

    The phrase “is not demonstrated to have saved anyone from dying” should be repeated load and clear, over and over. Remdesirvir has not been shown to save lives and the study used for it’s approval was abruptly corruptly reconfigured midstream to show at least some effectiveness in reducing symptoms but it was shown that Remdesirvir was failing to save lives, so why has the FDA granted it approval for emergency use and not HCQ? This fact shows the blatant corruption of Fauci ,the FDA and the NIH. Remdesirvir so far has not been shown to work. 

    • #7
    • May 14, 2020, at 9:22 AM PDT
    • 13 likes
  8. Rodin Member
    Rodin

    cdor (View Comment):

    Locke On (View Comment):

    There are several short talks and a discussion of vaccines and therapeutics in this UCSF Grand Rounds video from a week ago:

    I cued it at the relevant spot, but there’s interesting stuff before that as well, just not as on point.

    Note the mention of HCQ studies as being dropped in favor of therapeutics with similar mechanisms, due to the know heart damage risk.

    @mendel ‘s info about a Salk approach is very interesting.

    I am confused about the known heart damage risk of Hydroxy… Hasn’t the drug been used extensively for 6 or 7 decades? Is the heart damage risk higher because it is “off-label” ?

    The heart risk is not because it is “off-label.” If you have a patient with both lupus and arrhythmia or rheumatoid arthritis and arrhythmia the treating physician would be monitoring the use of HCQ closely or not prescribing it. The potential heart issues is a known side effect and have to be weighed by the physician when considering the health history of the specific patient. That does not make HCQ a bad therapy. It just means that the potential side effect has to be considered in deciding a course of therapy. That is true for all drugs.

    • #8
    • May 14, 2020, at 9:27 AM PDT
    • 12 likes
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  9. DonG (skeptic) Coolidge

    I am still confused about how after 8 weeks of HCQ talk in the news and 1,000,000+ patients, that we still don’t have definitive data on treatments. I appreciate the EVMS protocol and I suspect many locales have developed something similar, despite not having good studies on HCQ and other treatments. I can’t help but think that some powerful entity is stopping the research at the national level.

    I find it interesting that EVMS recommends Vitamin-D. I came across another study about Vitamin-D and Covid19 out of Ireland. Every state should require every nursing home to begin prophylactic vitamin-D/C/Zinc supplements. Every nursing home should do it without a government telling them to. Every nursing home resident should get a care package from their family today. This is from the study:

    The northern latitude countries of Norway, Finland and Sweden, have higher vitamin D levels despite less UVB sunlight exposure, because supplementation and fortification of foods is more common.

    This study further confirms this association. We call on the Irish government to update guidelines as a matter of urgency and encourage all adults to take supplements during the COVID-19 crisis. Deficiency is frequent in Ireland. Deficiency is most prevalent with age, obesity, in men, in ethnic minorities, in people with diabetes, hypertension and in nursing homes

    This is a situation, where knowledgeable people are ahead of the experts. @ronin thank you for the informative summary.

    • #9
    • May 14, 2020, at 9:30 AM PDT
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  10. Mendel Member
    Mendel Joined in the first year of Ricochet Ricochet Charter Member

    The HCQ topic still remains an absolute dumpster fire.

    The side effects of HCQ alone appear to be mostly overblown. In the studies that claim to show HCQ toxicity, it is usually because a) the treatment was not randomly assigned, meaning the patients who get HCQ tend to be sicker and were already predestined to have worse outcomes, b) it was given at very high doses, or c) it was given in combination with azithromycin. That last factor does seem to be problematic.

    Every single study on the benefits of HCQ so far has had major methodological flaws. Without exception (I’ve read almost all of them). This includes both studies purporting to show benefit, and studies purporting to show no benefit.

    There are ongoing randomized clinical trials that administer the drug in different settings/time points/patients that have yet to report their results. Hopefully these will be forthcoming.

    Also, the “lupus patients taking HCQ for years don’t get severe disease” claim seems to have been clearly refuted.

    All in all, we still don’t know much more about this topic than we did a month ago. Frustrating.

    • #10
    • May 14, 2020, at 9:38 AM PDT
    • 16 likes
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  11. cdor Member
    cdor Joined in the first year of Ricochet Ricochet Charter Member

    Rodin (View Comment):

    cdor (View Comment):

    Locke On (View Comment):

    There are several short talks and a discussion of vaccines and therapeutics in this UCSF Grand Rounds video from a week ago:

    I cued it at the relevant spot, but there’s interesting stuff before that as well, just not as on point.

    Note the mention of HCQ studies as being dropped in favor of therapeutics with similar mechanisms, due to the know heart damage risk.

    @mendel ‘s info about a Salk approach is very interesting.

    I am confused about the known heart damage risk of Hydroxy… Hasn’t the drug been used extensively for 6 or 7 decades? Is the heart damage risk higher because it is “off-label” ?

    The heart risk is not because it is “off-label.” If you have a patient with both lupus and arrhythmia or rheumatoid arthritis and arrhythmia the treating physician would be monitoring the use of HCQ closely or not prescribing it. The potential heart issues is a known side effect and have to be weighed by the physician when considering the health history of the specific patient. That does not make HCQ a bad therapy. It just means that the potential side effect has to be considered in deciding a course of therapy. That is true for all drugs.

    Anyone who has ever listened to an advertisement for any medication, even aspirin, on TV is well aware that ALL drugs can have negative side effects. A person with any number of immune compromising issues must always be careful of the medications they take under any circumstance. I was surprised to hear a week or so ago about this new and now, newly approved drug called Remdesirvir. It seems to have popped up out of nowhere. I have seen no actual results, even anecdotal, mentioned. Yet with the Chloroquine medication, it seems that thousands of anecdotal success stories have been documented and I have heard of very minimal if any, negative reactions. It is cheap and completely and thoroughly observed. What am I missing?

     

    • #11
    • May 14, 2020, at 9:41 AM PDT
    • 7 likes
  12. Mendel Member
    Mendel Joined in the first year of Ricochet Ricochet Charter Member

    cdor (View Comment):
    Yet with the Chloroquine medication, it seems that thousands of anecdotal success stories have been documented and I have heard of very minimal if any, negative reactions. It is cheap and completely and thoroughly observed. What am I missing?

    You’re not missing anything. It’s the fact that those success stories are anecdotal. Anecdotal stories are very good to know but don’t provide enough confidence that the result isn’t a fluke. And that is doubly the case for an infection that the vast majority of patients will survive just fine without any treatment at all.

    So statistically speaking, it would not be unusual for a single clinic that sees only 25 Covid patients to have only a small number if not no severe cases or deaths at all. Now that same clinic decides to test their bright new therapeutic idea on some or all of their patients. And what do they see? 100% success!

    Does that mean the drug worked, or were they just fooled by randomness? There’s no way to know without large-scale, uniform trials. And those trials take time.

     

    • #12
    • May 14, 2020, at 9:47 AM PDT
    • 10 likes
  13. cdor Member
    cdor Joined in the first year of Ricochet Ricochet Charter Member

    Mendel (View Comment):

    The HCQ topic still remains an absolute dumpster fire.

    The side effects of HCQ alone appear to be mostly overblown. In the studies that claim to show HCQ toxicity, it is usually because a) the treatment was not randomly assigned, meaning the patients who get HCQ tend to be sicker and were already predestined to have worse outcomes, b) it was given at very high doses, or c) it was given in combination with azithromycin. That last factor does seem to be problematic.

    Every single study on the benefits of HCQ so far has had major methodological flaws. Without exception (I’ve read almost all of them). This includes both studies purporting to show benefit, and studies purporting to show no benefit.

    There are ongoing randomized clinical trials that administer the drug in different settings/time points/patients that have yet to report their results. Hopefully these will be forthcoming.

    Also, the “lupus patients taking HCQ for years don’t get severe disease” claim seems to have been clearly refuted.

    All in all, we still don’t know much more about this topic than we did a month ago. Frustrating.

    Thank you @mendel. Yes, this is very frustrating for me as well. I am trying to avoid theories, but it is difficult to not notice the negative effect of Trump saying, “What have you got to lose?” on the perception of this drug. I hear people talk about it with such venom and disdain that it feels like it is poison.

     

    • #13
    • May 14, 2020, at 9:51 AM PDT
    • 6 likes
  14. CarolJoy, Above Top Secret Coolidge

    Those of us who have been vax injured or who have family members who suffered that fate, are never going to take a vax for this. Given that it will be RNA based, and will also, as Fauci has bragged, need to have nano bot technology to somehow ensure that it is effective, I do not consent to being a guinea pig.

    If hydroxycloroquine was an item that Bill Gates held the patent to, and if it cost at least 1100 bucks per treatment, rather than the 20 bucks a month it now costs, it would already be mandated. As it is, its use has been suppressed.

    Also Bill Gates and/or his proxies in New York are now doing the research and studies. This would have been a major conflict of interest, such that had this been happening 60 years ago,e very other critter in Congress would have been screaming about the inappropriateness of having this billionaire being in charge of the HCQ research.

     

    • #14
    • May 14, 2020, at 10:59 AM PDT
    • 6 likes
  15. CarolJoy, Above Top Secret Coolidge

    Here are two different takes on Zev Zelenko and his use of hydroxychloroquine:

    https://www.nytimes.com/2020/04/02/technology/doctor-zelenko-coronavirus-drugs.html
    How Zev went from a country doctor to a man who had the President’s attention:
    By Kevin Roose and Matthew Rosenberg

    April 2, 2020

    Last month, residents of Kiryas Joel, a New York village of 35,000 Hasidic Jews roughly an hour’s drive from Manhattan, began hearing about a promising treatment for the coronavirus that had been rippling through their community.

    The source was Dr. Vladimir Zelenko, 46, a mild-mannered family doctor with offices near the village. Since early March, his clinics had treated people with coronavirus-like symptoms, and he had developed an experimental treatment consisting of an antimalarial medication called hydroxychloroquine, the antibiotic azithromycin and zinc sulfate.

    Full article at link above.

    Here is another article on how the simple inexpensive cocktail brought forward by Zev Zelenko has helped his patients:

    https://www.vanguardngr.com/2020/03/coronavirus-new-york-doctor-successfully-treats-patients-with-drug-cocktail/

     

    • #15
    • May 14, 2020, at 11:07 AM PDT
    • 4 likes
  16. MichaelKennedy Coolidge

    Mendel (View Comment):
    The problem is that “Big Vaccine” is no longer interested in 1950s technology. This includes both the Western pharmaceutical industry as well as major NGOs (and Bill Gates) and the WHO. Big Pharma can’t make much money off this, and Gates and the NGO jet set crowd don’t find it sexy enough (no joke). It’s true that most vaccines produced by a Salk-style vaccine are somewhat less potent than those using more modern technologies. But even a somewhat weak vaccine could probably do wonders, since transmission of the virus doesn’t appear to be as aggressive as originally believed.

    Hillary Clinton killed off the vaccine”industry” by taking over the vaccine production.

    https://nypost.com/2015/10/18/hillarys-vaccine-price-plan-didnt-work-the-first-time-for-a-reason/

    The WSJ story is behind a pay wall.

    As first lady and in charge of the Bill Clinton administration’s health-care reform effort, Hillary accused “greedy” drug companies of exorbitant price increases for vaccines. In 1993, she first proposed nationalizing the vaccine industry. She settled for a Vaccines for Children Program that saw the federal government buy up over half of all available vaccines at government-set prices.

    The result? Companies stopped producing and investing in vaccines. The United States started experiencing vaccine shortages.

    In 1994, the Health Security Act called for the federal government to deny coverage for Medicare patients using drugs deemed “excessively priced” by a public commission. Under the Clinton plan, physicians or pharmacists had to obtain prior approval from the government before prescribing or dispensing to Medicare patients a drug deemed not cost-effective.

    Back then, Hillary’s advisers — doctors pretending to be economists — told biotech startups to focus on big targets like heart attacks instead of on rare illnesses like cystic fibrosis and
    Gaucher’s disease. You see, these “experts” were confident that the government and insurers could come up with “reasonable” prices for new medicines and determine which ones were really necessary.

    The biotechnology industry took years to recover.

    Thank you, Hillary.

    • #16
    • May 14, 2020, at 11:21 AM PDT
    • 10 likes
  17. cdor Member
    cdor Joined in the first year of Ricochet Ricochet Charter Member

    CarolJoy, Above Top Secret (View Comment):
    If hydroxycloroquine was an item that Bill Gates held the patent to, and if it cost at least 1100 bucks per treatment, rather than the 20 bucks a month it now costs, it would already be mandated. As it is, its use has been suppressed.

    The first week of March my wife and I returned from a few weeks in Mexico. The scare was beginning to take hold. I heard Ingraham discuss Hydroxy… on her show. I was able to get a dose for my wife and myself, just in case. The two doses together cost me $1.50 out of pocket. A dose means to me 14 pills, four the first day and two each day for five days thereafter.

    • #17
    • May 14, 2020, at 11:58 AM PDT
    • 7 likes
  18. Jerry Giordano (Arizona Patrio… Member

    Mendel (View Comment):
    The HCQ topic still remains an absolute dumpster fire.

    How true, and on both sides. I find it very frustrating, as well.

    Personally, I encounter more people who are insistent that HCQ has been proven effective, and seem impervious to evidence that this is not the case. I occasionally see reports of people who insist that HCQ cannot possibly be effective, apparently because if it was, they would have to admit that the President was right about something.

    Thanks for your update, frustrating as it is to have no answer to this question.

    • #18
    • May 14, 2020, at 12:34 PM PDT
    • 6 likes
  19. Kozak Member
    Kozak Joined in the first year of Ricochet Ricochet Charter Member

    cdor (View Comment):
    I am confused about the known heart damage risk of Hydroxy… Hasn’t the drug been used extensively for 6 or 7 decades? Is the heart damage risk higher because it is “off-label” ?

    It doesn’t cause heart damage.

    It causes “QT prolongation”. It affects the way the heart muscle repolarizes after a beat. It takes longer to do so.

    This allows the possibility of developing a sudden cardiac arrhythmia called Torsades de Pointe, a form of ventricular tachycardia that can be fatal. A lot of drugs can do this. It’s also something that is cumulative, the more QT prolonging drugs you take the, the more at risk you are. The risk is small, but real. What I have not been able to determine is “how small”? One in a thousand? One in a million?

    The problem has been recognized in Rheumatologic patients who have been taking HCQ for long periods of time, it just has not had a major study. My best guess is that it’s a minor if real risk.

    Here’s a study looking at this from a Rheumatology journal.

    Personally, if I need to take it, or prescribe it, the answer is to monitor the EKG on a daily basis for changes.

     

    • #19
    • May 14, 2020, at 12:47 PM PDT
    • 9 likes
  20. cdor Member
    cdor Joined in the first year of Ricochet Ricochet Charter Member

    Kozak (View Comment):

    cdor (View Comment):
    I am confused about the known heart damage risk of Hydroxy… Hasn’t the drug been used extensively for 6 or 7 decades? Is the heart damage risk higher because it is “off-label” ?

    It doesn’t cause heart damage.

    It causes “QT prolongation”. It affects the way the heart muscle repolarizes after a beat. It takes longer to do so.

    This allows the possibility of developing a sudden cardiac arrhythmia called Torsades de Pointe, a form of ventricular tachycardia that can be fatal. A lot of drugs can do this. It’s also something that is cumulative, the more QT prolonging drugs you take the, the more at risk you are. The risk is small, but real. What I have not been able to determine is “how small”? One in a thousand? One in a million?

    The problem has been recognized in Rheumatologic patients who have been taking HCQ for long periods of time, it just has not had a major study. My best guess is that it’s a minor if real risk.

    Here’s a study looking at this from a Rheumatology journal.

    Personally, if I need to take it, or prescribe it, the answer is to monitor the EKG on a daily basis for changes.

     

    Without the professional detail that you, @kozak , infused into your answer, I had read and been told by my own Doctor about the known side effect you described. Thanks for the deeper explanation. If you contracted this disease, would you take Hydroxy…? 

    • #20
    • May 14, 2020, at 1:47 PM PDT
    • 3 likes
  21. MiMac Thatcher
    1. prolonged QT is a problem with many medications and it can be additive-hence the concern with zithromycin & HCQ-as well as other medications the patient may be on.
    2. it is unlikely the ventilator is the problem with COVID patients-those that need the vent are the very sickest patients. As a famous doctor said – sick patients are the ones that die. Ventilator associated lung injury is a well known problem-but that doesn’t mean you avoid ventilating patients that need it. Proning is a method to help decrease the risk of injury-and is also a well known strategy in ARDS patients.
    3.  HCQ isn’t proven and one needs to be careful giving drugs that suppress the immune system to patients fighting an infection-for the obvious reason that when fighting an infection we want the immune system to be at its prime. Such drugs may prove effective if the main problem is the so called cytokine storm-ie the main source of damage is the immune systems reaction to the infection. But even this is poorly understood.
    4.  Many claims of successful therapy need to be taken with a grain of salt-since so many patients have mild or no symptoms. If i give a drug cocktail to a patient early in the course & he improves, how do I know he wasn’t destined to have a mild case in any event? On the other hand, if I choose to wait until he is really sick might I have missed the opportunity to save him?
    • #21
    • May 14, 2020, at 2:59 PM PDT
    • 7 likes
    • This comment has been edited.
  22. Ontheleftcoast Member

    Re: Therapeutics

    So-called high dose vitamin C is being trialed in China and is in use in NYC area hospitals, where 1600 mg 3-4 times/d is given. This dosage has been found safe in Phase I trials in adjunctive regimens in sepsis though much higher doses are used by some doctors. There are numerous case/anecdodal reports are using doses at least 25 times higher with few problems other than easily managed hypoglycemia. See also the “well tolerated” doses mentioned below for burns:

    It has been shown in healthy volunteers that high-level ascorbic acid plasma concentrations could only be achieved by intravenous administration, not by enteral intake. In most studies, doses as high as 1 to 2 g q8h of ascorbate were administered intravenously. In burned patients, a very high dose of ascorbate (1,584 mg/kg/day) was well tolerated, and associated with a significant reduction in fluid intake, pulmonary dysfunction, and tissue edema. In the recent study mentioned above, Marik et al. administered 1500 mg vitamin C IV q6, thiamine 200 mg q12 for 4 days, or until ICU discharge, and 50 mg hydrocortisone IV q6 (optional 50 mg bolus, followed by a 24-hour continuous infusion of 200 mg) for 4 days.

    Dr. Zelenko is working on a publication describing his work with HCQ; he said that he is trying to make it absolutely “bulletproof.” Here’s a recent interview. It is clearly not a good treatment for advanced disease, though many medical personnel in the COVID trenches are reportedly taking it prophylactically and/or keep it on hand for possible therapeutic need for themselves and their families.

    I’m hearing that the body temperature tracking feature of the Oura ring is an early warning sign of an infection brewing, though that obviously isn’t pathognomonic for SARS-CoV-2. A study involving 30,000 ring bearers is underway; more specific patterns might emerge. Or not.

    Hydrogen (the gas, not hydrogen peroxide) is also being investigated.

     

     

    • #22
    • May 14, 2020, at 3:10 PM PDT
    • 4 likes
  23. MISTER BITCOIN Member

    Mendel (View Comment):

    Nice summary, Rodin. As a former virologist I could add quite a bit here, but I don’t have enough time.

    Link to the study: https://science.sciencemag.org/content/early/2020/05/06/science.abc1932

    What about the other polio vaccine?

     

    • #23
    • May 14, 2020, at 3:17 PM PDT
    • 1 like
  24. Lockdowns are Precious Inactive
    Lockdowns are Precious Joined in the first year of Ricochet Ricochet Charter Member

    So-called high dose vitamin C is being trialed in China and is in use in NYC area hospitals, where 1600 mg 3-4 times/d is given.

    Well, you may want to read the recommendations of the doctor who helped convince the Shanghai, China government to make it an official recommendation. 1,600 mg twice a day? I’ve taken 25 grams (25,000 mg) in a mixed IV and consumed it in one hour less than 4 weeks ago. Much to the chagrin of many, I’m still alive here to talk about it. That dose was low because of shortages. I actually wanted 50 grams.

    • #24
    • May 14, 2020, at 3:19 PM PDT
    • 3 likes
  25. MISTER BITCOIN Member

    Kozak (View Comment):

    Rodin:

    Hydroxychloroquine (HCQ)

    A generic malarial drug also used for treating lupus and rheumatoid arthritis. Treating COVID-19 is an “off label” application of the drug. It suppresses the body’s response to infection which in many cases is how COVID-19 kills you. Clinicians world-wide are reporting good results with HCQ in combination with zinc and azithromycin. But the drug’s effectiveness in treating COVID-19 has not been determined through traditional double-blind studies. And some worries exist that at least in some patients with heart disease, the side effects can be fatal. Its most likely success is when given early after systems present and not when someone has progressed to intensive care.

     

    Heres a treatment protocol from Eastern Virginia Medical School.

    Early on it appears HCQ may be effective. The theory is it blocks viral replication if used early. As the disease progresses it , and other antivirals loose efficacy. Then treatment shifts to treating the cytokine storm and subsequent microvascular inflammation and clotting disorder.

    Summary of EVMS Treatment Protocol.

     

     

    Link to the entire https://www.evms.edu/covid-19/medical_information_resources/#covidcare

    fixed typo in link

     

     

    • #25
    • May 14, 2020, at 3:22 PM PDT
    • 4 likes
  26. MISTER BITCOIN Member

    cdor (View Comment):

    Locke On (View Comment):

    There are several short talks and a discussion of vaccines and therapeutics in this UCSF Grand Rounds video from a week ago:

    I cued it at the relevant spot, but there’s interesting stuff before that as well, just not as on point.

    Note the mention of HCQ studies as being dropped in favor of therapeutics with similar mechanisms, due to the know heart damage risk.

    @mendel ‘s info about a Salk approach is very interesting.

    I am confused about the known heart damage risk of Hydroxy… Hasn’t the drug been used extensively for 6 or 7 decades? Is the heart damage risk higher because it is “off-label” ?

    FDA approved in 1955

     

    • #26
    • May 14, 2020, at 3:23 PM PDT
    • 4 likes
  27. Lockdowns are Precious Inactive
    Lockdowns are Precious Joined in the first year of Ricochet Ricochet Charter Member

    Chloroquine Is a Zinc Ionophore

    Chloroquine is an established antimalarial agent that has been recently tested in clinical trials for its anticancer activity. The favorable effect of chloroquine appears to be due to its ability to sensitize cancerous cells to chemotherapy, radiation therapy, and induce apoptosis. The present study investigated the interaction of zinc ions with chloroquine in a human ovarian cancer cell line (A2780). Chloroquine enhanced zinc uptake by A2780 cells in a concentration-dependent manner, as assayed using a fluorescent zinc probe. This enhancement was attenuated by TPEN, a high affinity metal-binding compound, indicating the specificity of the zinc uptake. Furthermore, addition of copper or iron ions had no effect on chloroquine-induced zinc uptake. Fluorescent microscopic examination of intracellular zinc distribution demonstrated that free zinc ions are more concentrated in the lysosomes after addition of chloroquine, which is consistent with previous reports showing that chloroquine inhibits lysosome function. The combination of chloroquine with zinc enhanced chloroquine’s cytotoxicity and induced apoptosis in A2780 cells. Thus chloroquine is a zinc ionophore, a property that may contribute to chloroquine’s anticancer activity.

    Layman’s summary: It opens up a dedicated channel for zinc into the cell. This is much more difficult to achieve under normal conditions, hence the elevated zinc consumption protocol of roughly 200 mg for up to 5 days.

    We have previously reported that zinc ions exhibit anticancer activity by altering lysosome membrane permeability [15] and via gene expression regulation [16]. Zinc binding compounds, especially zinc ionophores, are a new group of potential anticancer agents that target zinc to the lysosomes and induce lysosome-mediated apoptosis of cancer cells [17]. In addition, the role of zinc in regulating autophagy has been recently realized [18]. Whereas previous studies have found that metal containing chloroquine complexes may lead to enhanced antimalarial activity [19], its interaction with zinc ions has never been investigated in any biological system. Given the reported anticancer activity of zinc ions and chloroquine and their involvement in lysosomal functions, we sought to investigate whether zinc ions interact with chloroquine and whether this interaction alters chloroquine’s anticancer activity. We report that chloroquine is a zinc ionophore, which targets zinc to the lysosomes, and that the combination of zinc and chloroquine enhances their cytotoxicity and induces apoptosis in a human cancer cell model system.

    • #27
    • May 14, 2020, at 3:40 PM PDT
    • 5 likes
  28. MISTER BITCOIN Member

    Bill Gates Will Inject You Now (View Comment):

    Chloroquine Is a Zinc Ionophore

    Chloroquine is an established antimalarial agent that has been recently tested in clinical trials for its anticancer activity. The favorable effect of chloroquine appears to be due to its ability to sensitize cancerous cells to chemotherapy, radiation therapy, and induce apoptosis. The present study investigated the interaction of zinc ions with chloroquine in a human ovarian cancer cell line (A2780). Chloroquine enhanced zinc uptake by A2780 cells in a concentration-dependent manner, as assayed using a fluorescent zinc probe. This enhancement was attenuated by TPEN, a high affinity metal-binding compound, indicating the specificity of the zinc uptake. Furthermore, addition of copper or iron ions had no effect on chloroquine-induced zinc uptake. Fluorescent microscopic examination of intracellular zinc distribution demonstrated that free zinc ions are more concentrated in the lysosomes after addition of chloroquine, which is consistent with previous reports showing that chloroquine inhibits lysosome function. The combination of chloroquine with zinc enhanced chloroquine’s cytotoxicity and induced apoptosis in A2780 cells. Thus chloroquine is a zinc ionophore, a property that may contribute to chloroquine’s anticancer activity.

    Layman’s summary: It opens up a dedicated channel for zinc into the cell. This is much more difficult to achieve under normal conditions, hence the elevated zinc consumption protocol of roughly 200 mg for up to 5 days.

    We have previously reported that zinc ions exhibit anticancer activity by altering lysosome membrane permeability [15] and via gene expression regulation [16]. Zinc binding compounds, especially zinc ionophores, are a new group of potential anticancer agents that target zinc to the lysosomes and induce lysosome-mediated apoptosis of cancer cells [17]. In addition, the role of zinc in regulating autophagy has been recently realized [18]. Whereas previous studies have found that metal containing chloroquine complexes may lead to enhanced antimalarial activity [19], its interaction with zinc ions has never been investigated in any biological system. Given the reported anticancer activity of zinc ions and chloroquine and their involvement in lysosomal functions, we sought to investigate whether zinc ions interact with chloroquine and whether this interaction alters chloroquine’s anticancer activity. We report that chloroquine is a zinc ionophore, which targets zinc to the lysosomes, and that the combination of zinc and chloroquine enhances their cytotoxicity and induces apoptosis in a human cancer cell model system.

    the combination of zine and chloroquine induces apoptosis in a human cancer cell model system?

    zinc + chloroquine = kill cancer cells?

     

    • #28
    • May 14, 2020, at 3:47 PM PDT
    • 1 like
  29. Lockdowns are Precious Inactive
    Lockdowns are Precious Joined in the first year of Ricochet Ricochet Charter Member

    MISTER BITCOIN (View Comment):

    Bill Gates Will Inject You Now (View Comment):

    Chloroquine Is a Zinc Ionophore

    ..

    Layman’s summary: It opens up a dedicated channel for zinc into the cell. This is much more difficult to achieve under normal conditions, hence the elevated zinc consumption protocol of roughly 200 mg for up to 5 days.

    We have previously reported that zinc ions exhibit anticancer activity by altering lysosome membrane permeability [15] and via gene expression regulation [16]. Zinc binding compounds, especially zinc ionophores, are a new group of potential anticancer agents that target zinc to the lysosomes and induce lysosome-mediated apoptosis of cancer cells [17]. In addition, the role of zinc in regulating autophagy has been recently realized [18]. Whereas previous studies have found that metal containing chloroquine complexes may lead to enhanced antimalarial activity [19], its interaction with zinc ions has never been investigated in any biological system. Given the reported anticancer activity of zinc ions and chloroquine and their involvement in lysosomal functions, we sought to investigate whether zinc ions interact with chloroquine and whether this interaction alters chloroquine’s anticancer activity. We report that chloroquine is a zinc ionophore, which targets zinc to the lysosomes, and that the combination of zinc and chloroquine enhances their cytotoxicity and induces apoptosis in a human cancer cell model system.

    the combination of zine and chloroquine induces apoptosis in a human cancer cell model system?

    zinc + chloroquine = kill cancer cells?

    That’s the claim. I’m more familiar with Vitamin C being used as adjunctive therapy in that model (the Riordan Clinic uses it as a mainstay) both with and without Ozone preceding it and glutathione as an additional ingredient along with Magnesium Chloride so I don’t know how you sequence this on an actual patient under continuing long term care. The more important thing I wanted to highlight was the well known mechanism that its proven under imaging that it opens up a dedicated zinc channel. That’s no small accomplishment, and the channel is well documented.

    The challenge under cancer care is not inducing such a toxin release that you overwhelm the patient in a single treatment but manage the cancer cell kill and what it releases (I’m thinking of iron) properly.

     

    • #29
    • May 14, 2020, at 3:56 PM PDT
    • 2 likes
  30. Ontheleftcoast Member

    Bill Gates Will Inject You Now (View Comment):

    Chloroquine Is a Zinc Ionophore

    Yes, but probably not in a way relevant to virus treatment.

    Although chloroquine has been shown to act as a zinc ionophore, I doubt this contributes to its antiviral activity against SARS-CoV, the coronavirus that causes SARS, or SARS-CoV-2, the coronavirus that causes COVID-19.

    There are three big reasons for this:

    • The concentrations shown to affect zinc transport are far higher than those required to kill the viruses.
    • The zinc ionophore activity of chloroquine brings zinc into locations within the cell that would not be expected to kill the virus.
    • Other effects that do occur at relevant concentrations have better support.

    The zinc ionophore activity of chloroquine has only been shown for concentrations between 10-300 micromoles per liter (abbreviated uM here, a measure of the number of molecules or ions per liter). At 10 uM, it increased the transport of ionic zinc into the cell about 2.3-fold, and at 100-300 uM it increased it about 3.4-fold.

    By contrast, chloroquine’s antiviral activities against both SARS-CoV and SARS-CoV-2 begin at 0.1 uM and infection is shut down 100% at 10 uM. It kills half the virus with just over 1 uM.

    While the paper on chloroquine as a zinc ionophore didn’t show that there is no zinc ionophore activity at 0.1-9.9 uM, the fact that it has only been shown at concentrations that are 100 times the minimum concentration required to kill all the virus and nine times the concentration required to kill half the virus makes it entirely unclear whether it has any effect at all at concentrations that are actually relevant.

    The story gets worse, however.

    When chloroquine brings zinc ions into the cell, they don’t get distributed far and wide within the cell. Instead, they get stuck in a digestive organelle known as the lysosome.

    Will lysosomal zinc kill SARS-CoV or SARS-CoV-2? Probably not.

    However, in a study that

    . . .compared patients who used hydroxychloroquine and azithromycin with zinc to those who used hydroxychloroquine and azithromycin without zinc.

    411 patients took all three treatments, while 521 took the two drugs without the zinc.

    The use of zinc was not associated with any difference in length of hospital stay, duration of ventilation, or any specific settings used in ventilation.

    However, zinc was associated with a 49% lower risk of either being transferred to hospice or dying, a 44% decreased chance of requiring invasive ventilation, and a 56% increased likelihood of being discharged from the hospital and released to home care.

    Zinc sulfate treatment was started on March 25. When controlling for the date, the association with the use of ventilation was no longer statistically significant, but the association with lower hospice care or mortality and greater likelihood of going home remained significant.

    • #30
    • May 14, 2020, at 4:16 PM PDT
    • 5 likes
    • This comment has been edited.