Skip to main content


Hydroxychloroquine: Enough Already?

Update, and it’s a big one: this paper has now been retracted by the authors, who say that they are “unable to vouch for the veracity of the primary data”. None of its conclusions can be regarded as valid. Read on for historical interest only! But note that this is not the only evidence against HCQ as a therapy for coronavirus.

At this point, it’s getting hard to see how the idea of a hydroxychloroquine (or hydroxychloroquine/azithromycin) therapy for coronavirus infection can be taken seriously. I reviewed some of the recent studies here, but missed a May 11 preprint from France that had claimed benefit for the combination. No matter, though: this was just withdrawn by the authors, who say that they are revising the manuscript.

This morning brings this paper from The Lancet. Update: this paper has set off a great deal of controversy – see here. It’s a retrospective look at registered patients across 671 hospitals around the world, and it covers four patient groups: treatment with chloroquine, chloroquine plus a macrolide antibiotic (azithromycin, doxycycline), hydroxychloroquine, or hydroxychloroquine with a macrolide. All of these patients were started on these treatment regimens within 48 hours of diagnosis. The study specifically excludes those patients whose treatment started later, anyone whose therapy was started while they were on mechanical ventilation, or anyone received remdesivir as well. Early treatment in less severe patients only, in other words.

96,032 patients were registered in these hospitals with the coronavirus during the study period (December 20, 2019 to April 14, 2020); this is a large data set. The mean age of the patients was just under 54 years, 54/46 male/female. 14,888 of them were in the treatment sets defined above: 1868 got straight chloroquine, 3783 got chloroquine with a macrolide, 3016 received hydroxychloroquine by itself, and another 6221 got HCQ with a macrolide). That leaves 81,144 patients as a control group getting other standard of care. Let’s note at the start that the authors controlled for a number of confounding factors (such as age, sex, race or ethnicity, body-mass index, cardiovascular disease and risk factors, diabetes, lung disease, smoking, immunosuppressed condition, and overall disease severity). How’d it go?

Judge for yourself. The mortality in the control group was 9.3%. The mortality in the chloroquine group was 16.4%. The mortality in the chloroquine plus macrolide group was 22.2%. The mortality in the hydroxychloroquine group was 18%. And the mortality in the hydroxychloroquine plus macrolide group was 23.8%.

Let’s look at cardiac arrhythmia. The 0.3% of the control group developed new arrhythmias during their hospitalization. But 4.3% of the chloroquine treatment group did. And 6.5% of the chloroquine plus macrolide group. As did 6.1% of the hydroxychloroquine group. And 8.1% of the hydroxychlorquine plus macrolide group.

There are other interesting things about this paper (for example, it confirms earlier reports that ACE-directed therapies are associated with a survival benefit in coronavirus patients). But I’m going to leave it at this. There was no evidence whatsoever of any benefit with any of these treatment regimes. There was significant evidence of harm. Here’s how it works: when something is real, you continue to see a real signal as you collect more and better data. When something is not real, it disappears. Tell me again why anyone should be advocating such treatments. But your reasons had better stand up to 14,888 patients versus 81,144 comparators. Make it good.


464 comments on “Hydroxychloroquine: Enough Already?”

  1. Peej says:

    I have to wonder if the DSMB of large ongoing trials will need to consider stopping them for ethical reasons.

    1. Trp says:

      I know that at least one large clinical trial has paused recruitment and is re-evaluating things this weekend, I have to imagine it’s happening for many

      1. david loew says:

        There is growing evidence that this study was fraudulent from the beginning.

        This is interesting Surgisphere is the company that is responsible for collecting the data for the Lancet article on Hydroxychloroquine. The science editor for this 6 person company is Thomas Koenigsberger who died in 2018. I think this is odd. The other science editor is a digital artist whose photo was taken from her fineartamerica page. Also there appears to be no data scientists on the staff of the company in charge of collecting the data.
        Is it possible that the Lancet did no vetting of the article that they published and the companies associated with it. This is all pretty damn suspicious.

        1. Eric Penrose says:

          I agree, and according to profile searches and another ( I think it was), not only does Sapan Desai, (41, Illinois) face 3 medical malpractice lawsuits from the end of last year – as reported by, but has multiple criminal convictions. I didn’t pay to see detail – I know they’re likely not great with payment contracts.

          My main concerns with the paper itself are no availability of the software tool code or raw data and the complete lack of detail on dose especially when the average dose is stated as well above the recommended FDA upper limit.

          1. Eric Penrose says:

            Though I’m no expert on what exactly qualifies as having ‘a criminal record’, for all I know a lawsuit may qualify.

      2. Ed E says:

        So why hasn’t FDA banned it for Lupus, RA and Malaria? Does it only become dangerous with COVID19? Read the Harvey Risch paper. Outpatient use: it works (80-90% mortality reduction). Inpatient use: it’s too late. Look at Turkey’s numbers using it as the main go to drug: about 80-90% lower mortality per million and they are saying everyone else is using it too late. These contradictory results are based on when it is used and how much. It does not fight the virus but modifies the host making it more difficult for the virus to flourish. If the virus has already taken over it’s too late to modify the host. Most doctors who speak against it are big-wig hospital docs or government official docs: they don’t treat patients. Almost all who favor it are in the field.

        1. Rajiv Ishwar says:

          HCQ for patients with cor pulmonae is deadly because of cardiac Q-T wave prolongation. Many COVID-19 patients end up there because of respiratory distress. In malaria it is given once weekly because of its long long half life. Daily dosing causes accumulation because of its lon g half life of approximately 25 hours. For lupus patients where, cardiac issues are not a problem, it can used as pulse treatment to stop the damage from an overactive immune system.

          1. Daniel Baas says:

            I believe that’s the point of prescribing it within five days of the development of symptoms, to treat the patients prior to the development of ARDS, which is when most people are admitted to hospital.

            I don’t doubt the dangers of arrhythmia, but lots of drugs prolong QT interval and are regularly prescribed for far less dangerous conditions than Covid-19. For patients without arrhythmia, who aren’t taking other drugs that cause QT interval prolongation and don’t have conditions associated with torsades de pointes, the possibility of QT interval prolongation isn’t a good reason to avoid a drug that can arrest the progress of Covid-19 before ARDS occurs in my opinion. Doctors and patients have to weigh benefits and risks, but in my opinion potential benefit outweighs the potential risk in that specific circumstance.

            How absurd it is to send the newly diagnosed home with no other advice besides “come back if you have trouble breathing.”

            Also this article mentions HCQ alone and HCQ with azithromycin. HCQ with zinc and azithromycin prescribed within five days of beginning of symptoms is what has been reported as most effective.

            Interestingly, zinc is also part of the ivermectin cocktail, and at least one hospital recommended quercetin and zinc as part of a prophylactic cocktail for their employees. All zinc ionophores.

            Zinc has long been associated with inhibition of viral replication, and these drugs allow transport of zinc into cells more easily.

            Knowing how fatal covid-19 is once ARDS occurs and not having any heart conditions, I would definitely opt for a week-long course of ivermectin or HCQ + zinc if I developed symptoms of covid-19.

    2. Jeremy Gordon says:

      Hydroxychloroquine only works if combined with zinc and if given early. It allows zinc to enter cell making it alkaline and more difficult for virus to replicate. It’s not a cure but it helps immune system cope

      1. Ken S says:

        Nonsense, unless you have a real article published in a real scientific journal to back that claim up. A YouTube video is not science.

        Also, you are combining multiple alt-med conspiracy theories here (zinc as a cure-all plus the well known acidic vs basic thing that still isn’t true) so you’re not off to a good start.

        1. Unbiased says:

          Derek has not covered trials with Zinc. Here is a retrospective from NYU Grossman School of Medicine. It is a retrospective study, however, it clearly strongly suggests that the use of hydroxychloroquine as a zinc ionophore early on in the onset of the disease, has significant positive results.

          1. Anthony S.Pervan says:

            Yes. Both a Veterans Administration “Clinical Trial(?)” and this 96,000 patient “observational study” omit zinc. The “justification” or “explanation” for not including a zinc supplement is that zinc is present in our tissue. However, at best, “body stores of zinc” are at very low levels AND AT ESPECIALLY LOW LEVELS IN THE LUNGS. Hence, the need for a zinc supplement during the THREE-DRUG TREATMENT (HCQ-Antibiotic-ZINC) for Covid-19 WHICH NO AUTHORITY SEEMS TO WANT TO TEST. Why? I have no idea other than it is a low cost solution!!!!!!!!!!

        2. JoeB says:

          Dr. Anthony Cardillo, CEO of Mend Urgent Care, says that “Every patient I’ve prescribed it to has been very, very ill and within 8 to 12 hours, they were basically symptom-free.”
          Dr. Anthony Cardillo provides this explanation in his interview with ABC News. He said that combining hydroxychloroquine with zinc has been the key to the success. The hydroxychloroquine, he said, “opens the zinc channel” allowing the zinc to enter the cell, which then “blocks the replication of cellular machinery.”

          NY Dr. Vladimir Zelenko has achieved nearly 100% success while treating over 1450 patients, this as of mid-April, using the HydroxyChloroquine combination therapy, He’s getting word out about hydroxychloroquine – “anyone who blocks use of this treatment is guilty of crimes against humanity.”
          In one of his videos, Dr. Vladimir Zelenko, a board-certified family practitioner in New York, explained that it is Zinc that actually helps slows or decelerates the viral replication within the cell. But on its own, Zinc cannot penetrate the cell without the help of hydroxychloroquine. So, the work of hydroxychloroquine is to help zinc penetrate the cell.
          Dr Zelenko has continued treating patients, Calling hydroxychloroquine a potential game-changer, Dr. Zelenko maintained that his approach is to provide treatment to patients before their situation get worse so they don’t have to be admitted into the hospital and so that they don’t have to be put on ventilators.
          His out-patient treatment regimen, which costs only $12, is as follows:
          1. Hydroxychloroquine 200mg twice a day for 5 days
          2. Azithromycin 500mg once a day for 5 days
          3. Zinc sulfate 220mg once a day for 5 days

          1. David E. Young, MD says:

            Let’s see, as of Mid-April Zelenko had treated over 1,450 patients. Do you know what you are saying? You really mean that? Think about it. The epidemic hit New York in mid March. So, in a matter of 4 weeks, Zelenko saw 1,450 patients about 4 times each. One to first see the patient and order labs, one to have them return to discuss the positive covid19 test and the labs and to offer therapy, one several days later to make sure they were not worsening and a visit about 10 days later to make sure that they were recovering. So, nearly 6,000 office visits in four weeks. That’s 1,450 visits a week, or about 300 office visits a day. Do you really think that he sees 300 patients in his office a day? Are you kidding me? I have heard 700 patients over 2+ months, which might be more reasonable but still difficult. But 1,450 patients in four weeks. That is ridiculous.

        3. JoeB says:

          Dr Harvey Risch, Yale Professor of epidemiology in an American Journal of Epidemiology published review of HydroxyChloroquine and Azithromycin Titled – EARLY OUTPATIENT TREATMENT OF SYMPTOMATIC, HIGH-RISK COVID-19 PATIENTS THAT SHOULD BE RAMPED-UP IMMEDIATELY AS KEY TO THE PANDEMIC CRISIS
          …These medications need to be widely available and promoted immediately for physicians to prescribe.
          Five studies, including two controlled clinical trials, have demonstrated significant major outpatient treatment efficacy…
          The entire therapy for the HCQ/Azithromycin and Zinc costs $ 12, the Remdesivir will cost in the range of $ 5,000.00-10,000.00 for the same therapy and it’s not nearly as successful.
          Remdesivir has shown mild effectiveness in hospitalized inpatients, but no trials have been registered in outpatients. HYDROXYCHLOROQUINE + AZITHROMYCIN has been WIDELY MISREPRESENTED in both clinical reports and public media, and OUTPATIENT trials results are not expected until September. Early OUTPATIENT illness is very different than later HOSPITALIZED florid disease and the treatments differ. EVIDENCE ABOUT USE OF HYDROXYCHLOROQUINE ALONE, OR OF HYDROXYCHLOROQUINE+AZITHROMYCIN IN INPATIENTS, IS IRRELEVANT concerning efficacy of the pair in early high-risk outpatient disease. FIVE STUDIES, INCLUDING TWO CONTROLLED CLINICAL TRIALS, HAVE DEMONSTRATED SIGNIFICANT MAJOR OUTPATIENT TREATMENT EFFICACY. HYDROXYCHLOROQUINE + AZITHROMYCIN has been used as standard-of-care IN MORE THAN 300,000 OLDER ADULTS with multicomorbidities, with estimated proportion diagnosed with cardiac arrhythmias attributable to the medications 47/100,000 users, of which ESTIMATED MORTALITY IS <20%, 9/100,000 USERS, compared to the 10,000 Americans now dying each week. These medications need to be widely available and promoted immediately for physicians to prescribe.

          Dr William Grace, Oncologist and Hematologist, in an interview says people are playing politics aided by the main stream media and many academics, and that's wrong. We have got to keep the politics out of this and keep the scientists working hard, We have Remdesivir, one drug, will reduce the death rate by 11 to maybe 8%, We know that HydroxyChlorquine and Azithromycin, with or without Zinc, MASSIVELY REDUCE the risk of hospitalization and death perhaps by ORDERS OF MAGNITUDE, MAYBE AS MUCH AS 50 FOLD.

        4. Stack Pointer says:

          Unless you have a real article? Phooey.

          When essentially every “study” has been undertaken on hospitalized patients who never had a chance, good luck with that.

          I have never seen such poor quality “science” in all my life, in the heat of an absolute crisis science has been an utter failure. I hate to think it is because Trump happened to have mentioned it in a hopeful context, but people are still dying after your “real articles” have been utterly discredited.

          When people are dying and you have no treatment, give me something. If it happens to be a fifty year old drug with plain Zinc, fine. It has been clear this drug combination is both safe and effective for months. But it can’t raise people from the dead.

        5. G. Lee Aikin says:

          Here is a more complete and detailed explanation of the complementary actions of the ionophore Hydroxychloroquine and the anti viral Zinc. Several other ionophores are mentioned as well as the use of HCQ and Zinc in S. Korea which has had much success in slowing down the Covid pandemic. Korea has also used the HIV antiviral, Kaletra along with HCQ. And the articles I have read agree with Mr. Gordon that early treatment is essential; before the cytokyne storm effect destroys the lungs or the virus destroys the heme in red blood cells.

    3. Step says:

      A study by Yale yesterday says the great benefit to Hydroxy and Z-Pac, by Dr. Harvey Risch, Epidemiologist at Yale Public Health.
      Five studies, including two controlled clinical trials, have demonstrated significant major outpatient treatment efficacy. Hydroxychloroquine+azithromycin has been used as standard-of-care in more than 300,000 older adults with multicomorbidities, with estimated proportion diagnosed with cardiac arrhythmias attributable to the medications 47/100,000 users, of which estimated mortality is <20%, 9/100,000 users, compared to the 10,000 Americans now dying each week. These medications need to be widely available and promoted immediately for physicians to prescribe.


      Here are the 50 most harmful Drugs in America with Aspirin and Tylenol not even needing a prescription:

      #50. Losartan

      #49. Alprazolam

      #48. Tramadol

      #47. Venlafaxine

      #46. Sertraline

      #45. Metoprolol

      #44. Aspirin, OTC

      #43. Atenolol

      #42. Prednisone

      #41. Fluoxetine

      #40. Fentanyl

      #39. Acetaminophen, OTC

      #38. Amlodipine

      #37. Cyclosporine

      #36. Risperidone

      #35. Warfarin

      #34. Lorazepam

      #33. Valsartan

      #32. Pantoprazole

      #31. Oxycodone

      #30. Drospirenone And Ethinyl Estradiol

      #29. Citalopram

      #28. Diclofenac

      #27. Conjugated Estrogens

      #26. Olanzapine

      #25. Diazepam

      #24. Rivaroxaban

      #23. Alendronate

      #22. Clopidogrel

      #21. Furosemide

      #20. Digoxin

      #19. Spironolactone

      #18. Allopurinol

      #17. Morphine

      #16. Ondansetron

      #15. Ramipril

      #14. Rosiglitazone

      #13. Medroxyprogesterone

      #12. Lenalidomide

      #11. Methylprednisolone

      #10. Metoclopramide

      #9. Infliximab

      #8. Tacrolimus

      #7. Zoledronic Acid

      #6. Dexamethasone

      #5. Clozapine

      #4. Rituximab

      #3. Bevacizumab

      #2. Prednisolone
      #1. Cyclophosphamide


      1. VirtuvianMan says:

        Strange list, there is always a risk/benefit. Infliximab is one of greatest leaps forward in medicine (monoclonal antibodies against cytokines and ever expaning host of targets that can turn on/off parts of the immunesystem to treat autoimmune disease and cancers, so it does not take into account the amount of suffering and prolonged life/life-quality saved). Whereas the real need and benefit of the potential addictive drugs probably reflect that they are overprescribed for to long and mixed with other drugs of abuse. I do think addiction is a real medical and psychiatric disorder that needs treatment, and effective harm reduction with less addictive or non addictive. I also think the medico-legal situation is looking for someone to sue and blame.

        And if death by smoking, drinking and overeating was included in the list how would it look.

      2. loupgarous says:

        As VitruvianMan observes, that list is useless, even as an aid to context, in understanding relative toxicity of drugs. I take a few drugs on that list daily, and my physicians agree their benefit to my health far outweighs any risk to my health.

        HCQ is intended to be taken either by healthy people as a prophylactic against malaria or by people infected with a susceptible strain of <i?Plasmodium, the parasite which causes malaria. It is also, for unknown reasons, helpful to people with systemic lupus erythematosus and some people with rheumatoid arthritis. Those are its approved uses.

        On the other hand, HCQ has repeatedly been shown to be more toxic than it is helpful to COVID-19 patients or anyone else not suffering a disease for which its safety and efficacy has not been shown.

        The risk/benefit ratio for anyone not on HCQ’s list of indications who takes it falls sharply on the side of unacceptable risk of patient injury with no clear benefit. All protestations that the WHO and all the other sponsors of trials of HCQ for COVID-19 who are re-considering giving this drug to COVID-19 patients don’t know what they’re doing are, succinctly, bullshit.

        The first law of medicine is primus non nocere – “First, do no harm”. And that’s exactly what anyone prescribing, shilling for or taking HCQ off-label must consider.

      3. loupgarous says:

        Once more, with coffee:

        As VitruvianMan observes, that list is useless, even as an aid to context, in understanding relative toxicity of drugs. I take a few drugs on that list daily, and my physicians agree their benefit to my health far outweighs any risk to my health.

        HCQ is intended to be taken either by healthy people as a prophylactic against malaria or by people infected with a susceptible strain of Plasmodium, the parasite which causes malaria. It is also, for unknown reasons, helpful to people with systemic lupus erythematosus and some people with rheumatoid arthritis. Those are its FDA-approved uses.

        On the other hand, HCQ has repeatedly been shown to be more toxic than it is helpful to COVID-19 patients or anyone else not suffering a disease for which its safety and efficacy has been shown. The risk/benefit ratio for anyone not suffering a disease on HCQ’s list of indications who takes it falls sharply on the side of unacceptable risk of patient injury for no benefit.

        All protestations that the WHO and other sponsors of trials of HCQ for COVID-19 who are re-considering giving this drug to COVID-19 patients don’t know what they’re doing are, succinctly, bullshit.

        The first law of medicine is primus non nocere – “First, do no harm”. And that’s exactly what anyone prescribing, shilling for or taking HCQ off-label must consider.

      4. Stack Pointer says:

        Well, I take five of them every single day. I’m told they’re helping.

      5. David E. Young, MD says:

        If you are going to chose a chemotherapy agent as number one, why Cyclophosphomide? I mean oral Methotrexate must be at least as dangerous. What about Chlorambucil? Sunitinib? Axitinib? Pazobitib? Melphalan? The list goes on!

        1. loupgarous says:

          Clearly, it’s a risk-benefit assessment the patient’s oncologist ought to make, taking the patient’s overall health into account.

      6. loupgarous says:

        “The dose determines the poison.” Paracelsus, the father of modern pharmacology.

        Paracelsus’s point was that the only thing distinguishing a “medication” from a “poison” was how well-tolerated it is by an individual patient at a given dose. It’s why many countries require many drugs to be prescribed by a physician whose job it is to find out what the safe and effective dose for a given “prescription drug” is for an individual patient.

        HCQ is not an innocuous miracle cure for COVID-19 that we should be able to buy without a prescription. Just as we trust doctors to prescribe HCQ “off-label” for lupus erythematosus or RA (the science supports that usage, just not the FDA’s recommended indication for use), doctors should be trusted to consider using HCQ under their supervision as prophylaxis against COVID-19 if the science supports that use, and while being watchful against HCQ’s known bad side effects..

      7. Joe says:

        U should be shoved up the pipeline

    4. boffin77 says:

      Virology Journal 2005, 2:69
      Research Open Access
      Chloroquine is a potent inhibitor of SARS coronavirus infection and spread
      Martin J Vincent, Eric Bergeron, Suzanne Benjannet, Bobbie R Erickson,
      Pierre E Rollin, Thomas G Ksiazek, Nabil G Seidah and Stuart T Nichol

  2. A says:

    Did they also use Zinc? Hey, just kidding. 🙂
    Those HCQ believers will shut their eyes, put their fingers in their ears and say “lalala”.
    It puzzles me as well, but many people just believe what they want to believe nowadays. Don’t let them make you mad.

    1. colintd says:

      I was ever thus, we just hear more of the “believers” given the wonder of the Internet and (anti-)social media.

    2. anon says:

      They’ve always been around. Just look at how successful religions have been in our history.

      1. NotADoc says:

        Religion in some form seems to be wired in to humanity. Cut that circuit out at your peril.

      2. Oudeis says:

        I was once a missionary in a highly educated, scientifically advanced European country where most people were atheists. When I tried to talk religion with them, many would dismiss God as pure superstition. And then some of those same people would turn around and lecture me seriously about the benefits of homeopathic medicine or worse.

        You can see a similar phenomenon in today’s U.S., where you find anti-vaccine agitation both among working-class or middle-class conservatives and among professional-class liberals.

        There’s a lot of credulity out there, among believers as among atheists. But if you think credulity’s all there is to religious belief, I will politely suggest that you are mistaken. (And then I will stop the threadjack and leave the blog to its usual excellent discussion of very important topics.)

        1. Olandese Volante says:

          Oh, I know quite a few people who identify as atheist (of the hardcore variety: “There is no god”) who happily believe such fairy tales as Adam Smith’s “Invisible Hand” 😉

        2. David Young MD says:

          True statement

        3. loupgarous says:

          All I’d add to that is that the degree of extremism in one’s own belief system (from iron-clad atheism to some branch of belief in a God or Guiding Spirit) usually goes with one or more rejections of science as everyone else understands it (e.g., anti-vaccine fervor, Lysenkoism, various conspiracy theories, belief that fraternal organizations run the world, rabid opposition to relativistic and quantum physics and/or belief in a Flat Earth).

    3. Greg says:

      Isn’t that what a macrolide is?

      1. Greg says:

        Sorry meant: is supposed to interact with…How do you delete a comment?

    4. Kurt says:

      Sadly you and the author of this blog are doing the same thing you accuse others of doing. You choose the studies that seemingly support your view and don’t try to understand the nuances. You ignore the studies that show your view is not the entire picture. You (not the author as far as I am aware) make jokes about the opposing view when you are doing something similar.

      So what is the truth? I think if you look at the entire body of evidence available to us today you will find there is good evidence that HCQ has some preventative benefit, but we don’t know why. You will find weak evidence that it has a slight benefit in early treatment, but it may be insignificant to some or even most patients. You will find evidence that when HCQ is combined with zinc there is benefit when used with early treatment. I believe if anyone looked honestly at the entire evidence available today you would come to a similar view.

      1. Anonymous says:

        Please provide sources.

        1. Kurt says:

          (second attempt at posting)
          Here is a video that explains the theory on why HCQ with zinc may have a benefit:

          This video was posted March 17th, before any studies came out saying HCQ by itself is ineffective. In other words the idea of using HCQ and zinc was not a response to HCQ not working as some posters have suggested.

          Here another rationalization:
          In vitro it has been shown that HCQ is effective at stopping COVID19.

          In vitro it has been shown that zinc combined with an ionosphere is effective at stopping COVID19.

          In vivo it has been show that CQ (acting as an ionosphere) increases the concentration of zinc in the cell. (caveat, I don’t know if this is general to all/most cells, maybe someone can speak to this).

          Because it has been shown in vivo that CQ increases zinc concentration in the cell (see above caveat) there is a strong reason to think that the behavior of zinc stopping COVID19 in vitro would also happen in vivo.

          Here is the actual evidence:

          To the best of my knowledge there has been only one completed and published study on combining HCQ and zinc to treat COVID-19. The study was retrospective, but was of high quality, and suggests that the benefit of combining HCQ and zinc is real and significant.

          There have been many questionable studies using just HCQ with no zinc, including the one in this blog, but the following study published in the New England Journal of Medicine seems to be higher quality:

          It shows an interesting graph that suggests HCQ has a little benefit early on in treatment and a detrimental benefit later on, but overall the difference between those who took HCQ and those that did not was insignificant.

          Many of the populations susceptible to COVID19 including older people, people with hypertension, and people with diabetes are on average more zinc deficient or have more zinc metabolic issues compared to their counterparts. That being said, I have not heard of anyone trying to measure zinc levels in COVID19 patients and so this piece of evidence is interesting, but definitely speculative.
          Older people:

          There have been anecdotal reports from doctors treating COVID19 patients that HCQ without the zinc is ineffective.

          There are many anecdotal reports of good outcomes of COVID19 patients when treated with HCQ and zinc. I have not seen any negative reports.

          1. Trew says:

            I do not believe chloroquine acts as a traditional zinc ionophore through passive diffusion. The charge charge interactions and innocents nature of binding suggest therapeutically dangerous levels would need to be obtained in order to obtain Zn(II) binding.

          2. celticgirl says:

            Why dont you just start your own blog ? If you do not agree with Derek who is a professional and who knows what he is posting about then just start your own blog. Maybe you can ask Mr trump to start a blog with you !!!

          3. JP Leonard says:

            @celticgirl, we don’t need another blog, or another anecdotal report or testimonial. What we need is for the doctors – those who say HCQ+Zpack+Zn works very well for their patients – to provide datasets.
            That’s what I’m trying to do at my project /, is to reach out to doctors and clinics and ask them to show data of their Covid patients. What we need are hard numbers. I like the zinc+Hcq idea but what I’d really like is to know for a fact.
            I agree with Kurt about zinc deficiency being correlated with old age and the chronic conditions that mark 99% of the Sars Cov 2 fatalities, I wrote that up 6 weeks ago at . So we have a beautiful theory why Hcq+Zn works, but we don’t have the NUMBERS yet to prove that it DOES work.
            @Kurt is also right that calling it a religion to be a zinc fan is ditto a faith-based attitude, the pot calling the kettle black. I think most people here are all trying to use our reasoning powers to be science-based, yet being human, we are all influenced by beliefs or ideas that appeal to us.
            The reason supporters of the zinc hypothesis aren’t swayed by articles like the Lancet’s is not fanaticism. It’s that these surveys are never about zinc. From our zinc-think viewpoint their study is a huge straw man, in fact a waste of resources to look at 90,000 Hcq cases without controlling for zinc. Millions of words are being spilt about Hcq but we don’t have a dog in that fight, it isn’t the same as Hcq + zinc.
            The closest thing I’ve seen so far in terms of quant data about Hcq+Zn is the NYU study where they had 900 patients on Hcq, half of them also on zinc and half without zinc. The death rate for those on zinc was only half as high as for those without it. There is a link to it here the case fatality rate is on the last page 22/22 of the pdf. Also at the above link is a call for nationwide application of HCQ+Zpack+Zn (Zelenko’s 3-pack) which has been signed by 50 doctors.
            Time will tell, but time is ex-pen-sive on this one.
            That’s why I’m asking – if there are any doctors out there giving Zelenko’s 3-pack (Hcq+Zpack+Zn) – we could speed things up if you gentlemen could share your data. I created a data form you can download here .
            NB I should mention that one of the “Anecdoctors” Dr Rajter in Broward County Florida, says that you need to add Ivermectin to the 3-pack, and he’s planning to publish a paper on it. I believe the hospitals in his county are using his “4-pack” regimen.
            There are ten such doctors listed here . Why would 10 different doctors make up the same story and go to the media to say this treatment is working well for their patients? We need to find out what the basis is. What I don’t understand is why nobody else seems to be looking into that.

          4. Night says:

            The problem with this post is an unwillingness to formulate and speak an argument of it’s own, using links to support it rather than as the actual argument. It’s relatively easy to link a bunch of disseperate YouTube links and random studies so that no one can see the evidence in one place (indeed, this is one of the reasons why people cite YouTube videos in the first place, as making poor arguments verbally hides them better), then claim it’s all there if only people would listen.

            The NEJM study doesn’t, for example, offer the positive evidence you claim. It is at best neutral, and at worst against, noting that patients treated with HCQ were on average MORE sick after a period if time; not a positive at the start as if it mattered in some way (if it doesn’t have a big enough effect or stop a progression of the disease, that improvement has little meaning if any) followed by a negative if treated later. It just illustrated that the disease kept going regardless, and that people treated with HCQ got sicker than those not treated. I can pick a link from your post at random and find it’s not what you say it is, Kurt. That’s a very bad sign when you justify everything, even make your arguments, solely via links.

          5. Ken says:

            Hmm, Lancet versus youtube. Decisions, decisions…

          6. Diahl says:

            Kurt makes some very good points and I can only add that in many countries in Asia where I have relatives in the medical profession, there are dozens of reports of hydrochloroquine and zinc being used with success. It is the only primary early treatment in those countries. They are incredulous that the west are not doing the same.

          7. theasdgamer says:


            The reply from the anti-HC ers will be that the plural of anecdotal isn’t evidence. It’s true that well-controlled studies provide better evidence than anecdotal reports. However, in the absence of well-controlled studies (not the Lancet codswallop), anecdotal evidence is the best we have.

            The only evidence that the sun rises in the east or that water is wet is anecdotal. But I guess that isn’t real evidence. /sarcasm

          8. Kurt says:

            @Night I posted the NEJM article because I thought it did a decent job at studying hydroxchloroquine without the zinc. And I am in agreement that hydroxchloroquine without zinc appears to show little if any benefit as a treatment for COVID19. My intention was not to make a political pro hydroxychloroquine post, but to give people a better idea of the truth as far as what we know about it.

          9. Kurt says:

            I made a mistake in my understanding of this experiment:
            It was not done in vivo (in the body). That weakens my argument that there is evidence that HCQ or CQ is actually acting as an ionosphere in the human body. Certainly if anyone has more information on this please post.

          10. Trew says:

            Kurt, please see the following post.


            I do not know of one citation to the paper you link where scientist we using that methodology to study zinc homeostasis in cells.

          11. Trew says:

            Hólmsteinn Jónasson, that is the same paper Kurt linked to above. Now, please show me independent verification of the results from a different lab.

          12. theasdgamer says:

            Trew, confirmation is typically done by competing scientists in a field. Disconfirmation is an easy way to get published, barring politics.

          13. Trew says:

            Theasdgamer, ionophores are typically used to study zinc homeostasis in cells, much of which is focused on neurons. On commercial fronts, Zn(II) or Cu(II) ionophores are used as additives to paints and shampoos. While a replication of the exact experiment is unlikely to be published, a new Zn(II) ionophore would be a welcomed addition to any inorganic biochemist’s toolbox and used to study Zn(II) biochemistry at the cellular level, thus indirectly leading to conformation.

          14. Anthony S.Pervan says:

            KURT: On May 11, 2020, the NYU Grossman School of Medicine reported “anecdotal Covid-19 patient observational evidence” FULLY SUPPORTING your presentation. What happens? The Mainstream News Media basically ignores the NYU report while “eagerly and happily” reporting two NO ZINC trials that support that the “Trump touted” hydroxychloroquine does not work. Even I had no idea that Liberals are so hateful that they would prefer Covid-19 patients die than to offer them a chance at recovering.

          15. Cmdr Ralph Blowchowsky, Antedean Air Force says:

            You said:

            > In vitro it has been shown that zinc combined with an ionosphere is effective at stopping COVID19.

            Ionosphere? And you’re trying to present a (pseudo) scientific argument? Perhaps a little more attention to detail might bolster your credibility a little. Not much, mind, but a little.

        2. JC James says:

          I see that Mr Derek is at it again. This is my third post in his columns this last two months. Hopefully it is by coincidence since he is popping around when I am listing research papers from time to time. This is also my last comment since I am no troll and I cannot find any scientific information in his diatribes.

          I also have now noticed that Mr. Derek is also following Ms. Elisabeth Bik. They are both unilaterally against HCQ and both also practice cherry-picking and poor reporting/reposting. In my eyes, it looks like “science integrism” more than “science integrity” ( and I fear that with this sanitary crisis we have moved from the Social Justice Warriors to the Science Justice Warriors. One good thing, the acronym stays the same: SJW.

          I like scientific debate but one needs decent skepticism, not pure skepticism like with this new kind of SJW. I will not be surprised to see this paper withdrawn if not worse (see point 1 and 4) because it is not a preprint.

          Just to be clear, I would do the same to studies that pass peer reviews favoring or not HCQ. I stand quite neutral on preprint papers **if** represented correctly. After all, it is *the* new game and it is fine by me. But for anyone who had one to start with: do not lose your scientific mind.

          Has for one of the many daunting issues of this paper (none replicability in the first place > An email sent by a neurolog to the author of the paper

          **Request For An International Investigation On Serious Medical Faults Involved In Article Lancet**

          “In your article of Lancet, (May 22, 2020), it is perfectly established that several institutions of your registry took the criminal risk of giving the mentioned drugs in patients with cardiac arrhythmias and heart failure, while these diseases are absolute contraindications of chloroquine, hydroxychloroquine, and still more absolute contraindications for their associations with macrolides.

          Thus, 417 patients with heart failure and 520 patients with cardiac arrhythmias were put at death risk in this series, which is an intolerable enterprise of putting to death severe patients, the more as COVID 19 adds cardiac risks.”

          Has for the cherry picking from those SJW, why not explain this oddity pointed out by Pr. Raoult team (at least a bit more fair in their papers picking) ? And please, do not answer by using another computerized study like this one

          Here you have 21 references on the subject at hand and the question from the team is: Why is that that 100% of pure computerized analysis are finding HCQ inefficient even dangerous while 75% of the observational studies are finding the opposite. Quite an interesting question.


          This one just got out and I encourage anyone to read it slowly and carefully.

          -(4)- More news on the matter
          Todd Lee (Canada)

          (scientific minds at work and more issues on surface data, aka hospitals listing)

          (ethical issues)


          100 doctors and professors around the world have just posted an open letter (May 28th).

          Now, in order to bring some needed fresh air in here

          (auto-translation >

          1. JC James says:

            Gerben Wierda gave an excellent answer on (2) a two years ago and it still follows the Hubert Dreyfus critics in the 70’s.

            The most important lessons are:
            * Statistics can be very effective and worthwhile; it’s not nonsense. But …
            * Make sure your plans for analytics do not assume you can do singulars without people in control (analytics-assisted human activity, or AHA).
            * Make sure your plans take the new brittleness of the ‘new AI’ in account (again: You will need people).
            * Make sure your new statistics-based operations are ethical.
            * Make sure you plan for much more storage and compute power close to that storage.
            * Ignore everyone who talks about “cognitive computing” or “the singularity”, and in general everyone who champions new technologies without understanding their limitations. These people are peddling General Problem Solvers, and they’re going to be very expensive to listen to.


      2. Patrick says:

        Sure, but you pick *tiny*, ill-controlled or uncontrolled studies.

        No, sorry. You’re in fantasy land. The entire excitement about this drug combination was originally generated with not only a different theory of action but a different *purported benefit* than you are suggesting.

        Somewhere along the way we switched from clearance to prophylaxis, without skipping a beat. There isn’t much evidence for *either*, and a lot of evidence *against* clearance.

        Let’s wait for the biggish study on prophylaxis to come out – It will show there isn’t such an effect or I will gladly cook and eat my hat, but let’s wait! Will you say something different after that comes to pass? I certainly will if I’m wrong.

        But, anyway, it just keeps going, because, well, yeah. It just does. There’s just enough noise that people who want to believe can believe and persuade themselves they aren’t in “colloidal silver” territory, but they’re still wrong.

      3. jz78817 says:

        still clinging to the chloroquine hope at this point is little more than “I want to believe.” the fact that advocates have to continually cherry-pick little things and constantly move the goalposts means there’s no “there” there.

        can we move on please and spend time & effort on stuff which does appear to be working?

      4. Kurt says:

        Here is a video that explains the theory on why HCQ with zinc may have a benefit:
        This video was posted March 17th, before any studies came out saying HCQ by itself is ineffective. In other words the idea of using HCQ and zinc was not a response to HCQ not working as some posters have suggested.

      5. Kurt says:

        Here is my own rationalization on why I think the combination of HCQ with zinc may be effective at treating COVID-19:
        In vitro it has been shown that HCQ is effective at stopping COVID19.

        In vitro it has been shown that zinc combined with an ionosphere is effective at stopping COVID19.

        In vivo it has been show that CQ (acting as an ionosphere) increases the concentration of zinc in the cell. (caveat, I don’t know if this is general to all/most cells, maybe someone can speak to this).

        Because it has been shown in vivo that CQ increases zinc concentration in the cell (see above caveat) there is a strong reason to think that the behavior of zinc stopping COVID19 in vitro would also happen in vivo.

        1. Kurt says:

          I made a mistake in my understanding of this experiment:
          It was not done in vivo (in the body). That weakens my argument that there is evidence that HCQ or CQ is actually acting as an ionosphere in the human body. Certainly if anyone has more information on this please post.

      6. Kurt says:

        I think the combination of HCQ with zinc may be effective at treating COVID19 because:

        It has been shown in vitro that HCQ is effective at stopping COVID19. It has been shown In vitro that zinc combined with an ionosphere is effective at stopping COVID19. It has been shown in vivo that CQ (acting as an ionosphere) increases the concentration of zinc in the cell.

        Because it has been shown in vivo (inside the body) that CQ increases zinc concentration in the cell there is a strong reason to think that the behavior of zinc stopping COVID19 in vitro (outside the body) would also happen in vivo (inside the body).

        1. johnnyboy says:

          I checked that paper you cite as evidence that chloroquine increases intracellular zinc in vivo. All the experiments described in the paper are in vitro, ie. done on cells in culture. In vivo means a study done a live animal/human. Many things can be made to happen in cell cultures, which may or may not be biologically relevant in a whole organism.

          The problem with the zinc thing is that your cells all contain zinc already, as they need it to function normally. Zinc homeostasis is tightly regulated, meaning that if you take zinc orally to a level beyond what your body needs, it will either not be absorbed or be rapidly excreted. So this idea that HCQ does not work by itself but only works with added zinc looks bunk on its face, because the zinc is already there in yout tissues. Only if patients were severely zinc deficient might this hypothesis perhaps make sense; but although zinc deficiency can occur, it usually does in populations with nutritional deficiencies, eating lots of grains or plant-based materials with very little meat – definitely not the situation in western countries.

          1. theasdgamer says:

            Not all cellular zinc is the same. Zinc is typically used for cellular purposes and doesn’t float free in the cytosol. It’s typically not available to inhibit viral replication. HC increases zinc levels within endosomes. Add a virus and voila! Zinc is able to escape the endosome along with the virus and bind to the viral polymerase, preventing replication. At this point it’s just an hypothesis, but it IS based on our current understanding of cell biology.

          2. Kurt says:

            @Johnboy and others. You are correct. I made a mistake in my understanding of this experiment:
            It was not done in vivo (in the body). That does weaken my argument that HCQ or CQ is truly acting as an ionosphere in the actual human body. Instead it was only shown in cell cultures. I apologize for misleading anyone who read my reasoning on this. I wish I could edit my posts.

            I am curious to know what evidence we have that HCQ is actually acting as a zinc ionosphere in the human body beyond what we have seen in cell cultures.

      7. Kurt says:

        To the best of my knowledge there has been only one completed and published study on combining HCQ and zinc to treat COVID-19. The study was retrospective, but was of high quality, and suggests that the benefit of combining HCQ and zinc is real and significant.

      8. Kurt says:

        There have been many questionable studies using just HCQ with no zinc, including the one in this blog, but the following study published in the New England Journal of Medicine seems to be higher quality:
        It shows an interesting graph that suggests HCQ has a little benefit early on in treatment and a detrimental benefit later on, but overall the difference between those who took HCQ and those that did not was insignificant.

        1. David Young MD says:

          It’s a lousy study. Cherry picking data. I will repeat what I wrote in earlier post:

          Too many endpoints. And important endpoints were not met. You should choose the endpoints prior to looking at the data and just choose one or two endpoints, in particular, the most important endpoints (survival for example). Then do your retrospective review. (knowing that being a retrospective review already has problems). If you choose a large number of endpoints, it is almost impossible to get some association due to chance alone. Also, keep in mind… there may be another hundred hospital groups like Yale who could have published a retrospective on Hydroxychloroquine and zinc and found that there was no benefit… so they didn’t bother to report it. One study is published that looks positive and the people who read it (naturally) think that it is the only study ever done. People don’t realize that there may be many other studies or “experiences” where there is no association.

          Do the randomized study and then publish it.

          1. theasdgamer says:

            RCTs work well for chronic diseases…HBP, kidney disease, heart disease, AIDS…but how did they work out for acute diseases like SARS, MERS, H1N1, ebola? I seriously don’t know.

      9. Kurt says:

        Many of the populations susceptible to COVID19 including older people, people with hypertension, and people with diabetes are on average more zinc deficient or have more zinc metabolic issues compared to their counterparts. That being said, I have not heard of anyone trying to measure zinc levels in COVID19 patients and so this piece of evidence is interesting, but definitely speculative.
        Older people:

        1. Sophie says:

          >Many of the populations susceptible to COVID19 including […] people with diabetes […]

          I am sorry to disappoint you but this no more the case. In the lancet retrospective study, if you take time to read carefully the appendix, you will see that diabetes have an hazard ratio above one only in North America (1.305) and Europe (1.151). For South America (0.744), Africa (0.769) and Australia (0.897), diabetes is protective.

          PS: Yes, this does not make any sense. But it is actually what this study says. My post is a very bad joke but this study is even worse.

      10. WOLFRAM BLATTNER says:

        The only difference is that this article comes from the People’s Pharmacy. More than a credible source.

    5. NotADoc says:

      On the internet, nobody knows you’re an obese former pyramid power scammer. When you’re tempted to waste ten seconds arguing with one of the True Believers, consider whom you’re likely dealing with.
      Waste. Of. Time.

    6. theasdgamer says:

      I believe the best data/conclusions. The Lancet article does not measure up. Anecdotal evidence is better than the Lancet article because the disease is novel and the Lancet article mixes early buggered data with later better data.

      1. Nesprin says:

        Did you seriously just state that anecdotes are better evidence than a large, rigorously collected dataset published in the Lancet?

        1. theasdgamer says:

          Oh, you mean that article that said that its conclusions only apply in hospital settings–not to ambulatory clinics?

        2. theasdgamer says:

          I’m also skeptical that the authors could have gotten all that data ethically, analyzed it, and published in 30 days.

      2. theasdgamer says:

        I expect that the Lancet article will be withdrawn soon. From the article, HC supposedly increases the need for ventilation. That will be news to rheumatologists everywhere. More likely barotrauma due to iatrogenic treatment was the primary cause of death for covid patients early on. HC was merely along for the ride. Check out Dr. Cameron Kyle-Sidell’s youtube vids.

    7. unbiased says:

      Maybe he should actually look at studies done early with zinc…

    8. Anthony S. Pervan says:

      All the HCQ “believers” are seeking is a REAL CLINICAL TRIAL. Both the “96,000 patient Clinical Trial” and the Veterans Administration Clinical Trial OMITTED ZINC. WHEN NYU GROSSMAN SCHOOL OF MEDICINE gave patients ZINC with – got that everyone, especially Derek Lowe – it observed 44% FEWER DEATHS.


    9. Eleven says:

      A study by Yale yesterday says the great benefit to Hydroxy and Z-Pac, by Dr. Harvey Risch, Epidemiologist at Yale Public Health.
      Five studies, including two controlled clinical trials, have demonstrated significant major outpatient treatment efficacy. Hydroxychloroquine+azithromycin has been used as standard-of-care in more than 300,000 older adults with multicomorbidities, with estimated proportion diagnosed with cardiac arrhythmias attributable to the medications 47/100,000 users, of which estimated mortality is <20%, 9/100,000 users, compared to the 10,000 Americans now dying each week. These medications need to be widely available and promoted immediately for physicians to prescribe.

  3. Mark Shier says:

    “But what about zinc?!”
    I thought I’d try to get that in before the interesting posters arrive.
    Thank you for collecting this info, and for putting up with a lot of nonsense.

    1. colintd says:

      Don’t forget the zinc loaded leeches!

      Serious, Derek, thanks so much for continuing to provide a science led voice of sanity in these insane times.

      Ignore the idiots, keep up the good work!

      Thanks again.

      1. NMH says:

        If the leeches are loaded with zinc, just make sure to check their phlogistin levels. That may be an important variable.

        1. Another Guy says:

          Maybe the cure only works if you move through the aether really fast?

        2. Silverlakebodhisattva says:

          You only apply zincy leeches in cases in which the patient clearly has an imbalance of between their black bile and the phlegm….

          1. NMH says:

            ….and if Mars appears to be in retrograde motion due to its position in it’s epicycle.

    2. Felis Catus says:

      Do we need a name for the zinc proponents, Galvanists perhaps? Or Galvanistas?

      1. chiz says:


      2. Simon Auclair the Great and Terrible says:

        Galvanists is great!

      3. PB says:

        And what do you call all the sophisticates that were so easily and obviously duped by the bogus lancet study?

    3. 10 Fingers says:

      I was actually curious as to whether there was a “firm rationale” of any sort about the Zinc Effect. Following the literature chain led back to papers that indicated that the specific in vitro enzymatic effects postulated on the viral replication machinery are in the high micromolar/low millimolar range, and that the ionophore-assisted effects on cells are close to the non-specific tox limit. Never mind that HCQ or CQ do not seem to achieve the ionospheric concentrations established as sufficient when dosed in actual people (if I read it correctly).

      At the risk of opening a can of something foul in this discussion, is there any legitimate real world case to be made that this mechanism could make sense?

      1. Trew says:

        See my earlier post for a critique of chloroquine as an ionophore. To all the Zn(II) proponents, I have not seen a study using only zinc as a control. In addition, Zn(II) has long been known to inhibit many enzymes at elevated concentrations and/or increase potency of drugs with, to my knowledge, almost no success.

        1. kismet says:

          The most success zinc showed for viral diseases is as a treatment for the common cold. No, not oral zinc that ol’ snake oil; it’s high dose zinc as a lozenge. At least in that context it would reach very high local concentrations so that it might do something. Not clear this has any relevance whatsoever to COVID, though. Do we know the preferred route of entry and early stage infection? It is hard to believe zinc lozenges would help much with bona fide pneumonia…

          Hemilä, Harri. “Zinc lozenges and the common cold: a meta-analysis comparing zinc acetate and zinc gluconate, and the role of zinc dosage.” JRSM open 8.5 (2017): 2054270417694291.

          1. RA says:

            Your comment highlights something I have been wondering…are we talking enough about the optimal route of administration for potential pre-exposure prophylaxis, post-exposure prophylaxis, or early stage treatments? If the nasopharynx is where the virus initially sets up shop and replicates, is there a role for intranasal sprays, oral sprays, lozenges, etc to get high local concentrations of some agents at an early stage vs the enteral route of administration, in which one would think you would be limited in the local tissue levels you can achieve without causing systemic toxicity?

            I also wonder when it comes to immunization approaches whether there could be a role for intranasal administration, probably not as monotherapy as intranasal flu vaccine hasn’t worked well…but maybe as an adjunctive…. say you could vaccinate simultaneously with an IM injection and an intranasal spray, would that make a vaccine approach more effective on a population level given that some of the proposed vaccine candidates don’t completely eliminate infection and nasopharyngeal viral shedding, but rather reduce the risk of severe lung disease? I know there are probably many logistical reasons making that impractical, but I am curious if biologically that would potentially be more effective.

          2. Trew says:

            Interestingly, the paper was considered evidence of zinc with the common cold. The author also published the following study. Which do you believe.


          3. Nick says:

            Zn2+ Inhibits Coronavirus and Arterivirus RNA Polymerase Activity In Vitro and Zinc Ionophores Block the Replication of These Viruses in Cell Culture


          4. Trew says:

            The inhibition of enzyme activity by zinc has been known for decades. I do not know of one drug in that time frame to use zinc ionophores to increase potency of drugs in vivo. Zinc-mediated serine protease inhibitors designed at Arris pharmaceuticals is one such example.

            If humans were just cell lines, we would have a cure for just about everything that ails us. Sometimes I believe if we were mice we would have cures for half the diseases. The attrition rate for drugs successful in vitro making it into the clinic is so low that, dare I say most medicinal chemist in basic research will not work on a successful medicine.

    4. NotADoc says:

      Has to be Organic Zinc. The Big Pharma kind is loaded fetal cells

      1. Ken says:

        Fetal cells? Are you sure? I heard GMO corn.

    5. theasdgamer says:

      Ok, lol, I’ll label your side the Zinc Deniers. But seriously, zinc levels should be checked to give us more data. It’s well established that zinc levels need to be high to clear viruses. If covid undermines zinc levels, that could open the door for other viruses. Or maybe patients have low zinc levels due to diet (e.g., being old men with bad teeth who don’t eat meat).

  4. jz78817 says:

    I just read something from Carnegie Mellon where they determined ~50% of tweets promoting “Re-open America” were bots or bot-assisted.

    so I wouldn’t be surprised if a lot of the CQ/HCQ nonsense is similarly bot generated. we are being manipulated into fighting each other over everything. and it’s working frighteningly well.

    1. Tony says:

      The bots are about sewing dissent. The best thing that could happen to the world would be the sudden death of twitter. It does more harm than good (just like Hydroxychloroquine, to keep this comment on topic)

      1. Paul says:

        To be fair, if twitter would apply their own guidelines to just one high profile account, we could focus on things other than hydroxychloroquine.

        1. Charles H. says:

          Unfortunately, the Twitter guidelines explicitly exclude high profile politicians, so they *are* following their guidelines in this case.

  5. Druid says:

    Sometimes it is a good idea to give those who argue against us a ladder to climb down off the high horse, rather than climb up with them. Let’s see this as a clear result for substantial and controlled, but expensive and laborious, clinical evidence. Pressure groups can be useful but “kick and run” clinical pseudo-trials are not. There should be some senior scientists and physicians wiping egg off their faces, and some journal editors staring at the ground in shame. Apart from that, we are no further forward after wasting time, money and effort on a wild-goose chase.

  6. milkshake says:

    Derek, sorry for nitpicking, but you mentioned doxycycline as an example of macrolide antibiotic whereas doxocycline is actually from the tetracycline class. This is important distinction because the side effects, namely cardiotoxicity is what seems to be the driver in the increased mortality in the combination therapy groups.

    It just happens that doxy and other tetracyclines do not have marked cardiotoxicity. They are known for skin problems, phototoxicity, teeth enamel damage and digestive upset and also affecting CYPs (an inducer) and occasional intracranial hypertension and hepatotoxicity but no QT prolongation. In fact doxy combo with antimalarials is frequently used because it plays nice with quine-drugs

    1. Vaudaux says:

      Seeing Derek refer to doxycycline as a macrolide gave me a jolt too, so I looked at the paper. The alternative to azithromycin was actually clarithromycin (a macrolide), not doxycycline.

      1. Jim says:

        Clarithromycin is listed with a major side effect of QT prolongation. Why would this drug be indicated for a this disease?

    2. NICK says:

      Drug-induced QT interval prolongation: mechanisms and clinical management

  7. Fraud Guy says:

    Who would have thought that a serially failed businessman would point people to a product that he invested in that doesn’t work?

  8. Not a Doctor says:

    We keep bloodletting and it still isn’t working! The blood imbalance must be worse than we thought!

    This is why it’s important to publish negative results.

    1. NICK says:

      @Not a Doctor
      Donation of Blood Is Associated With Reduced Risk of Myocardial Infarction. The Kuopio Ischaemic Heart Disease Risk Factor Study

  9. psoun says:

    Derek – very interesting. Curious when Boulware’s UMN study will publish its RCT to contrast results (or pile on). I’d love to get my hands on this dataset to run some more statistics.

    One striking thing – heart issues (coronary heart disease or congestive heart failure) are noted in 16-17% of the CQ/HCQ group. On what planet would a physician prescribe CQ/HCQ to those groups, given the known heart issues with the drug? I’d be curious to re-run the results (control vs. treatment) excluding those patients from the sample. There are plenty of degrees of freedom to do that and other analyses to see if CQ/HCQ fails across the board or if there are patient segments that show any statistically significant benefit or not.

    1. Diahl says:

      Hydrochloroquine has been used for hundreds of thousands of malaria patients in Asia. The medical profession there consider it a very very safe drug. The issues of QT elongation etc only kick in at much higher doses than necessary to treat CoVID. The real question is why are people giving such dangerously high doses?

      1. Anonymous Coward says:

        Everyone out there who is using hydroxychloroquine with or without a macrolide antibiotic is taking a lead from Didier Raoult’s studies, since they’re the most prominent ones that seem to demonstrate any efficacy for HCQ. Unfortunately, as our host and many others have shown, these studies are real dumpster fires that don’t demonstrate what they say they do and have the stink of fraud about them.

      2. Anonymous Coward says:

        “The issues of QT elongation etc only kick in at much higher doses than necessary to treat CoVID. The real question is why are people giving such dangerously high doses?”

        How do you know what the necessary dose is to treat COVID-19? Do you have a peer reviewed scientific study that shows this fabulous necessary dose that should be used? Oh, right, the only “studies” out there that recommend its use are the garbage studies by Didier Raoult’s team, and that’s where the doses that most of the places that are trying to use hydroxychloroquine are based. There are known necessary doses for HCQ used as an anti-malarial that come from honest to goodness scientific studies. There are also known, necessary doses for HCQ used as treatment for lupus or rheumatoid arthritis, also based on solid scientific studies. What is becoming increasingly clear though, with all of these better studies that are coming out, is that HCQ is NOT helpful for COVID-19 at any dose.

        1. theasdgamer says:

          “Better studies”…giving antivirals late is soooo much better…covid provides a fairly long window for treatment with zinc / HC, but hospitalization is way too late for optimum prognosis.

          1. Anonymous Coward says:

            On the basis of the results of a clinical trial whose results were published in…?

          2. theasdgamer says:

            Mr. Coward,

            The evidence for the effectiveness of Zelenko’s protocol for ambulatory patients is on the basis of anecdotal reports derived from the observations of expert clinicians. Risch, who looks at a few of these, has written a paper that has been accepted for publication. Here you go…

  10. Paul says:

    A weakness of this study is that they did not include country as a covariate in their analysis. There are dramatically different prescribing patterns between countries. Also big mortality differences. If the RCTs read out in the opposite direction – this country/outcome confounding will be the most likely culprit for the difference in results.

    1. psoun says:

      There’s a lot of weakness in the statistics – it’s all at metapopulation level. I’d explore the authors to post the anonymized data online and give us social scientists a crack at it. It’s very possible more statistical analysis would confirm what the authors have but I’d like to see that.

  11. RA says:

    I find the findings on ACE inhibitors and to a lesser degree, statins, fascinating! There was an early concern that ACE inhibitors might elevate your risk with ACE2 upregulation, but the data thus far seem to suggest the protective effect seen in other viral infections may seem to hold in COVID-19.

    I wonder if there should be a strongly concerted effort to get more patients who have a clinical indication for ACE inhibitors and statins to be taking them. I also wonder if some of the health disparities we are seeing with COVID have to do with the fact that ACE inhibitors are not considered as effective antihypertensive therapy in black patients, who also have lower use of statins compared to recommendations…is this something that deserves further investigation?

    Should we go so far as to encourage people on other antihypertensives to switch to ACE inhibitors…or what further data would we need to say that with more confidence?

  12. john says:

    I agree. This is an important and well-done study. I esp. like the cautious conclusions and recognizing the limitations of the trial, esp. the potential of selection bias and the lack of applicability to treatment in an outpatient setting. The authors did try to address possible selection bias by looking at a propensity analysis and doing a tipping point analysis.

    Looking at their supplemental material, I was impressed by the consistency of the results across the different continents. There is still a possibility of selection bias, but it would have to be large to nullify their finding of a fairly large adverse effect of using HCQ or CQ.

    Looking at arrhythmia incidence, specifically, it was interesting to me in the propensity analysis, to compare the rates of arrhythmia with CQ or HCQ alone with CQ or HCQ plus a macrolide (tables are in the supplemental materials file). The concomitant use of a macrolide possibly increased the risk of arrhythmia slightly (from 4 to 6% with CQ, and from 6 to 8% with HCQ), but it did appear that use of either CQ or HCQ alone was driving the arrhythmia risk.

    After this study, it would be hard to recommend giving HCQ or CQ to seriously ill, hospitalized patients with COVID.

    1. Kurt says:

      One example of a problem with a study like this. A given hospital may be trying to use hydroxychloroquine sparingly. So they may only give it to their sicker patients. They may then end up with a large population of those who recovered on their own without needing any HCQ. This would skew the results heavily and show a higher death rate for those taking HCQ. Does this study in any way control for this?

      1. Jonathan says:

        Kurt, from the post “””Let’s note at the start that the authors controlled for a number of confounding factors (such as age, sex, race or ethnicity, body-mass index, cardiovascular disease and risk factors, diabetes, lung disease, smoking, immunosuppressed condition, and overall disease severity)”””

        “overall disease severity”

        1. Kurt says:

          The study uses data from 671 hospitals. I would imagine it is not easy to compare and control factors such as the severity of the disease between the HCQ/CQ group and the control group across so many hospitals.

          Why does this study
          give a different result and show no significant difference between HCQ and control group compared to the study in the blog? These studies come to very different conclusions which one should I trust?

      2. Alan Goldhammer says:

        In our local hospital which is a branch of a major US med school, HCQ was the standard of therapy from the start of the outbreak in our area. I suspect this was the case for a number of others as well.

      3. John says:

        Kurt, I think the possibility of a selection bias remains. One common error that naive readers of studies make is, when they see a study with 90,000 patients, they think it must be more valid than a study with 900 patients. This is not necessarily so. The same selection bias can exist with the 90K patients as with 900 or even 90 patients. People go through all sorts of ‘adjustments’ as the authors of this study did, and more recently, making adjustments using propensity score analysis. However, if the physicians in charge were deciding to treat more severe patients preferentially with CQ or HCQ, with or without a macrolide antibiotic, unadjusted for selection bias may still be a factor. For example, in the VA ‘study’, there was at least one indication that patients treated with HCQ were more severely ill, in terms of having a lower white blood cell count. Having said this, the authors or this study are well aware of the selection bias problem, and did just about everything humanly possible to minimize it. And the magnitude of the increase in mortality, as well as the increased arrhythmia risk found is not trivial. One of the downsides of some studies with 90,000 patients is, that there is a chance of finding a “20% increase in risk” of something when the baseline risk is only 1% or so, and so moving from 1.0 to 1.2% is not a big deal. But the increase in mortality risk in this study was a big deal and is clinically important.

        Still, I don’t think this study should dampen enthusiasm for testing HCQ for early treatment in an outpatient setting or post-exposure prevention. Here the risk of arrhythmia is likely to be similar to that seen in treating lupus patients or patients with rheumatoid arthritis (essentially nil). And those who have advocated for use of HCQ to treate COVID emphasize that HCQ may work only when given within a few days of onset of symptoms. Plus there is the zinc argument. There is one potential safety argument against use of HCQ early to treat COVID-19. It may work to reduce severity of symptoms and harmful tissue effect, and if the patient recovers without requiring hospitalization, fine; no safety issue there. However, in those few patients with COVID-19 and taking HCQ who will require hospitalization, even if the HCQ is stopped at time of admission, the medication has an extraordinarily long half-life, so prehospitalization use will result in some amount of HCQ remaining on board during a hospitalization. This may theoretically put the patient at risk of a poor outcome or arrhythmia, when HCQ is onboard along with the panoply of additional stressors that seriously ill, hospitalized patients often encounter.

      4. Spencer Stang says:

        You are correct. In fact, the reason that everybody keeps saying that we need RCTs is that attempting to control for all factors statistically is near impossible without randomization. Even eyeballing the data you can see that the control group was younger, had fewer comorbidities, and was less sick. Nonetheless, you nailed the most likely source of bias, it’s almost a given that the patients treated, on average, were sicker than the patients not treated. This control group is basically meaningless. Actually, it’s worse than meaningless because it gives the false impression that it has been corrected in a way that it can be trusted.

        1. Tony M says:

          Question – The data included patients hospitalised between Dec 2019 and April 14, 2020. Most of the data comes from USA, Brazil, Australia, France, Spain, Italy and UK. I thought most, if not all, of these countries had restrictions on the use of these drugs to patients in clinical trials and/or compassionate use in severe cases. To the extent that doctors adhered to these restrictionsand administered these drugs to the more severe cases, wouldn’t you expect to see a relationship showing increased risk of mortality and/or ventilation?

      5. Ken says:

        You really should contact the Lancet and get registered as a reviewer, so that you can catch these things before the articles are published.

  13. JL says:

    I’m here. And not enough already. Yes Zinc. Maybe that’s the tungsten missing from some dim bulbs out there. Zinc is the actual point here, right?

    Consider this like a peer review. Many of your peers, although you spit on them with your contempt, are saying Your Results Are Not Valid because your tests do not include administering zinc with the Zinc Ionophor, and it’s intra-cellular zinc that has been shown to stop replication in vitro. Your “experiments” do not replicate the in vitro in vivo.

    This is a Valid Argument.

    1. chiz says:

      According to the sermo surveys – which appear to be self-selecting, admittedly – about 11% of patients hospitalized with covid19 are being treated with Zinc. If it cured them in 4-5 days as Zelenko claimed then I think its safe to say we would have heard about it by now – from the patients, from their relieved relatives, from their doctors, from the hospital administrators, from the health ministers. Wow, they would be saying, this stuff is amazing. But they’re not.

      1. Spencer Stang says:

        Treatment after hospitalization is too late for Zelenko type results. This has been emphasized repeatedly and yet one hospital study after another comes out showing that HC isn’t effective.

        Second, we are getting the reaction you speak of from doctors and patients around the world. I literally read them every day. You’re looking in the wrong place (i.e., hospitals or CNN).

  14. JL says:

    HCQ has been given to hundreds of millions over decades. Over all that time there has been no study or report that concluded with a single fatality due to prescribed HCQ, other than overdose. Why all the sudden has HCQ taken on an evil Orange glow? Although I am also one of those whose least favorite color now is Orange, I am wondering if perhaps its the Orange chromatophobia should be studied. Since HCQ was like M&Ms before they got rebranded Orange.

    1. Miles says:

      Nooooooo, don’t say orange, it will set the Curcurminophiles chattering…

    2. milkshake says:

      Because HCQ is hyped by quacks for very seriously ill patients, many of which end up with respiratory failure and pulmonary hypertension leading to cardiac failure. The combo with macrolide antibiotics exacerbates the QT prolongation problem even more.

      Use of chloroquine and HCQ started as a reasonable hypotesis, which unfortunately did not pan out. In the meantime, the politicians in their typical wishful thinking latched on it as a hope because it is a very cheap drug with a manageable safety profile in patients that do not have heart condition. if it had worked, it would have been potentially useful as a preventive medicine. Except that there is not even a hint of efficacy, any multitude of evidence of harm in the coronavirus patients. And there are always idiots who hope that there must be something – something to stop the plague, who have no real understanding how drug development works. And then there are hucksters and charlatans and mountebanks. One of them even works in the Oval Office

      1. NICK says:

        If you have adequate potassium = very low chance of QT prolongation

    3. NMH says:

      Taking HCQ without a viral infection maybe a quite different context. We’ve learned that the SARS-2 virus potentiates clotting in the blood, so it could be HCQ would make the clotting worse. In other words, you need something else (the virus) to get the bad affect that kills people. If that is not there, no problem.

      1. psoun says:

        Yes, except:

        Seems there is a bit of evidence that HCQ actually *reduces* clotting.

        The dataset that the Lancet authors have is extremely rich – can we unpack it more and try to glean more information on patient cohorts that are especially prone to poor or good HCQ outcomes?

        1. NMH says:

          Again, this was a study in vitro with a purified system and not done with virally infected blood, and the references for a anti-thrombotic affect are presumably on otherwise healthy donors that did not have septicemia . Viral infection, and the blood septicemia that comes with it, may be be enough to change things.

    4. MTK says:

      It has not been given to anyone with COVID-19 until the last six months or so.

      Is it not possible that COVID-19 is a contraincidaction for HCQ?

      That’s the one thing I do not understand with the whole “it’s been used for RA and lupus for decades so it’s safe” argument. That is no guarantor that the drug will be safe for COVID-19, or other indications for that matter.

      There are plenty of examples of drug-disease interactions which can increase the risk of otherwise “safe” drugs with certain patient populations

    5. jz78817 says:

      even I know of the phenomenon of a “drug-disease interaction.” a drug that’s safe and effective to treat one disease can be dangerous when tried for another.

      Look at aspirin. taken daily by billions of people for all sorts of ailments, so it’s pretty damn safe. EXCEPT! don’t give it to a child who is suffering or recovering from a viral disease like the flu or chicken pox, else you risk causing Reye Syndrome.


      and I know, I know, HCQ/zinc kills the virus in vitro. You know what else kills the virus in vitro? A blowtorch. But that doesn’t mean you should recommend setting people on fire as a cure.

        1. Ken says:

          Also which is especially important when people start talking about finding subsets of the patient population where HCQ (or zinc or whatever) is statistically effective.

    6. You hit the nail on the head. If you want to kill HCQ, you do studies that use overdoses.
      If HCQ is so bad, why did the FDA approve it even for malaria?

      Lupus patient take HCQ for life. They are not dropping dead in the streets.
      With $43 billion corrupting the “medical scientific consensus”, you cannot trust them.

      Immunological mechanisms explaining the role of IgE, mast cells, histamine, elevating ferritin, IL-6, D-dimer, VEGF levels in COVID-19 and dengue, potential treatments such as mast cell stabilizers, antihistamines, Vitamin C, hydroxychloroquine, ivermectin and azithromycin

      May be HCQ is not great but with corrupted science, we will never know the real answer.

      1. Charles H. says:

        You are really reaching. Really.

        HCQ isn’t *that* bad, except in large doses or within a particular patient subpopulation. Quinine is better than malaria, but that doesn’t make it great when it’s not helping anything.

        Claims based around studies in a petri dish are interesting rather than convincing. They can point to places where it’s useful to look more deeply, and they’re relatively cheap to do. But don’t use them as an argument for how to treat patients.

        FWIW, given current info I, and not medical professional, have decided to treat myself with a good quality multi-vitamin plus minerals pill every day, plus a weak vitamin D supplement. This is a bit dubious as it *could* lead to an overdose of vitamin D, but I occasionally forget, so perhaps it balances out. And I tend to spend all my time indoors and wear long sleeve shirts.

        It’s plausible that low levels of zinc are a problem, though it hasn’t been shown. But high levels are also a problem. Similarly with vitamin D, though the evidence is a bit stronger. But for various quinine derivatives….if tonic water still contained quinine, I might switch my drinks to gin and tonic.

  15. Mostapha Benhenda says:

    The study is not reproducible, they didn’t publish their data. There is a lot of flexibility in the parameters.

    1. D P says:

      LOL, did you just look at a list of potential problems with studies and pick three without thinking? There is plenty of money and patients to support another study of this kind. They didn’t publish their data? 99% of studies don’t publish their data, doesn’t make any of that work false. They may still make it available. I suspect that the flexibility of parameters is something that can’t be avoided when working with a study that spans multiple countries and thousands of patients and was factored in to the analysis, thus not a critical flaw.

  16. Lane Simonian says:

    Assuming that zinc is effective against coronaviruses (and that still is an assumption that must be proven), what would make hydroxycholorquine/chloroquine better/safer/more effective than any other zinc ionophores?

    1. David Young MD says:

      Too many endpoints. And important endpoints were not met. You should choose the endpoints prior to looking at the data and just choose one or two endpoints, in particular, the most important endpoints (survival for example). Then do your retrospective review. (knowing that being a retrospective review already has problems). If you choose a large number of endpoints, it is almost impossible to get some association due to chance alone. Also, keep in mind… there may be another hundred hospital groups like Yale who could have published a retrospective on Hydroxychloroquine and zinc and found that there was no benefit… so they didn’t bother to report it. One study is published that looks positive and the people who read it (naturally) think that it is the only study ever done. People don’t realize that there may be many other studies or “experiences” where there is no association.

      Do the randomized study and then publish it.

  17. Trew says:

    Several Articles are starting to make there rounds regarding doxycycline. Preliminary results and proposed clinical studies, some with chloroquine and derivatives, are discussed.

    Many of these links are opinion based and/or computational, others are very small trials and should be taken with a “dead sea” worth of salt. Just something to keep an eye on.

  18. Spencer Stang says:

    This study adds nothing to the understanding of the primary hypothesis. The hypothesis is that a combo of HC+Az+Zinc given early (far before hospitalization) will lead to a significant improvement in survival. The best evidence for that hypothesis is that doctors worldwide, that follow a version of this protocol, have a case fatality rate of about 0.5% while the worldwide average is 6.5%. Countries worldwide that follow an HC protocol have a case fatality rate of 2.65% vs. 9.83% for negative control countries that don’t allow early treatment. Countries in the middle that use HC treatment on a case-by-case or doctor-by-doctor basis (like the U.S.) are generally in the middle of this range. In combo with in-vitro studies and tremendous correlational evidence for prophylactic efficacy (malaria countries/lupus patients/India police and healthcare) it is silly to downplay early HC treatment as if the late case, poorly controlled studies have addressed the question of interest (they have not). Links to source data . . .

    Oh yeah, they also forgot about zinc and the control group was younger and less sick with fewer comorbidities (which I would guess is a big part of the reason that they weren’t treated in the first place). You should be the one telling us all of the above, not the other way around.

    1. Doubtful says:

      Ah yes, the good old google doc source data. we can trust this 100% right?

    2. Doubtful says:

      Oh Look, twitter pages and Dr. Oz and non scientific news sites are all cited on this doc. Excellent. Can I post something on twitter and throw some fake data into the spreadsheet?

      1. Spencer Stang says:

        Your welcome to suggest a correction if you see something wrong. If a doctor publicly claims to have treated X number of patients with X deaths it gets added to the spreadsheet. The beauty of having sources listed is you can drop any sources you don’t like and see what it does to the conclusion. Here’s a challenge for you, try dropping enough sources to change the conclusion. To change the conclusion, you basically have to say that almost all of these docs are lying. Raoult is a liar, Zelenko is a liar, Stephen Smith is a liar, etc. That sounds highly implausible to me but it is possible that only successful docs are reporting results. I can’t find any doc IN THE WORLD who has treated 50+ patients using the HCZZ protocol early without above average success. If you can find this result, please pass it along.

        BTW–if you want to be snarky, I’ll snark back just cause that’s what you deserve. If you want to try to solve a problem, I’ll work night and day to make that happen and add any data sources you can find that are publicly reported and potentially verifiable. Yes, even a twitter report that links to a newspaper article or pre-print or anything that looks like it would be a pain to fake.

    3. Seebs says:

      “The” primary hypothesis? I don’t recall “zinc” being mentioned in Raoult’s paper, only in Zelenko’s. So is it necessary, or not? If zinc is necessary, then why do we have a paper claiming to show such great effectiveness without it? Doesn’t that paper show that zinc ISN’T necessary?

      It seems to me that “the” primary hypothesis is subject to rapid change; I’ve seen it claimed that HCQ (or HCQ plus something) is effective specifically for severe cases, or only for early cases, or only as a prophylactic, and each time one of them is shown not to have any clinically-reproducible results, there’s a response explaining that it only works in the other cases. But when those get studied, and the results are bad, the same thing happens.

      It’s becoming increasingly difficult to believe that this is even being offered in good faith, at this point.

      1. Kurt says:

        I first learned about the HCQ with zinc treatment indirectly through the following video which was posted on March 17th. I have not found an earlier reference on the internet for this idea as applied to COVID-19.

        Dr. Zelenko started his protocol on March 18th. Did he get his idea from the video?

        The HCQ treatment was started by China and/or South Korea at an earlier date and I don’t know the details on how this came about.

        The idea of using zinc with an ionosphere to inhibit an RNA virus can be found in the following study from the year 2010. In this study the ionosphere is pyrithione and not HCQ.

        Chloroquine was shown to be a ionsphere for cells in the body in the following study from the year 2014.

        So it does seem there are two independent lines of theory around these treatments. Which one was first depends on how you look at it.

        1. drsnowboard says:

          ionophore. It’s ionophore. If we can’t spellcheck our autocorrected text, what else can’t we check?

        2. 10 Fingers says:

          The pubmed link you cite here shows that the direct in vitro effect on the purified RNA-dependent RNA polymerase part of replication machinery that is at the core of the hypothesis only happens as concentrations approach the millimolar range, with >95% inhibition indicated at 6mM. The closer the experiments get to testing the hypothesis at the molecular level, the less compelling their data becomes.

          In general, much of the data associated with this hypothesis appears to rely on concentrations of either zinc or HCQ that cannot be achieved, when dosed in people, at high enough levels to achieve their stated function.

        3. loupgarous says:

          “The idea of using zinc with an ionosphere to inhibit an RNA virus can be found in the following study from the year 2010. In this study the ionosphere is pyrithione and not HCQ. Chloroquine was shown to be a ionsphere for cells in the body in the following study from the year 2014. …”

          Is anyone else getting flashbacks from the movie “Dinner with Schmucks”?

  19. Erik Dienemann says:

    Thanks, as always for your cogent analysis, Derek. Elsewhere, someone said to me that the fix was in to which I replied that they essentially include everyone in a bunch of hospitals who was PCR-positive for COVID and started HCQ treatment within 48 hours of admission (so as not to bias the HCQ group with patients who were started later and potentially more seriously ill) and compared those people to all others who were admitted and not treated with HCQ, so “bias” would be really hard to achieve. This also means it was a trial with at most moderate symptoms, since they all started treatment within 48 hours of admission, so it’s not a case of HCQ doesn’t work in severely ill patients.

    Been saying for 2 months that given the huge numbers being treated with HCQ, if this were a cure or even moderately effective, we’d absolutely know about it by now. Nope. This is the death knell for HCQ whether people like it or not. In fact, I’d go so far as to say we should probably stop any clinical trials using HCQ post-admission to a hospital, as we shouldn’t be subjecting anyone to roughly a 1.3-1.5X greater mortality rate (adjusted) treatment. I’d only continue HCQ trials pre-hospitalization at this point and grudgingly so.

    1. Spencer Stang says:

      How do you explain the dramatic difference in worldwide death rates between countries that embrace early HC treatment vs countries that don’t (under 3% vs 9+%)?

      How do you explain the dramatic difference in case fatality rates for doctors using HC treatment early vs worldwide case fatality (0.5% vs 6.5%)?

      How do you explain the dramatic difference in deaths per million in favor of countries that have a high prevalence of people taking HC for malaria?

      How do you explain the dramatic difference in likelihood of getting COVID 19 between lupus patients (taking HC) vs everybody else? Non-lupus patients are 50x+ more likely to get COVID 19 vs lupus patients.

      How do you explain why police in India that are taking HC prophylactically are less likely to die than police who are not taking it?

      Say what you want about wanting you gold plated RCT (which I want too), but don’t say that there’s no evidence that early HC treatment works. Science is more than what you find in journals.

      1. Stork says:

        Last year we had many storks over here and many babies were born so good evidence that these babies were delivered by storks as we know already for ages

        1. Christopher Andrus says:

          You’re a fucking moron, Stork! Your mocking comparison dismisses legitimate findings. You are probably anti-HCQ because you hate President Trump. Well, that’s no basis for analyzing medical issues.

          1. drsnowboard says:

            Really made a cogent argument there, I cannot be but persuaded by your depth of analysis and argument.

      2. Somewhere in the Rest of the World says:

        How do you explain HQ, other than a country being torn apart by a preventable situation desperately pointing at anything other than the actual problem. Years of anti-intellectual rhetoric have come home to roost. To the innocent, sorry.

      3. Med(iocre) Chemist says:

        People bring up the lupus thing like it’s the smoking gun and I just have to ask: where is this claim coming from? There are anecdotal reports, sure, but no studies that I can find that show SLE patients taking HCQ are immune to COVID and that SLE patients taking something else are not immune (since you would have to assume that people with lupus are going to be very risk-averse in these times).

      4. Athaic says:


        I think all your claims are fabrications or embellishments.
        Or comparing apples to oranges.

        “case fatality rates for doctors using HC treatment early vs worldwide case fatality”
        Local vs worldwide. Sure, no way there could be other factors in play than HCQ.

        1. Spencer Stang says:


          Fabrications!? You’re a piece of shit to make accusations based on . . . nothing.

          Sources linked. You can argue all you want about what the discrepancies mean or even whether the data from Worldometer, et al has any meaning, but “fabrications”? That seriously crosses a line.

      5. Lewis says:

        Maybe I’m confused, but isn’t France one of the leading countries that pushed HC? Their deaths to positive cases is awful. If it’s so great why isn’t France flaunting the numbers? And didn’t they cancel the ‘HC for all’ mantra and switch it over to hospital use only???

        (Not trying to be snarky – this doesn’t make sense to me.)

        1. Spencer Stang says:


          The question about France is a great question. France, was/is strongly split on HC, kind of like the U.S. I’ll copy a link below that sums it up nicely although you may have to translate the graphs (unless you know French). The bottom line is that the HC friendly (Raoult et al) part of France (Marseille) getting HC treatment has a 0.5% fatality rate compared to 21.6% nationwide. More testing in Marseille may explain some of that discrepancy (the denominator issue), but any thoughtful person looking at the numbers has to acknowledge that it’s a strong argument in favor of early HC treatment.

          Note that more recently, the rest of France (not surprisingly) is becoming more HC friendly, so these numbers are about to get messier to interpret, but hopefully better for France overall.

          1. Lewis says:

            The problem is it was reported HC prescriptions in Paris were very high. (I believe Forbes and Bloomberg). Paris’ look maybe better than average in France, but they are still terrible. A big problem is data access and accurate reporting. Is France actually reporting HC usage? It seemed to be the talk of the town, then it went silent. over 2 months since the original HC paper they used as justification, and no comprehensive retrospective. I don’t get that. The researchers usually want to share when they hit a home run – why hasn’t that lab published a follow up?

            I think alot of eyes are on France. If HC isn’t good, they need to report that. If it is good, they need to report that. The bottom line is that group needs to report. It’s been way too long. The country went down the HC rabbit hole… let the world know the result. Many lives could be helped either way.

        2. WST says:

          Only minority of hospitals in France use HCQ and/or AZT, against official French health authorities recommendations. Some in Paris ( CHU de Garches) and south- east Marseilles, Nice etc.
          The mortality at the IHU hospital in Marseilles is rather 2.6% (18 deaths and 692 hospitalized patients), while 3,308 were treated with HCQ.

          IHU information is very interesting but not easy to find

          open this link, then click on the graphs (one page down) and clock on the right arrow.
          All hospitals in Marseilles, all treatments, mortality 3,17% , 4882 patients, 155 deaths, still much better then the French hospitals’ lean of 7.6% …IHU did also 7800 ECGs.

          I know it’s a lousy argument, but wouldn’t you like to be admitted to IHU if you ever had the bad luck with this virus ?

          Italian, large scale statistics are very interesting, the active cases was still growing until roughly 20 April. But already ICU beds were freed up, roughly hundred a day since first week of April. Then hospital beds started to get freed-up even with active cases were still increasing or stabilised. HCQ was authorised for prescription by hospital doctors on 17/3. Standard treatment was 400mh HCQ a day, with addition of potassium and magnesium, QT limit for administering the treatment was 440 ms for men and 460 ms for women.
          Patients with mild symptoms were treated and isolated at home thus the bulk of patients moved from hospital to homes.
          Maybe there was some other magic at work that suddenly covid changed character.

          1. Lewis says:

            Thanks Spencer and WST,

            The problem is even given the rates from south France, there are states in the US with similar (or better rates). We are just conjecturing…. why isn’t there a systematic retrospective done by medical researchers. The rates across the US seem pretty diverse, given that diversity it feels like there are too many variables to stare at broad trends and try to infer something. Given the US President’s continued hype of the drug, I think medical folks in the US need some clear messaging regarding HC. Obviously other parts of the world would benefit from a clear report as well. Why hasn’t Raoult’s groups published something? It feels like eyes are on him right now.

  20. Nada Nemo says:

    Not terribly pertinent to this blog, but isn’t there a psychological analog for the financier’s “sunk cost fallacy,” wherein people keep spending good money after bad, because they don’t want to acknowledge that they made a bad decision and take their losses?

    It seems that something like this is going on here. For some people, the bad decision wasn’t to support hydroxychloroquine, it was to support leaders who spout snake oil. For this latter group, vocally supporting a drug that is not only useless but potentially dangerous has become a loyalty marker for their membership in what’s an increasingly toxic relationship with their increasingly abusive leader. To do otherwise would be to admit that they made a colossal mistake in supporting that leader in the first place. Unfortunately, it may appear to them that continuing to be abused (and to be abusive in turn) is less painful than pulling out of the abusive relationship and detoxing from it.

    Unfortunately, this is a problem of psychology and politics, so it’s not really something that we can address here, except to continue to point out that there’s no benefit from hydroxychloroquine for Covid-19, and hope this helps people realize that they don’t need to stay and keep being asked to abuse themselves to show their loyalty.

    1. Derek Lowe says:

      It has been increasingly obvious that the Marseilles data are not controlled and are, in fact, nearly uninterpretable. I have referred to these numbers several times in previous posts on hydroxychloroquine.

    2. Ulrich Lingner says:

      The problem is with the 18 deaths after 3 days of treatment. They simply exclude the patients that die or end in the ICU within the first 3 days. This is the case with the Gautret study – 6 patients from 20 excluded, one of which died, three landed in the ICU, and also with the withdrawn preprint from May 11, where 9 patients from 57 ended in the ICU or died and were removed from the study.

  21. Ulrich Lingner says:

    Hey! What about the successful study published May 1 in medRxiv. by Dr. Bo Yu? Also a retrospective look, where HCQ was used for another purpose with critical patients.
    And the one published April 19 by Amit N. Patel, one of the signers of the Lancet study, about the success whit Ivermectin?

    1. Derek Lowe says:

      Your first reference is covered in this blog post, in detail:

      And the second one is in the blog post on Ivermectin, at the very end:

      Anything else I can help you out with?

  22. Kurt says:

    Another viewpoint is that there is potentially a good treatment (hydroxychloroquine and zinc) that has shown to be effective at saving lives but is being buried because of politics. Many want to say because hydroxychloroquine has been shown to not work that adding zinc to it won’t help. However they have not tried to understand the theory behind it and they ignore any studies on it. Why is this?

    If someone can give me a scientific or evidenced based reason on why hydroxychloroquine with zinc does not work, I would be interested in hearing it. I would rather learn the truth than be on the winning side of an argument.

    1. Seebs says:

      First: There are millions and millions of chemicals. If we’re spending time investigating this one, that comes directly out of time spent investigating others.

      Second: The story changes constantly. The original claim didn’t include zinc. The new claim requires zinc. But if that’s the case, then the original claim was *completely fraudulent*, and that would leave us at “no actual reason to think this works”. So why should we be investigating it? If your story changes that fast, and contradicts the previous story, *none* of them are credible.

      Third: On the scale of a trial this large, if HCQ+zinc worked, there would have been an observable effect because enough of the patients *were on zinc supplements for some other reason, already*. Or just taking it anyway. I know one of the things I took when I started feeling a bit under the weather had zinc in it. So if HCQ+zinc had an effect anywhere close to the scale you imagine, a plain HCQ trial would have shown a benefit in *some* patients and it would have been possible to drill down to find out why it was helping them. But it didn’t.

      So, the question is: Do we have *any* actual coherent evidence suggesting that this combination works? No. But I know what will happen. If someone goes and does a large, randomized, controlled trial of HCQ+zinc, and shows no effect… You’ll be right back telling us that it’s something else. Maybe it needs to be given late, now. Maybe it should be given early. Maybe it’s only a prophylactic effect. Maybe it’s zinc plus… vitamin D! Wait, no. Vitamin B12. We haven’t tried *that* yet.

      But you’ll never, ever, admit that it maybe just doesn’t actually work.

      1. Charles H. says:

        B12 is useful, and there’s a significant population that is low in B12. Of course, that’s not a claim that it’s useful against COVID, but it *is* useful. More elderly people have a harder time absorbing it from the diet, and many diets are low in B12 anyway.

        Similar comments apply to Zinc. Except that too much Zinc damages the immune system. Whoops. (B12 seems to tolerate high doses a lot better.)

      2. M says:

        Yes, the reason to think HCQ might have worked in humans in a clinical setting is these early observations that suggested a strong effect. But strong signals are easy to confirm! In point of fact the early observations were seriously flawed. It stops being a case of the truth being “somewhere in the middle”; the studies in such a case have no evidentiary value.

        (The analogy is if you have an eyewitness saying they saw me shoot someone, but it turns out I was in a different state, you don’t say “Well, sure that’s wrong but you must have been involved some other way! Eyewitness evidence is really convincing and they wouldn’t be completely wrong!” The relevance of this analogy to studies can in fact be described mathematically if you look into errors caused by low powered hypothesis testing.)

        The pattern of only seeing an effect when you do small studies or proxy measurements is completely consistent with a bad hypothesis.

        Attempting to save the hypothesis after you have this data on ~100k patients is at the point where you are keeping patients from both better treatments and potentially useful clinical trials.

        I’d add that most people who’ve been doing this a while have probably had a point in our careers where we strongly believed an attractive hypothesis and early data, convinced ourselves to ignore the ambiguous follow up data then watched the treatment die in phase II or III. People doing armchair development haven’t experienced this and can’t understand how in vitro and some follow up clinical data could be so irrelevant so they grasp for other hypotheses like “Zinc!” or “You are all politically motivated!” This is just what happens to preliminary data in the field. It gets chewed up and spit out.

      3. Erik Dienemann says:

        Great post. Just posted this elsewhere in response to someone who was saying that the observation that the control group had 7.7% intubated in the Lancet study vs. his number of ~20% intubated of those who enter hospitals, in general must have meant that the study was flawed, or worse, fraudulent. Below is my response.

        There’s a simpler explanation: HCQ/CQ are dangerous and cause greater side effects (particularly much higher rates of ventricular arrhythmias) and mortality and combined with the very high HCQ/CQ treatment rate since late March (after the hype started), this is why the overall rates on vents in NYC/US (and likely everywhere) are greater than they would be if HCQ/CQ weren’t being used.

        If we use NYC as a surrogate for the Lancet study (it has had the most patients and most of the patients in the Lancet study were from the US, meaning it’s very likely a sizable proportion came from NYC), then the percentage of hospitalized patients intubated is approximately 17% (22% to ICU and 79% of those on vents), as per the WebMD link.

        In addition, a decent estimate of the percentage of NYC hospitalized patients on HCQ/CQ is about 82%, based on the JAMA study in NYC, where out of 1438 randomly selected patients, 735 (51.1%) received HCQ/AZ, 271 (18.8%) received HCQ alone, 211 (14.7%) received AZ alone, and 221 (15.4%) received neither drug. So, if one takes out the AZ-only data, HCQ treated patients are 82% of the total.

        However, it should be noted that the JAMA NYC study was conducted on patients who were hospitalized between 4/-9-4/27, which was probably the height of HCQ use, given Trump’s numerous statements hawking HCQ/AZ from around 3/20-4/15 and before many papers started coming out in mid/late April questioning the efficacy and safety of HCQ.

        In comparison, the Lancet study had patients hospitalized from January through early April (with all patients discharged/dead by 4/21), meaning a much greater percentage were treated before the HCQ hype, so it’s not that surprising that this study had a much lower % on HCQ/CQ (but I wouldn’t have thought it would be only 15%, but that shouldn’t really matter).

        If one assumes the Lancet study is “correct” that 20.6% of HCQ/CQ patients get intubated and 7.7% of non-HCQ/CQ patients get intubated and we use the JAMA study ratio of 82/18 HCQ+CQ to non-HCQ/CQ for NYC patients, in general, then we’d expect to see 18.3% of overall patients becoming intubated in NYC hospitals, assuming they all have 82/18 ratios of HCQ/CQ to non-HCQ/CQ patients in their hospitals, which is not far from the 17% intubated number in NYC from the WebMD data.

        The point of this analysis is not to unequivocally say that the Lancet study is 100% perfectly correct – it’s to say that it’s plausible it’s generally correct, that HCQ/CQ offer no efficacy advantages and probably are truly associated with greater ventricular arrhythmia, intubation and death.

        Last point: if the NYC HCQ/CQ treatment prevalence data of >80% is correct for the US and probably many other countries (didn’t look at Europe, but we know usage went up everywhere), or even if it’s just 50-60%, then without even doing any “studies” it’s not hard to conclude that HCQ/CQ offer no mortality reduction benefit, given that US case mortality rates steadily climbed from 2.9% as of 4/1 (when all deaths would likely have been from cases before HCQ use skyrocketed, given the 2-4 week delay from infection to death) to 5.8% as of 5/1.

        Surely, if 40, 50, or even 80% of patients were now being treated with HCQ, if it offered a mortality benefit, we would not have seen the CFR double would we? This is what I’ve been saying all along and why I think you’re actually not seeing the big picture here. Have at your prophylaxis arguments, but I don’t think there’s any argument you’ll be able to make to make me think that HCQ/CQ is helping hospitalized patients – on the contrary, I think the Lancet and other publications have it right and we should stop using HCQ/CQ in all hospital settings, apart from ongoing clinical trials.

        1. NICK says:


  23. blogreader01 says:

    Per the “Fraud Guy” …

    “Who would have thought that a serially failed businessman would point people to a product that he invested in that doesn’t work?”


    So, Donald John was always in it for the money? Is that what all your Bernie-Bro friends tell you? Oh but you forgot a key point; to wit, he was going to share his nefarious gain with Putin because Putin has dirt on him. (Which is why he’s constantly cutting Russia slack in each/every way he can.)

    If it’s true, btw, that HCQ es no muy bueno (unless you need it to, e.g., treat your lupus) then here’s hoping The Donald is made aware of this fact. Wouldn’t want that (generally) glorious Trump Train leaving the tracks because HCQ made his ticker go wonky on him.

  24. richard adams says:

    Here is a study that claims HCQ with zinc helps some patients with advanced stages of the disease, in ICU and on ventilators. I haven’t read any study which disputed this.

  25. Julie Aye says:

    Perhaps it’s time to file this topic under the “How Not to Do It” section? Or would this lead to the eventual casting of doubt upon all those good, sound lessons over there? (now if that were to happen, I’d just lose all hope)

  26. Simon Auclair the Great and Terrible says:

    Yes. Enough already, sheesh!
    Lets talk about this:

  27. Petri Volk says:

    I look at the data from the The Brigham Young study in The Lancet (above) and think more data needs to be shown. Specifically, the need for mechanical ventilation was more than double for HCQ/CQ patients compared to control. In clinical practice this should be noticeable not just because of the size of the difference, but also because the effect is counter to the one sought from the treatment (you treat wanting the number to go down) and should have given pause for medics to reduce the use of the treatment.

    A major concern with these retrospective studies is that the treatments are more likely to be given to patients at more severe stages of the disease. Without controlling for severity at admission, the end point may simply reflect that that the treatment is more likely to be given to those with more severe symptoms – inverting apparent causality.

    In the VA and NY studies, there is a clear different on severity at admission for the HCQ groups – for the VA study reflected in the lymphocyte counts. For the NY studies they made a statistical adjustment to try to adjust for differences in severity at admission. Unfortunately, the Brigham Young study is relatively light on detailed admission data – two generalist binary measures – and it is not clear how severity was treated otherwise.

    In the meantime there are a series of positive studies also popping up in the literature but without the same PR fanfare (possibly because their not in the US):
    Madrid –
    UK analysis of Spanish data – DOI: 10.13140/RG.2.2.26151.37281
    South Korea –

    The world is crying out for some decent clinical studies on this. HCQ was identified as a potential treatment at the start of February – the same time as Remdesivir. Meanwhile Remdesivir trials are already publishing data.

  28. JP Leonard says:

    @Kurt, regarding the genesis of what I’m starting to call the “3-pack” treatment for short (HCQ-Zpack-Zn) — a piece in the WaPo dates it to “March 16: Tesla CEO Elon Musk tweets a link to a March 13 paper suggesting that the anti-malarial drug chloroquine might be effective at treating covid-19.” That paper has been removed from google docs for violation of terms of service. On March 16 Musk also tweeted citing an article in Elsevier which has also been taken down, and in he says “Hydroxychloroquine probably better” and links to MedCram Coronavirus Pandemic Update 35 on Youtube. This clip shows a couple of scientific papers on the screen regarding HCQ and zinc:
    Oxford Clinical Infectious Diseases “In Vitro Antiviral Activity and Projection of Optimized Dosing Design of Hydroxychloroquine for the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) .
    And “Zinc ionophore activity of quercetin and epigallocatechin-gallate: from Hepa 1-6 cells to a liposome model” , and “Quercetin as an Antiviral Agent Inhibits Influenza A (IAV) Entry”.
    The episode concludes noting that for the zinc ionophore we have no RCT’s and it’s more important not to be zinc deficient than to try to increase zinc levels by supplementation.
    A large RCT was done in 2008 in a study called “Serum Zinc and Pneumonia in Nursing Home Elderly: “Results: Compared with subjects with low zinc concentrations, subjects with normal final serum zinc concentrations had a lower incidence of pneumonia.”

    Most posters here are trying to use the scientific method. We should not accuse those we disagree with of “religiosity” because they have different views. As human beings we all tend inevitably to use reasoning to support beliefs that appeal to us. That’s a limitation of human nature, but it can lead to constructive discussion.

  29. JP Leonard says:

    @chiz who says “According to the sermo surveys– about 11% of patients hospitalized with covid19 are being treated with Zinc. If it cured them in 4-5 days as Zelenko claimed then I think its safe to say we would have heard about it by now.”
    Couple problems there. Sermo doesn’t break out high dose zinc from minimum daily requirement dose like other supplements.
    50 to 60% of respondents in Sermo surveys worldwide are giving HCQ. This mirrors the overall picture that high dose zinc is the forgotten leg of the triad.
    Also Zelenko’s claimed success is that none of his patients had to be hospitalized, not that he cured them in a few days in hospital.

  30. Joe Psycho says:


  31. Klagenfurt says:

    The truth may hurt, my friends, but I consider you clueless if you are older than your h-index.

  32. Puli says:

    “Early treatment in less severe patients only, in other words.” is not prophylaxis, which is an action taken to prevent disease. Asking a wrong question and addressing it with high-quality data multiple times, and disseminating it in Lancet will serve no purpose. ” Has Hydroxychloroquine been tested as a prophylactic treatment?” Political alignments in the US are blindfolding the Anit-Trump group. Many of the trials so far tested them in subjects already in hospital with reasonable severity of disease or have already acquired it. Just because Trump endorsed I t, it will not deserve a fair look. Seriously, political, social, and economic preference must not blindfold the unbiased scientific approach. Hoping to see HCQ tested in Prophylactic set up.

    1. Athaic says:

      The US is not the only place existing in the world, you know.
      But sure, we meanie Europeans and Asians are all out to get Trump.

      Tell you that: my initial reaction to Trump’s announcement, two months ago, of a “game-changer” was “eh, credit the discoverer, you valor-stealing buffoon, it’s a French doctor who came with the idea”.
      Given the French-bashing propensity of the GOP, that would have been smugly nice to have something to egg them in.
      And then I went to check on this doctor and his studies. Oh boy was I disappointed.

  33. john says:

    I did find it interesting that the government of India is recommending use of HCQ as a post-exposure prophylaxis treatment for healthcare workers. They do cite some ‘anecdotal’ data without providing details.
    Revised advisory on the use of Hydroxychloroquine (HCQ) as prophylaxis for SARS-CoV-2 infection
    The India advisory is dated May 22nd.

    I keep checking David Boulware’s twitter feed for clues as to when his 2 apparently completed trials spearheaded by him at the Univ of Minnesota (early treatment and post-exposure prophylaxis with HCQ) will be published. Would think that it should be very soon now.

  34. hc says:

    randomized hcq studies of any kind may impossible now if participants have entrenched pro or anti hcq feelings and refuse to be randomized to a group contrary to their beliefs . Open lable trials may be the only way to get large number of volunteers.

  35. SALEH says:

    I have just two comments on the Lancet review (sory for my poor english)
    – Patients in this review needed to be hospitalized , they then had to be in serious condition whatever is the origine (infection, arrythmia or else).
    – Then what happened for the hundred of thousand more patients that did’nt even needed to be hospitalized ?? The review dont even mention them.
    -What are the cause of the death in HCQ ou CQ patients arrythmia or infection or Cytokine storm?
    -If the revieuwer statistically excluded the death rate directly in relation with arrythmia, what is the outcome for those who continued the the treatement unharmed compared to control ?. If they had a bad outcome than control groupe, can it be still explained by other confondant factors
    Reading this paper can bring only one conclusion : HCQ Azithro CQ have to be monitored daily and that is all
    Again : – What happened for the hundred of thousand more patients that did’nt even needed to be hospitalized ?? The review dont even mention them.

    1. Some idiot says:

      To summarise your main argument: What about those that were not hospitalised? In there words you are saying that you mean it should be used for prophylaxis. There is no RCT results (yet) to show whether or not prophylaxis with HCQ actually works, although there are a number running/being started.

      1. theasdgamer says:

        “In there words you are saying that you mean it should be used for prophylaxis.”

        Not this. Early treatment in ambulatory clinics.

  36. Kon says:

    Let’s recall a very brief history of CL/HCL as a possible cure for COVID which is important to clearly understand where we find ourselves now in our debates regarding possible effectiveness of CL/HCL

    INITIALLY, there were not one but THREE DIFFERENT stories: (1) a ‘Chinese’ one (wide use of CL/HCL in the initial fight against the epidemic), (2) Dr. Raoult story – a French doctor who prescribed a combination of HCL and azithromycin, and, finally, (3) Dr. Zelenko story – a New York state doctor who claimed success in treating his patients with a mixture of HCL, azithromycin and zinc. All three hypotheses had some real, non-homeopathy type of science behind them.

    However, it was Dr. Zelenko’s letter to Trump that ignited both the President and, as a result of the President relying on his bully pulpit megaphone, wide public interest in CL/HCL. Only after that we witnessed an explosion of political/public pressure that led to the initiation of various CL/HCL studies in the COVID context, including a launch of a number of RCTs.
    We should be very clear what were the initial expectations and what emerged as a criteria for success, albeit not a clearly articulated one, for politicians in many countries (not only Trump) and world public in general – that CL/HCL, maybe not a magic bullet, but at least would provide us with a cure capable of producing SUBSTANTIALLY larger positive effect than the current one identified with the use of remdesivir.

    It is important to emphasize that though in the end it will be, of course, up to the medical/scientific community to decide what works against COVID and what fails, the criteria for the success in the CL/HCL debates has been broadly defined by the uneducated public that does not have a clue about intricacies of biochemistry or statistical analysis. That’s the reality regardless of whether we like it or nor, whether we are ready to accept it or remain contemptuously snarky about it. (Incidentally, the ‘uneducated public’ includes, among others, legions of doctors with University degrees who rushed to order all available supplies of CL/HCL or write prescriptions based on pure hearsay or political leanings).

    That’s how the forces seemed to be deployed on the CL/HCL battlefield 1,5 to 2 months ago.

    So, who is winning?

    If to judge upon the suggested criteria, the ‘Chinese hypothesis’ is headed for a defeat. Though the announced gold-standard RCTs are yet to be completed, various small and large observational studies (especially the last one recently published in the Lancet) indicate that the CL/HCL remedy, though maybe not a complete dud, will fall far short to be truly viewed as a deciding weapon against COVID.

    One might think that the same fate awaits the Dr. Raoult hypothesis (HCL+azithromycin) since those observational studies surveyed the use of azithromycin as well. But, no, I think the evidence here is somewhat less clear because both Drs. Raoult and Zelenko stressed the need to introduce CL/HCL VERY EARLY, within a few days of onset of symptoms. As far as I know, there are no major studies that clear this threshold focusing specifically on whether an early treatment may be a game changer.

    We do not know any details about the RCTs which are underway. But my gut feeling tells me that the early use factor will be also omitted from the established RCT protocols. And it is highly likely that these first RCTs will not consider a possible effect of adding zinc to the cocktail of HCL and azithromycin.

    So my prognosis is that the fierce CL/HCL debates will linger on until either (a) the Drs. Raoult and Zelenko hypotheses are addressed directly and convincingly confirmed/buried, or (b) the scientific community will stumble, in the eyes of the general public, on some other ‘magic potion’.

    So for Dr. Lowe, it is far from the last CL/HCL rodeo.

    1. RA says:

      Perhaps one area of common ground in this polarized debate over HCQ+/- Zn is the need, as you highlighted, to do more research on early-stage treatments. I liked this op-ed on the subject:

      Perhaps we need to be doing more early-stage disease treatment research for a whole host of potential therapies…neither excluding HCQ/Zn nor putting a political thumb on the proverbial scale in favor of it when there are probably other agents or combinations of agents that are worthy of research in early stages of the disease as well. Whether or not HCQ effectively sucks the Zinc into the cell is not the only issue…is it also sucking all the Oxygen out of our way too limited investigation into early-stage treatments overall?!? I’d say let’s test a lot of potential early-stage treatments…wonder if more of those who test positive as outpatients could be quickly enrolled in trials somehow.

      1. john says:

        To RA:
        The zinc ionophore hypothesis is not the only one proposed by which HCQ or CQ may inhibit coronavirus. There is also inhibition of viral entry and acidification of endosomes where the viruses hangout, causing their deactivation.

        1. RA says:

          Thanks! I was mentioning that metaphorically in that sentence, but since you brought it up….If these other mechanisms are key, does that mean we should see some positive benefit in studies of HCQ/CQ without Zinc? Many seem to think (negative) studies are useless without the Zinc. But…if it is the Zinc ionophore mechanism that is determinative, then why is there comparatively little interest in Quercitin or any other Zinc ionophores out there? Is there some head to head data to suggest that HCQ/CQ are more ionophoric than Quercetin? Should we do a HCQ/Zn vs Quercitin/Zn vs placebo early stage treatment trial?!?

    2. John Yoe says:

      I like how this clown condemns HCQ with his great ‘interpretation’ of the Lancet study and then days later goes on to say the study is flawed but only after other researchers question the data integrity. If we cannot trust this clown to critically review content then what is he good for? Anyone can provide a synopsis. Only a real scientist can offer a good review and we do not have that here.

  37. mn says:

    People including this blogger are over interpreting the results. We don’t need your political bias especially when we are talking about science. HCQ alone and other derivatives are statistically not effective for the hospitalized patients in this non-randomized study. That’s it. But that does not conclude that HCQ with either different combination (zinc and etc) or under the various conditions (intervention timing, doses and the consistent categorization of the medical conditions/history of each patients) with large scale randomized control trials are not effective yet.

    For zinc cocktail hypothesis and the earlier treatment (either as prophylactic or very early stage )studies, few with randomized controlled trials are currently undergoing. Until then, there is no need to rush to any conclusions and make fun of other hypothesis’ or being sarcastic because that is very unnecessary and even insulting to a scientific dignity. So stop being black and white and using these studies to justify your political stance/belief.

    Even the authors of the Lancet paper noted ” The association of decreased survival with hydroxychloroquine or chloroquine treatment regimens should be interpreted cautiously. Due to the observational study design, we cannot exclude the possibility of unmeasured confounding factors, although we have reassuringly noted consistency between the primary analysis and the propensity score matched analyses. Nevertheless, a cause-and-effect relationship between drug therapy and survival should not be inferred.” “We also did not establish if the association of increased risk of in-hospital death with use of the drug regimens is linked directly to their cardiovascular risk, nor did we conduct a drug dose-response analysis of the observed risks”

    So yes it is good enough to say that HCQ is(may) not effective under the certain conditions, and yes it is still not enough to conclude that anything related to HCQ (+other combinations with modified intervention protocols) is done yet.

  38. Roger Callaway says:

    I know I’m out of my depth, that’s why I visit. Is the stance of Laboratory Life, Latour and Woolgar well known? They conclude that scientific investigations consist of pushing a hypothesis into the realm of fact by the application of laboratory work. This HCQ conjecture has not moved, and in fact the hypothesis seems not to have been clearly enunciated.

  39. theasdgamer says:

    The Lancet article has problems.

    1. Conflates early data with late data for a novel infectious disease. (Dec. thru April.) That is simply scientific malpractice. Iatrogenic factors dominate the early data. Even March data is suspect. Big oops.

    2. Doesn’t account for zinc levels. Big oops.

    3. The study suggests that giving HC leads to ventilation. That would be news to rheumatologists everywhere.

    Now let’s look at Derek’s article.

    Derek implies that the studies speak against ALL treatment with HC. However, the Lancet study specifically states that it does NOT apply to ambulatory clinic treatment. Because the time from symptom onset to treatment with HC was nine days at best in the Lancet article. Ruh roh, Raggy.

    EARLY treatment. With Zinc. Show me the studies where that HC treatment protocol fails. It’s been advocated for months and used by docs for months so there’s lots of data, but for some reason, no one wants to study it. A retrospective study could put it to rest. Why hasn’t it been tested?

    1. Daniel Vieira says:

      There are another major problem, when excluding from the study patients that received chloroquine or it’s variants later on the course of the disease, they are selecting only success cases of many centers that included “chloroquine” on the protocols for severely ill patients. Just to illustrate, the mortality rate in the control group (9%) is way lower than the mortality rate for hospitalized patients in NY (about 30%) or in Spain (about 23%).

      1. theasdgamer says:

        The Lancet article says that patients were tested, then treated with HC. In the hospital. Probably seven days after system onset. Add two days to get lab test results (best case and only for later cases…it took longer with earlier cases…maybe 7 days) + up to 48 hours for treatment…so the treatment after symptom onset could vary from 10-11 days for later cases to 15-16 days for earlier cases.

        Another point. Look at how the study authors determined disease severity. They used qSOFA (which we now know is a poor indicator of covid mortality) and pO2 <94% (which is also a poor indicator because it's way too high). The data was cherry picked to overwhelm the HC data with barotrauma data. Patients were included who were ventilated prematurely. Early cases. Loaded with LOTS of early cases.

        Lymphopenia would have been a much better indicator of disease severity.

        1. KazooChemist says:

          Right, wrong, flawed, or rigorous it doesn’t seem to matter. The WHO has paused testing hydroxychloroquine in its Solidarity trial apparently on the basis of the Lancet article.

          1. theasdgamer says:

            The game is rigged.

          2. theasdgamer says:

            Recovery is proceeding despite WHO’s efforts. All of Asia except the Philippines is rejecting WHO’s suggestion. Even China. Imagine that!

            WHO’s game seems to be politics, not science.

    2. RA says:

      I agree we need better early-stage/outpatient treatment studies…but of a lot of different cocktails/approaches…perhaps retrospective to start, but clinical trials ultimately…let’s let good data be our guide.

      But, I have to ask…why is it almost June and we don’t yet have early treatment HCQ/Zn data when the President is an active proponent of this protocol and there is apparently no shortage of people using it? He[‘s not shy about exercising his power….I would think he could have made a few large scale, decent quality studies happen by now…WITH ZINC! Done in the Zelenko way! I would think if he wanted a fair assessment of the hypothesis, he could have made it happen by now!!! Why hasn’t he?

      1. drsnowboard says:

        I would argue that Trump, along with a large coterie of commentators on this blog , are only interested in positive results for their declared regimen. Sadly, science and clinical practice only advances by publishing AND TAKING NOTICE of negative results. If we are pushing regimens into ambulatory clinics (which in Europe folk are discouraged from attending as an infection risk) then the trials will have to have massive patient numbers to be sufficiently powered to show a +ve result. If we take 80% are going to resolve ‘naturally’ then we are showing a difference on the 20% progressing to hospitalisation. The variability of who will be hospitalised will also mean larger numbers. If this wasn’t a pandemic , pretty sure Pharma would be identifying the smallest patient cohort who are most at risk and giving them a drug pack as soon as they showed symptoms. Perhaps BAME diabetics without coronary complications over the age of 60…

        1. theasdgamer says:

          Actually, clinical practice advances independent of science oftentimes. When scientific experts were giving bad advice early during this novel infectious disease epidemic, docs were having to observe their patients carefully and use their expert judgment about treating their patients. Science is of more value once a disease is well understood. The understanding occurs first among clinicians. At this point in the covid epidemic, I rate clinical expertise over scientific expertise.

        2. RA says:

          Thanks! Agree that a potential early stage treatment has a higher bar to clear because most patients will recover with no intervention, so any potential harm to all of those folks needs to be balanced against the benefit for those who are would progress to severe disease. Which is why we need to do the research and I am puzzled that those who say that treatments will work at early stages are doing very little to actually promote early stage research…maybe it could be done via telehealth instead of clinic visits or in nursing homes where the logistics would be easier.

        3. theasdgamer says:

          Maybe 80% will become infected without needing treatment, but giving an early regimen may reduce the need for hospitalization where the patient might otherwise not have survived. Early treatment is still potentially an advantage. So, no, we aren’t necessarily looking at the cohort progressing to hospitalization.

        4. theasdgamer says:

          I have been actively searching for family physicians (GPs) who have tried Zelenko’s protocol but have quit using it because it didn’t work. I have yet to find a single one. But I am trying hard to disprove his protocol. I find docs who confirm Zelenko’s protocol, but none who disconfirm it. On occasion I find family physicians who quit using Zelenko’s protocol because a hospital pressured them, but none who did so voluntarily. So I’m not just looking for confirmation. If anyone can find family physicians who have tried Zelenko’s protocol and discontinued using it, please respond to this comment.

          1. Some idiot says:

            This is a very good point, but I suspect you will probably have great difficulty finding any, simply because most recover (thankfully!), so therefore whether or not it works, it will be almost impossible to show it in this manner.

            I know from our comments that we have different views on this topic, but I really appreciate the way you are approaching this from a data-based approach (you are one of those trying to generate more light than heat! (-: ). But I really have difficulty seeing how a clear answer will come prior to RCTs using this protocol…

          2. theasdgamer says:

            Dear Mr. idiot,

            Even if 80% of covid patientsrecover, we can do statistical checks of data samples’ fatality rates based on average fatality rates for covid if the samples are large enough.

            For example, if you do checks on Dr. Zelenko’s claims of 1450 patients treated with 6 hospitalizations and 2 deaths, the odds that his treatment isn’t better than a placebo are miniscule.

            You can also check hospitalization rates of fam med docs’ patients with tx v. no tx.

            Sometimes science can’t help. You have to rely on art (anecdotal evidence from clinical experts).

            We rely on anecdotal evidence all the time. Sun rising in the east. Water being wet. Only sure things are death and taxes.

            The data is strong enough for tx that there should be no prohibition of using the tx.

          3. Some idiot says:

            Again, I disagree… Not meaning to criticise any given researcher, but it has been shown time and time again that without randomised, double-blinded trials, biases will always creep in. And given that (thankfully!) most people recover, that makes the stats tough…

            I would like to believe that it worked in the way that you believe it works, but we have nothing but anecdotal evidence. But anecodotal evidence is a good starting point for proper trials. Nothing more.

            You say that we use anecdotal evidence all the time, and you talk about the sunrise and water being wet. We _know_ that the sun rises in the east, because we have _defined_ that to be the case, and have later backed it up with observational and mechanistic studies. This is not anecdotal, this is properly studied. We describe water as being “wet” because it wets many surfaces (this has been fully and properly studied). There are also surfaces that water does not wet effectively. There are many other solvents that either wet or otherwise surfaces. There are handbooks full of precise data on such matters.

            When engineers/architects build bridges, do they say “let’s use this metal beam… it worked last time; this bridge is a bit longer, but it is probably fine”? No, of course not. They go to a database of data for the different materials to find out precisely how strong it needs to be, and from building regulations what appropriate safety factors should be. Not anecdotal evidence. If is seen that a particular part seems to be either stronger or weaker than expected, then this is anecdotal evidence which suggests that it should be examined methodically in detail…

            Medicine should be the same… Anecdotes can be really excellent starting points, especially coming from experienced clinicians, but must be properly tested before accepted. History has shown this again and again.

      2. john says:

        To RA:
        I’ve been following Dr. David Boulware’s twitter feed, because he has completed both the his early treatment RCT as well as his post-exposure prophylaxis RCT using HCQ. AFAIK, zinc was not given as part of the protocol. Because the protocol demands a positive PCR prior to entry, probably the earliest patients were getting on the ‘early’ treatment protocol were 4 days after onset of symptoms. However, the post-exposure prophylaxis RCT, assuming that they have a sufficiently high event rate, should address the earliness of treatment issue.

        In any case, in a tweet today, Dr. Boulware writes:

        David Boulware, MD MPH
        What did I do on my holiday Sunday? Did some great hiking on the #SuperiorHikingTrail overlooking Lake Superior… and spent 7 hours on manuscript revisions. All minor, but redrawing a supplemental Figure and reworking Appendix materials took some time to get right and get pretty”

        The good news is, that the data are being written up. They should be available soon, as the needed manuscript revisions are described as ‘minor’ (although one never knows). The bad news is, that the time to posting on an on-line journal website is probably at least several weeks away.

        1. theasdgamer says:

          If zinc IS important to symptom relief (and maybe viral clearance), then a RCT should at minimum test zinc levels.

        2. RA says:

          Yes, that is good that more data is coming…I think he said in a twitter comment that 20% of the patients were on Zinc and it will be addressed. I am puzzled why there is no sense of urgency in releasing the results..especially if the requested revisions are minor and his current focus is on hiking and getting the paper “pretty!”

    3. humblemathematician says:

      I totally agree with your comments. This seems to me more classical research bias than shenanigans. All the anecdotal evidence for HxyC are either of very early stage cases or when used as prophylaxis. Yet, all the studies involve hospitalized patients. Mind boggling.
      Later on you commented that all of Asia except the Phillipines are using HxyC. I know India is using it, because it is now officially part of their national recommendation in certain cases (the right cases, from what i can see). Do you have references regarding other countries in Asia?

      1. Robert Clark says:

        Humblemathematician, I posted some links in a comment today, May 31st, about Asian countries successfully using HCQ to treat COVID-19.

        Two key facts: 1.)COVID-19 death rates are markedly lower in countries where antimalarial medications are in widespread use, either for malaria treatment or COVID-19 treatment.

        2.)Asian countries, where there has not been this promulgation of anti-HCQ bias, have been much more open to prescribing HCQ even in early use, unlike Western countries who only give it late in severe disease condition, have markedly reduced death and hospitalization rates.

        Robert Clark

  40. john says:

    Latest video by Pr. Raoult:
    with comments on the Lancet study.

    He discusses the point that they now have done more than 10,000 EKGs in outpatients following the HCQ/Azithromycin regimen, and while he is not specific, the implication is, that there has been no problem.
    See time marker at 4:50 (turn on CC, closed captioning)

    He also does discuss zinc; apparently they found that plasma zinc levels correlate with disease severity.
    See time marker at 3:00

    He then makes a point about arrhythmic deaths. They have now “treated” (though it is not clear if all were treated with the HCQ/AZITHRO regimen, more than 3600 patients.

    I personally believe that both the Lancet study could be true, as well as Raoult’s result with early treatment with HCQ being safe and probably efficacious.

    In any event, one happy note is, that it appears that in Marseille, at least, the epidemic is largely over, with very few new cases popping up.

    1. David Young MD says:

      Somehow, I just don’t trust him. First of all, Raoult himself did not treat 3,600 patients. So… just who is it that treated 3,600 patients? Are there another dozen physicians who are part of this “study?” And what happened to all of them? And most importantly, did they treat 3,600 patients who were not really that sick from Covid19? Is he cherry picking those who are not critically ill and thereby getting “good results” because they would have fared just as well without the Hydroxychloroquine and Azithromycin. His 3,600 patients have not been submitted to a protocol, as far as I know. Did they sign consents? Is a publication in progress? Has it been peer reviewed? There is a lot missing here.

      1. john says:

        The IHU appears to be a pretty big place – sort of a combination outpatient and inpatient hospital as well as a research center.

        They don’t list their staff, but on one of the videos, Dr. Raoult is shown with about 10-12 medical colleagues, many of whom appear to be research associates. The IHU budget is several million euros per year.

        Here is their report on treating approximately 1061 patients (abstract released on April 9th). They did not treat all comers.

        You can see the flow chart of the excluded patients here:

        Raoult has been against doing an RCT on his patients — his point is, that the treatment is quite safe, there is in vitro evidence of its anti-viral activity in vitro, and so an RCT would not be something that he would feel comfortable doing. The IHU is primarily a treatment and educational center. They are extensively involved in research, but not, AFAIK, in doing randomized trials.

        The argument remains, that perhaps the patients would have done as well or better, without the prescribed treatment.

  41. Al says:

    I analyzed the study and compared it to a couple of other similar published studies, which show that there was no effect of HCQ on the patients, no positive nor negative. Where the Mehra study is showing more than doubling of mortality in HCQ group. The Mehra study appears to have flaw in the way propensity score matching with too little variables. I discuss it in the link, bellow, what do you guys think?

  42. john says:

    Becoming more skeptical about the Lancet report re arrhythmia incidence:
    On more careful reading, I am getting a bit less impressed with the arrhythmia part of the Lancet observational dataset.

    1) They define arrhythmia as EITHER nonsustained or sustained ventricular tachycardia.

    Sounds bad, yes? But, they never separate out their results into nonsustained vs. sustained tachycardia.

    What, exactly, is the definition for nonsustained ventricular tachycardia?

    “Nonsustained ventricular tachycardia (NSVT), defined as three or more consecutive ventricular beats at a rate of greater than 100 beats/min with a duration of less than 30 seconds (waveform 1), is a relatively common clinical problem” [1]
    1. ACC/AHA Task Force. Circulation 2006; 114:2534.

    Now if you look at the incidence rate in the Lancet paper:
    Compared with the control group (0·3%), hydroxychloroquine (6·1%; 2·369, 1·935–2·900), hydroxychloroquine with a macrolide (8·1%; 5·106, 4·106–5·983),
    chloroquine (4·3%; 3·561, 2·760–4·596), and chloroquine with a macrolide (6·5%; 4·011, 3·344–4·812) were independently associated with an increased risk of de-novo ventricular arrhythmia during hospitalisation.

    In these very sick patients, I find that an incidence of nonsustained V-tach in the control group of only 0.3% is EXTRAORDINARILY low.

    The most likely explanation is the old adage in medicine: “You find what you look for”.

    In the Lancet paper, it is not at all clear how the prevalence of NSVT (non-sustained V-tach) was determined.

    “The secondary outcome of interest was the association
    between these treatment regimens and the occurrence of
    clinically significant ventricular arrhythmias (defined as
    the first occurrence of a non-sustained [at least 6 sec] or
    sustained ventricular tachycardia or ventricular fibrillation)
    during hospitalisation.”

    But it is not at all clear how this arrhythmia data was collected or looked for. Believe me, in ICU patients, or patients on ventilators, all sorts of transient ventricular arrhythmias happen, and not merely 0.3% over the entire course of their hospitalization or over a several day follow-up.

    It is entirely possible that the treating physicians were monitoring or tracking ECGs to a much greater extent in the patients being given HCQ or CQ and/or a macrolide.

    Also, I suspect that the incidence of sustained V-tach in all groups was much lower, and not statistically different. This is an important piece of missing data.

  43. john says:

    Sorry for being persistent: In observational studies there are two types of important bias. SELECTION BIAS, which we all know about. And in the Lancet study, the big unresolved question is: Did the docs treat the more severe cases with the novel meds? However, also important is ASCERTAINMENT BIAS. Namely, it is likely that the outcome variable that you’re interested in was measure more frequently, or differently, in the group at interest vs. controls?

    Now, the authors give absolutely no info in terms of how NSVT (non-sustained V tach) in their study was measured. In hospitalized patients, esp. those in ICU, one normally does not routinely order paper ECGs, as the patients are on monitors. However, if one is worried about prolongation of the QT interval, for example, in a given patient, one will order a paper ECG, and given thatn NSVT is fairly common, this would lead to a certain incidence of NSVT that would not show up in controls, if the amount of paper ECGs ordered in the control group is less. To me, this would explain the low incidence (0.3%) of NSVT in the controls (I think it’s a serious underestimate).

    The prevalence of NSVT depends entirely on how the ECG trace is analyzed, and will, of course, be much higher with 24-hour ECG monitoring as opposed to a standard rhythm strip. Unfortunately, the Lancet study presents absolutely no information as to how this key secondary outcome was measured.

  44. PP says:

    There are a number of awry aspects in the Lancet paper.

    1) An observational study on nearly 100,000 cases in 671 hospitals,
    signed not by a multicentric team by just 4 authors.

    2) No acknowledgemnt of any sort at the end of the paper (funding, sources, insititutions,

    3) Data acquisition came through a “cloud-based health-care
    data analytics platform” provided by Surgisphere a company who’s CEO
    is the second author of the paper.

    4) No data on dosage of regimens were reported, while (high) dosage is critical
    for the HCQ antiviral obsrved effect in vitro.

    5) “within 48 hours of diagnosis” does not necessarily imply that the
    initial conditions were uniformely less severe

    6) The mortality rate of the 96000 (17%!) is far too high for the whole
    sample (median age 54.3) and especially of non survivors whose
    *median* age was only 60. From official data sources, the mortality ratio
    at 60 is in the range 2 and 3.5% in China, Italy, Spain and Soth Corea.

    1. Christopher says:

      There are more rumblings about the paper on Andrew Gelman’s blog:

      This is the same blog that disputed the Stanford studies of Santa Clara seroprevalence (in that case arguing that their computed infection fatality rate was inappropriately low).

    2. David says:

      PP: 1) The paper is by the team that pulled the data and analyzed it. It’s common practice for papers from registries and databases to not list the people who enter the data (use the registry). 2) Acknowledgement is clearly stated (look for “This study was supported by …”) at the end of the paper, ahead of the references section, where it belongs. Also stated was conflict of interest information. 3) The information came from a database tool developed by one of the authors. Tool development effort is why that person was one of the authors. Seems pretty obvious, no? 4) Dose regimens of HCQ and CQ were clearly stated in text (“The mean daily dose and duration of the various drug regimens were as follows…”) 5) Initial conditions were assessed for severity, which was incorporated as a covariate in the analysis. 6) The mortality rate is not “far too high” considering the study population was drawn from people who were all hospitalized.

  45. SALEH says:

    I dont have any opinion about those thousand of patients who took HCQ at home and tolerated the treatement , upon the shared opinion of many profesionnals working in “real life” HCQ beleive it works .
    All what I say is that Lancet in this review is biased because the cohort in the treated groupe had been admited to hospital for a reason that we ignore (they are not starting from zero)If those reasons have to do with their treatement, then they start with a “statistical” handicap (they are not a sufficiently neutral cohort in the starting block évoluting to one direction or onother).
    Maybe many patients of the treated patient did not tolerate their treatement and that is the reason for hospitalisation and thats why ( maybe also ) that they are over represented in the treated groupe.
    It would have been better to observe what happens in outpatients , in the général population (not in hospitals).
    This Lancet review does not reflect “real life” as pretended by the author.
    As for the quality of trials and reviews it all depend their design. Even the best RCT have their own weaknesses
    In this case, Its like looking at the whole picture trough a microscope

  46. donorcure says:

    The potential misuse of hydroxychloroquine during the COVID-19 pandemic poses serious risks to patients with lupus who are socioeconomically vulnerable. Pharmacy shortages could lead to a black market for the drug, rendering it unaffordable for many patients with lupus.

  47. ULRICH LINGNER says:

    Today published result of a research in Brazil. Breves, in the state of Para, population 100.000, already infected 24%. For now, 53 died from covid-19, about 0,22%. The region, on the Marajo Island, has highest incidence of malaria in Brazil and people probably make prophylactic use of chloroquine. This would eventually favor the prophylactic use of this drugs, maybe only people without cardiovascular issues.

    1. JoeB says:

      The Brazil study OVERDOSED it’s patients.
      The dosage of HydroxyChloroquine is the key to side effects, it’s only at an extremely high dosage that side effects become evident, not at the dosages used for Lupus, Rheumatoid Arthritis, and will be given to the CHINESE VIRUS patients.
      Lupus and Rheumatoid Arthritis patients have to take the HydroxyChloroquine for years, for the CHINESE VIRUS, dosing will be at the same daily level, but for 6-10 days only !

  48. Nick says:

    Some light youtube entertainment.
    May offend

  49. Anon says:

    Ok, so here you are taking a drug that has been studied as an antiviral for decades and throwing it out it out the door before proper double blinded studies have been done. Most of the new studies were retrospective. Just google it, and moreover there are a ton of doctors that question these studies. Again, just google it. I dont know how many ” cures ” pharma has concocted and they later turned out to be wasted money. The only difference this time…..” orange man bad”!!.

  50. SALEH says:

    Anyway the Lancet review does not represent the whole picture (patients that did not experience side effects). It represent only those patiients sick enough to needed be admitted to hospital.
    Most other alternatives have their oun side effects not to mention their hyge price
    The only lesson from this publication here is that HCL Azithro has to be correctly monitored (specially in severe cases since COVID19 can cause cardiac damage)

  51. Edward R says:

    India seems to be seeing positive results when HCQ is used as a prophelactic by healthcare workers

    1. RA says:

      India also seems to be doing quite a bit of business exporting hydroxychloroquine to other countries, reversing earlier decisions to keep it all for 1.2 billion of themselves!!!

      Modi, Trump, Bolsanaro…all pushing hydroxychloroquine, all far right wingers who like to oppress minorities, all in countries with bad outbreaks, and apparently all collaborating on hydroxychloroquine!

      Coincidence or connection?!?!?

  52. Edward R says:


    Yes that’s not entirely beyond the realm of possibility RA. Money owns politicians after all and with all that excess HCQ capacity India has thanks to Fauci and the WHO impacting their sales you never know.

    If on the other hand HCQ is proven effective then the CDC, FDA and WHO are toast and the lawyers will descend like a plague of locusts on the rest of the medical establishment.

    Time to put on my N-95 and head to the store for some popcorn. This will be epic!

  53. Erik Dienemann says:

    The Lancet study does leave some questions, but, IMO, they’re only about whether the conclusion of greater mortality with HCQ/CQ (with or w/o macrolide) treatment is statistically valid or not. It would require a huge, huge change in the outcomes from this study to find any HCQ/CQ efficacy in hospitalized patients, which is consistent with the NEJoM, JAMA and many other studies. And that, to me is the bigger point and I think we can take that one step further.

    A good estimate of the percentage of NYC hospitalized patients on HCQ for the worst part of the outbreak is probably somewhere between 60-80%. The JAMA study in NYC had 82% of 1438 randomly selected patients treated with HCQ or HCQ/AZ (not including the AZ only patients), whereas the New England Journal of Medicine study had 59% of 1376 consecutive patients (1446, actually, but some were excluded) treated with HCQ. The JAMA study enrolled from 4/9-4/27, which was probably at the height of the HCQ treatment frenzy, while the NEJoM study enrolled from 3/7-4/8, which probably explains why it had a lesser % of patients on HCQ (the media frenzy on HCQ started around 3/20).

    If we assume the NYC HCQ/CQ treatment prevalence data of 60-80% is correct for NY and the US (and probably many other countries) then without even doing any “studies” it’s not hard to conclude that HCQ/CQ offer no mortality reduction benefit, given that US case fatality rates steadily climbed from 2.9% as of 4/1 (when all deaths would likely have been from cases before HCQ use skyrocketed, given the 2-3 week delay from infection to death) to 5.8% as of 5/1, while the NY rate went from 3.9% CFR to 7.8% (no surprise, given NY had 30-40% of the US deaths). Surely, if 50, 60 or even 80% of patients were being treated with HCQ, if it offered a mortality benefit, would we have seen the CFR double? I would think not, but then again, to kind of paraphrase Doctor McCoy, I’m an engineer not a doctor, dammit.

    The data on treatment of mildly symptomatic patients with HCQ is going to be even more variable, IMO, since the vast majority of mildly symptomatic patients get better without treatment, so these will need to be large trials to provide the statistical power to discern any benefit (unless it’s large). And prophylaxis? With 80% of he population only getting mild symptoms or no symptoms at all, good luck with that. But at least some of the trials coming out are controlled/random/blinded.

  54. Rob says:

    We are never going to settle this without randomized, controlled trials. Think of the years and years it took to settle the tobacco debate, where RCTs aren’t possible. And there you had a very large effect, dose/response, an easily understood mechanism and consistent observational studies all over the world. I hope the trials report soon; let’s hope they are unambiguous.

  55. Firte says:

    I am genuinely confused. Allegedly the death rate in Marseille is one fifth of Paris and even lower in prof Raoults hospital yet. Anti hcq people do not address this and prof R and his supporters don’t write a paper showing this.

  56. Robert Clark says:

    It really wasn’t early treatment despite what was said in the paper for reasons explained here:

    Also, the cases in the Lancet article were those diagnosed from Dec. 2019 to mid-April. During this earlier time, it took several days to get test results back sometimes as much as a week:

    So for most cases in the Lancet study the actual time between symptom onset to treatment was likely greater than two weeks.

    Robert Clark

  57. Robert Clark says:

    A major problem with the study was identified here:

    Hydroxychloroquine: When medical science starts to look like political science
    May 23, 2020

    There were more than twice as many patients on ventilators among the HCQ group compared to the non-HCQ group. The key question then is this: was the HCQ the cause of the increased ventilator usage or were the authors adjustments to the data insufficient to compensate for the fact the HCQ patients were sicker to begin with.

    I’m inclined to believe the latter because while HCQ is known for causing heart problems it is not known for causing breathing problems.

    Robert Clark

    1. Miguel MZ says:

      So happy to read you and your fine analysis. Feel less lonely.

  58. Miguel MZ says:

    This is an infox also called fake news. Biased over-interpretation. What the article should conclude from the data analyzed is that HCQ (with our without other) treatment is not useful for severe/advanced Covid cases and that HCQ should not be prescribed to people with certain cardiac symptoms. All this has been known for a long time, nothing new on the horizon. In “outcomes” of the article, look at the number of patients who have reached the “Mechanical ventilation” stage. The groups with HCQ have higher percentages, except that this treatment has no side effects that could lead to a need for “mechanical ventilation” the covid yes. It can be deduced from this that the patients in the HCQ groups were patients in a much more serious condition than the control group. Conclusion biased analysis. Here is the opinion of some experts in the field on this study (sorry in french but could be translated easely):

    Here is the translation of the link :
    Study on 96032 medical files from 671 hospitals on 6 continents.
    Patients hospitalised between 20/12/19 and 14/04/20 – Publication on 21/05/20 – 4 authors signatories Hats off! A record of efficiency for data collection, translation of the different foreign languages including Asian + statistical analysis + writing article + reviewing + publication!
    At the very least, a publication at 50 million euros. Who financed it?
    And we pass over the links of interest declared by the authors with the pharmaceutical industry (see page 9).

    -FLOW INCLUSION CRITERIA e.g. coprescriptions of antivirals in 40% of cases, with no information on their distribution in the groups analysed.
    -IMPRECISIONS ON ANALYSIS TREATMENTS: These are called macrolides. Impossible to know WHO RECEIVED AZITHROMYCIN
    -PATIENTS WITH COMORBIDITIES that do not make a representative population (e.g. 1 in 3 patients with hypertension in the hydroxychloroquine + macrolide group).
    -NON COMPARABLE GROUPS: ex HCQ* group + more severe macrolide with 20% mechanical ventilation versus 7.7% of patients in the “control” group, idem on SaO2 parameter ˂ 94
    While it says “No significant between-group differences were found among baseline characteristics or comorbidities. “Foot note” in Table 2 is surprising: “Age and BMI are continuous variables.
    “The 95% CIs have not been adjusted for multiple testing and should not be used to infer definitive effects.”
    -NO INFORMATION ON MISSING VALUES ” ” multiple imputation for missing values was not possible ” ” it was assumed that the characteristic was not present ” – it is obvious that missing values have to be relied on a multi-country multi-centre analysis with varying care
    and the list goes on and on… But was the Reading Committee taking a nap ????

    Enough of such misinformation! Who’d better make believe that Hydroxychloroquine is ineffective
    and dangerous when properly prescribed?

  59. SALEH says:

    One main dilemma is what motivated of being hospitalised. How bad where they clinically upon admission, What was the delay time between onset of symptoms and starting of the protocols
    All in all those patients cant represent the real world treated majority that did not need hospitalization.
    As for RCT I have read hundreds of them and in most of them the conclusions are rarely franc (like: “yes we can see some improvement but the results have to be verified” ) One known problem with RCT is a usually poor external validity (the patients selected do not resemble to those in real life). Its much demanding in term of resources etc and hard to conduct in full pandemic
    Hope that I am wrong this time but I am sceptical concerning RCT
    A good observational study might be less precise but can make more sense especially an emergency RCT in a stressful atmosphere of a pandemic.
    Raoult believe that HCQ-Azithro works , he says that there is a presumption of efficacy in vitro and in his own research Center in Marseille and to a very large extent. He is also saying that the patients tolerated his combination (hundreds of ECG)
    He thinks that it is unethical just to send back people home telling them to wait until the first signs of suffocation and that it is a duty for a doctor in such an emergency to use available medication event without full trials to try to help them and I believe that this position is difficult to criticize.

  60. john says:

    Interesting 46 min. interview with Pr. Raoult by André Bercoff from May 27th, where Raoult comments on some potential shortcomings of this Lancet paper, plus comments about other issues in peer reviewed articles in the field.

    Unfortunately, closed captioning is not available, so you need to understand French.

    It appears that the French government has used the results of the Lancet study to ban use of HCQ, even in an outpatient setting (not sure about this). This shows how politicized this issue has become. I don’t think that government bureaucrats are equipped to critically judge scientific articles, and such jumping the gun is not a good thing, IMO.

    1. Robert says:

      John — you write that “This shows how politicized this issue has become.” It shows no such thing. The issue has been “politicized” in the U.S. mainly by a subset of American politicians and their followers, and not by health care professionals. Further, the “government bureaucrats” you refer to are the French health ministry. They have a responsibility to evaluate incoming health data and make recommendations for France. That would be their job. They appear to be doing it based on the data they have available to them at this time. For them to simply ignore the Lancet article might be considered irresponsible. As to whether it has been “politicized” in France, I will leave that up to any French correspondents who frequent this site. I am not French, so can’t comment on that.

    2. WST says:

      Prof Raoult’s latest paper,
      By testing 101,522 samples by polymerase chain reaction (PCR) from 65,993 individuals, we diagnosed 6,836 patients (10.4%), including 3,737 included in our cohort. The mean age was 45 (sd 17) years, 45% were male, and the fatality rate was 0.9%. We performed 2,065 low-dose computed tomography (CT) scans highlighting lung lesions in 581 of the 933 (62%) patients with minimal clinical symptoms (NEWS score = 0). A discrepancy between spontaneous dyspnoea, hypoxemia and lung lesions was observed. Clinical factors (age, comorbidities, NEWS-2 score), biological factors (lymphopenia; eosinopenia; decrease in blood zinc; and increase in D-dimers, lactate dehydrogenase (LDH), creatinine phosphokinase (CPK), and c-reactive protein (CRP)) and moderate and severe lesions detected in low-dose CT scans were associated with poor clinical outcome. Treatment with HCQ-AZ was associated with a decreased risk of transfer to the ICU or death (HR 0.19 0.12-0.29), decreased risk of hospitalization ≥10 days (odds ratios 95% CI 0.37 0.26-0.51) and shorter duration of viral shedding (time to negative PCR: HR 1.27 1.16-1.39). QTc prolongation (>60 ms) was observed in 25 patients (0.67%) leading to the cessation of treatment in 3 cases. No cases of torsade de pointe or sudden death were observed.

      Early diagnosis, early isolation and early treatment with at least 3 days of HCQ-AZ result in a significantly better clinical outcome and contagiosity in patients with COVID-19 than other treatments. Long-term follow-up to screen for fibrosis will be the next challenge in the management of COVID-19.

    3. Robert Clark says:

      About the Raoult video John, youtube offers automatic captioning. Perhaps that option wasn’t visible because you were looking at the mobile version.

      Open up a browser window on your computer, tablet, or cell phone and paste in the address bar:

      On a mobile device you may have to tell it to do a desktop version to see all the options.

      There should be an icon “cc” visible beneath the video window. You can turn captioning on and off there. To the right of that icon there is the usual gear sprocket icon indicating settings. Select that and you can also choose an auto translated language such as English.

      Unfortunately when I tried the auto translate to English it was pretty poor. I don’t speak French so I can’t tell if the autocaptioning in French is any better.

      You can also do a transcript of the video. At the end of that line beneath the video window that has the thumbs up and thumbs down voting icons, there is the usual horizontal three dots icon that brings up a menu. You can select there to show a transcript of the captioning. If you selected auto translate to English that will be the language the transcript is in. As I said though the translation is pretty poor.

      You can drag over the transcript to copy and paste the transcript text to save it. It might be if you copy the French transcript and copy that into a google or other computer translator you can get a better translation to English.

      Robert Clark

  61. NICK says:

    Here is the question for the people who hate the use of hydroxychloroquine and Zinc with or without Azithromycin.

    You elderly mother or father gets infected with Sars COV2.
    We have zero treatments as of today.
    First day of symptoms of – fever – lose of taste and smell and cough.
    They wait and get tested as the symptoms worsen and the results come back positive – now they are having difficulty breathing and body aches.
    All of you that are researching the hell out this, what advise do you have for your parent who is now struggling to move and breath.
    Do you let the hospital treat them? The hospital said we will not give HCQ and Zinc as treatment because there is no evidence , what we can do is give provide supportive measures and ventilators if needed.
    So far from all we know , I can only come to one conclusion . Go to a doctor brave enough to prescribe HCQ and give it with Zinc. This is all you need you are not treating the world , its one pt at a time – if there is no options why the such a heavy push back against something that could work in theory or anecdotally.
    If you do not decide to use HQC and Zinc with or with out Azithromycin, what are all you people against this treatment going to do what options can you offer with all this researching you do?
    I would = Treat it as early as possible with HQC and zinc and K+( to reduce QT prolongation).
    Make a Iodine nasal spray. Povidone Iodine 1ml in 30 ml of Saline Nasal spray.
    Take Vit C 1000mg 4 to 6 times a day
    Take Vit D3 6000iu per day with Vit K2 100mg ( M7&M4)
    Take SOD ( Super oxide dismutase)
    Take Glutathione
    Take a multivitamin- to get other minerals and vits
    You anti-HQC crowd make this too complicated – there is no treatment so use it if need – if a better treatment come along use the better newer treatment but until then will you let your parents take the chance of dying without any treatment.

    1. NICK says:


    2. drsnowboard says:

      You know there is no evidence for those vitamin overloads, right? None. Maybe look up one word. Homeostasis. But you do you. And if they still die, when you might have got them remdesivir?

      1. NICK says:


      2. NICK says:

        Let give you a 1/2 tsp
        Plasma vitamin C concentrations and risk of incident respiratory diseases and mortality in the European Prospective Investigation into Cancer-Norfolk population-based cohort study

        1. Some idiot says:

          Just curious: did you read the conclusion? The used vitamin C not as an absolute number, but as a marker for fruit and vegetable consumption. In other words, people who ate healthier (by this measure) had a better HR…

          1. NICK says:

            It was a 1/2 tsp worth.

            High-Dose IV Vitamin C on ARDS by COVID-19: A Possible Low-Cost Ally With a Wide Margin of Safety

      3. NICK says:

        @drsnowboard. person deficient and a person with optimal nutrition ( with supplementation) will both be in homeostasis. The idea of homeostasis is a very narrow insight , we are born we are homeostasis and at old age we are in homeostasis but bigger picture lot has changes. When we age our levels of lots of chemicals we need are produced at a lower level even if the intake is sustained yet we are in homeostasis. There positive and negative feed back loops, protein binding and redundancies of other systems that keep the homeostasis. Usually in nature , the design is multi functional.
        Simple experiment – if you or anyone you know who have bleeding of the gums while brushing – take 1000 mg Vit C orally once daily – and you will notice the bleeding will stop in most cases. And all this while the body is in homeostasis.

    3. Nate says:

      Sorry, but you are in a science blog. This is not how it works. You don’t say, well we can’t “do nothing” so we’ll just throw the kitchen sink at it. That’s highly irresponsible medicine and basically amounts to live experimentation on sick patients with no regard to safety or efficacy. Just because we are in a pandemic we do not throw the basic tenets of science and medicine out the window to make ourselves feel like we are doing something. Best case scenario your treatment doesn’t help. Worst case scenario, you do actual harm to patients – see HQC treatment and increased mortality.

      1. NICK says:

        Question was how you would help your elderly parents. Sometime you don’t have the luxury of time and data and must make a decision. You didn’t answer the question what you would do, I answered what I would do for my parents.
        Again what would you do?

    4. Robert says:

      Nick — I don’t have a good answer for you. Neither does anyone else at this point. However, I will agree with your third statement: “We have zero treatments as of today.” This is true regarding proven pharmacological treatments or vaccines as of today, but hopefully not forever.

      However, there are suggestions in the literature for other approaches (other straws to grasp, if you will, or other approaches to study). One of these is now about 15 years old, and is a suggestion to study the use of statins in pandemic influenza. The suggestion comes from David S. Fedson, a professor (now retired) at the University of Virginia medical school. The original proposal came to the group I was part of around 2005 or so (I was a medicinal chemist at Novartis working on a statin project at the time — now retired). The basic idea was NOT that statins have any direct antiviral activity, but rather that, due to other effects of that class of drug, they may mitigate the host response to the virus, thereby possibly reducing mortality. These are the so-called pleiotropic effects of statins, and are largely anti-inflammatory in nature. The author (Fedson) was hoping to persuade statin makers to study this. We declined at the time. I thought the proposal was interesting, but our infectious diseases group declined.

      Here is a link to the original proposal:

      There is a substantial literature related to this now. If you want to look further, here are some searches you could try:
      • Statins and endothelial dysfunction
      • Endothelial dysfunction and acute respiratory distress syndrome
      • Statins and cytokine storm
      • Statins and ebola
      • Statins and C-reactive protein
      • Statins and influenza
      • Statins and sepsis
      And there are probably other searches you could try.

      I have not read all of these articles (there are too many), but I have looked at some. It is a mixed bag in terms of both the quality of the studies and the conclusions. Some of the articles support the Fedson hypothesis, some do not. But my reading of this literature is that there is enough to support properly designed studies to ask if there is something here that could save lives in a viral pandemic.

      In particular, there is no large RCT that would directly address the question as to whether statin treatment in some form would reduce mortality in COVID-19.

      Finally, we get to the recent Lancet article that has been extensively commented on in this blog. If you haven’t read the actual article yet, I suggest you do. It is not behind a paywall — you can download the full paper. If you do, look at Figure 2 (titled “Independent predictors of in-hospital mortality”). You will see (with 95% confidence intervals) the predictors of mortality. As has been endlessly noted, the chloroquines are associated with increased mortality in this study. Associated with decreased mortality are ACE inhibitors and statins. Interestingly, there (as far as I can see) is only one other mention of the effect of ACE inhibitors and statins in this entire thread. I think this deserves more interest.

      I know less about ACE inhibitors (never worked with them) so have not commented on their effects (other than to cite the Lancet results), but Fedson likes the idea of ACE inhibitors and ARBs and mentions both in various publications along with statins.

      So, Nick, perhaps another straw to grasp. Better than HCQ? I don’t know. But at this point, there are some interesting hints. And there is the Lancet result.

      1. NICK says:

        Great info Robert
        As for statins and ACE inhibitors and ARBs. Their actions eventually lead down the same pathway for reducing oxidative stress in the epithelium. That is why I included anti-oxidant , especially SOD and GHS. They will do the same without side effects. If there was a way to get zinc in the cell with HCQ I am all for it. We have to keep thinking.

        1. NICK says:


    5. RA says:

      Like others, I don’t have the answers to your scenario. But I would definitely want my parents on a pulse ox and a low threshold to go to the hospital if things are getting worse. What I really want to know is if there is any benefit to early initiation of anti-platelet (i.e. aspirin) or anti-coagulation (i.e. enoxaparin) ..are we making a mistake by waiting until hospitalization, given the emerging evidence that some of COVID’s severe pathology involves clotting? I am skeptical any anti-viral will do a ton once already infected…an antiviral might have a role for pre/post exposure prophylaxis, however.

      I wonder if the best path is better outpatient monitoring and figuring out when and with what to anti-coagulate and immune modulate. Hopefully, in the coming weeks, we will get more data on the immune modulation front, but I don’t know if anyone is considering or studying early anticoagulation.

  62. NICK says:

    T cells found in COVID-19 patients ‘bode well’ for long-term immunity


      1. NICK says:

        You did , nice! I just came across it .

  63. JP Leonard says:

    For Big Data fans –
    Belgium has the world’s highest death rate from Covid, 800 per million according to Worldometer.
    Belgium has also banned HCQ outside of the hospital setting.
    Good luck, M. Macron.
    BTW back in the USA, Dr Ivette Lozano in Dallas made a couple interesting points on Youtube (speaking at a Reopen Texas rally on May 10).
    — the CDC keeps beating the same drum that there is no therapy for Covid19, so the parroting hospitals tell sick people to just stay home and wash their hands a lot. Which means infecting their families, and if they don’t get well on their own, then by the time the hospitals do take them in, they are in critical condition. FAIL.
    I think she’s giving patient the Zelenko 3 pack HCQ/Az/Zn.

    1. Ron says:

      Few things to mention:
      – The way Belgium count Covid deaths is different from most other countries, if you die with a cough you are likely to be recorded as a Covid death, with no testing required to validate it. This is why they also do not have an large statistical excess in unexplained non-covid deaths during covid outbreak timeframe, that most of other countries do.
      – Worldometer data is highly suspect, nobody can tell where it comes from.

    2. Robert Clark says:

      Thanks for the video link, J.P. She’s giving advice of Italian doctors in given HCQ early to prevent progression to severe disease:

      Key is to give the medication on *first sign* of symptoms, even before a positive test for COVID-19 comes in.

      Robert Clark

      1. psoun says:

        The original in vitro work in 2004 on SARS 1 suggested a fairly narrow treatment window. I am not sure why this wasn’t the first place we started to look (starting early) in trials. Starting later never seemed to have a base of evidence behind it ex-ante.

        1. It is mystifying why studies continue to be done on using HCQ on patients already under severe disease, when its proponents have stressed repeatedly that it has to be given early to be most effective. This desire to ONLY give it to patients already under severe disease is so strong among researchers that they are willing to claim a study is one on early use when it is actually also on patients already under severe disease.

          What’s even more mystifying and what I might say even incredible is top infectious disease experts including some who are considered the top ones in the nation don’t consider the difference important.

          Millions of peoples lives are at stake. The stakes are too high for such foolish and dangerous mistakes to be made.

          Robert Clark

  64. Edward R says:

    An Oxford University study of 950,000 patients using HCQ says it’s very safe.

    Why do so many including Fauci and others who should be well informed keep thinking otherwise?

    Your data please gentlemen.

    1. Martin (still not Shkreli) says:

      Calling it a “study on 950 000 patients” is misleading, it is a study of the medical history of 950 000 patients, over 14 databases, ie similar to what Derek presents.
      The conclusion concerns only HCQ at lower doses and over short times, and finds it rather safe (which is why it is in the pharmacopeia in the first place!)
      The lead investigator declares:
      “However, when prescribed in combination with azithromycin, it may induce heart failure and cardiovascular mortality and we would urge caution in using the two together.”
      “We lack data on the safety of hydroxychloroquine when used at higher doses, and it is too early to be able to understand its clinical effectiveness to treat COVID-19.”

      Hardly the unequivocal endorsement that your comment implies…

      1. Edward R says:

        I said study OF not On.

        Pharmacokinetics: Following a single 200 mg oral dose of PLAQUENIL to healthy males, the mean peak blood concentration of hydroxychloroquine was 129.6 ng/mL, reached in 3.26 hours with a half-life of 537 hours (22.4 days).

      2. Edward R says:

        Martin (still not Shkreli)

        Do the math if you can.

      3. Edward R says:

        It’s the Azithromycin that has the safety issues NOT HCQ.

        Read better next time and have a nice day!

  65. This is horrendous:

    Questions raised over hydroxychloroquine study which caused WHO to halt trials for Covid-19.

    The company that provided the data for the Lancet paper has been accused of falsifying data and Australia has denied ever supplying them with the information they claim comes from Australian hospitals.

    The company has refused to hand over their data. In view of the importance of this paper with randomized, controlled trials that could have finally determine the validity of HCQ’s effectiveness being cancelled, the authors should be required to either hand over their data or withdraw their paper.

    For me, red flags were already raised in that there were no experts on infectious disease among the authors. They were all either cardiologists or vascular surgeons. Then it is quite likely they didn’t even know suggesting a 48 hour limitation on treatment of patients means it is an “early use” study is flat out wrong.

    I don’t know what is worse suggesting incorrectly that it is an “early use” study or not knowing that it is not.

    Robert Clark

    1. NICK says:

      @Robert Thank you for posting this info first , I saw it much later from someone else.

  66. I personally think that the Lancetstudy is incredibly misleading and close to worthless, with respect to the primary endpoint of assessing potential benefit.

    Firstly, in the drug treatment arms, three times as many patients required ventilators. There is no obvious mechanism for HCQ/CQ to cause respiratory demcompensation or exacerbate the course of infection. The more likely explanation, which passes the Occam’s Razor test, is that patients selected for drug treatment were judged by their doctors to be at greater risk. This can’t be captured by the reported crude metrics of clinical condition used in the study.

    Secondly, the most obvious explanation for increased arrhythmias is that patients on these known arrythmogenic drugs were more likely to be placed on heart monitors. To my knowledge, no increase in deaths associated with cardiac arrhythmias were observed. The arrhythmia issue is always raised, but figuring out whether any of these actually causes fatalities is an elusive challenge. When rhythm disturbances are observed, presumably doses are withheld and then adjusted.

    The linked article makes the point that the prospective randomized controlled trials have trended to show benefit, while retrospective observational studies have trended to show harm.

    By far, the most useful study was the medrXiv preprint from NYU, showing a 44% reduced mortality to HCQ + Azithromycin + Zn compared to HCQ + Az without Zn. As there is no reason to suspect that HCQ + Az would accelerate respiratory disease or that there were fatal arrhythmias or than Zn would protect against fatal arrhythmias, Occam’s Razor indicates that HCQ + Az + Zn really did save lives.

    1. Questions says:

      Questions from the NYU study:

      Authors claim addition of zinc with an ionophore (HCQ) has a synergistic antiviral effect. Where is the PCR viral levels data demonstrating that effect in vivo with these patients since that was the basis for adding zinc in the first place? I suspect they were never measured post-diagnosis.

      Authors claim statistics show the addition of zinc sulfate was associated with decreased need for invasive ventilation. Indeed, there were 86 patients on ventilators in the no zinc group versus 33 in the zinc group. Ostensibly, they were all put on either treatment regimen on admission. What were the percentage of deaths that were on mechanical ventilation in both groups and how long post admission was that ventilation started in both groups? That should be information they definitely have. Antiviral/antimicrobial therapy doesn’t work in a few hours except in Hollywood movies. (If Dr. Who went back in time with his Tardis and gave triple combination HIV therapy to all patients in ICU and hospice dying of AIDS, they still would have died albeit with somewhat lower viral titers. It takes months to get to undetectable levels.)

      Other notes: Their reference is for research showing that chloroquine is a zinc ionophore. Hydroxychloroquine is not chloroquine and it is not metabolized to chloroquine. They are two distinct chemical entities and they are both N-dealkylated leaving two chemically distinct metabolites. They have multiple references that seem to infer that these are identical drugs. They are not. And I would not infer that the ability of either drug to serve as an ionophore for zinc or that the synergistic ability of that the antiviral activity with separate drugs used on a different corona virus in a different cell line etc. is a rigorous claim to anything.

      Both the Lancet study and the NYU study are retrospective. They both highlight the need for prospective studies as they raise interesting questions. Maybe someone should even design studies where they compare chloroquine versus hydroxychloroquine since the medical establishment, media and government agencies seem to think them interchangeable. Given the infection levels in the U.S., rampant stupidity of the US government’s response to this virus and the rampant stupidity of the US populace, I doubt that we will run out of patients for such studies anytime soon.

    2. OC says:


      The Lancet “study” is so flawed as to be utterly useless. If Derek had any intellectual integrity he would add to this opinion piece the recent SUBSTANTIAL concerns about the issues with this study:

      The authors have not shared their data, it is therefore unverifiable and non-replicable. Where is Derek’s concern about that little issue?

      Why are there only FOUR authors on thing? How is that even possible?

      Where is the adjustment to ensure HCQ had time to work? I.e. Most studies only include patients on a course of drugs for more than one or two days? If sicker patients on their death beds were given the drugs and died within hours they are still included in this study.

      Where is Derek’s concern at the curious Australian data where 73 patients were said to have died across 5 hospitals by April 21st? This despite TOTAL Australian deaths not even being 73 by that date, many deaths having been in nursing homes not hospitals and deaths being across MANY more than 5 hospitals (probably 5 in Sydney alone that I can think of)?

      My suspicions are that this is a garbage in, garbage out study.

  67. JP Leonard says:

    The new study by Raoult presents its conclusions thus:
    “Treatment with HCQ-AZ was associated with a decreased risk of transfer to the ICU or death (HR 0.19 0.12-0.29), decreased risk of hospitalization ≥10 days (odds ratios 95% CI 0.37 0.26-0.51) and shorter duration of viral shedding (time to negative PCR: HR 1.27 1.16-1.39).”
    What is HR? Could someone be so kind to explain these numbers? It will be hard to tease it out of google with only a two-letter abbreviation. It looks like they are some kind of statistics, the first number could be the mean followed by a range. Does he say how much decreased by?
    CI could be confidence interval.
    Anyway not much joy for me there, no percentage shown for the reduction and no zinc 🙂

    1. Some idiot says:

      Not my field, but HR is Hazard Ratio, which is a way of comparing two groups. Wikipedia has a bit on it, and after reading that you will be significantly better on it than I! 🙂

  68. NICK says:

    The push behind remdesivir and MD in the government link to Gilead. Follow the money!
    Hydroxychloroquine = cheap generic drug that has be used from more than a half a century.
    Watch the video if interested it only 9min.

    1. Edward R says:

      How is this even possible?!!!

      The NIH COVID19 Treatment Guidelines Panel membership is absolutely LOADED with ‘experts’ having financial ties to Gilead the maker of Remdesivir.

      Everyone needs to see this video before it gets taken down. The ‘smoking gun’ occurs about 8 minutes in for those short on time.


      Where’s Derek?

      1. Derek Lowe says:

        I’m right here. Do you have an argument about the clinical data?

        1. Edward R says:

          Thanks Derek,

          Have you seen the news report outlining that the vast majority of panel members have or have had financial ties to Gilead?

          Can you tell us if this is normal?

          Also what are your thoughts on the opinions expressed in the interview?

          Thanks for your response. This is something that needs to be addressed to see if it IS or IS NOT an issue that needs to be investigated further.

  69. NICK says:

    Latest interview from Dr. Zelenko and info on clinical trial results coming in 10 days or so.

    1. Edward R says:

      At 10:45 into the interview Zelenko speculates (only speculates) that Fauci and his ‘experts’ may have intentionally sought the outcome of shutting down the US economy.

      If that SPECULATION proves correct then treason charges will have to be paid on all of those involved in this ongoing fiasco.

      Here’s to hoping that mere incompetence or financial gain ONLY is at play.

      1. David Young MD says:

        Well, I cannot agree with what Dr. Zelenko says.. not on any thing, really. Let me tell you, as a physician I have understood that it is very easy to get off track. It is very easy to think that you have a better treatment than anyone else… something that you thought up yourself. It turns out it is easy to think that a number of your patients did exceptionally well because of what you did, and not realize that it was by chance alone. Patients with lung cancer, for instance may die in 2 months or live for 4 years, depending upon a lot of factors. If I were “lucky” enough to get 4 patients in a row who had a milder form of the disease, and they lived 3 years rather than 1 year, I would be tempted to think that it was because of the “special” treatment that I gave, even though it was just “luck” that those 4-in-a-row had milder disease. In fact, over a doctor’s career, it would be impossible, I think, that by chance alone I would “think” that I had a special treatment for a certain disease. As a smart physician, I have learned that one needs randomized, blinded studies to know for sure.

        If Hydroxychloroquine is as good as they say, then there should be hundreds and hundreds of physicians telling us that it is that good. And the studies should all look very good. Not the negative study mentioned in this blog post.

        And curse the person who thinks that there is just some conspiracy theory that downplays Hydroxychloroquine for their monetary good. Look, Fauci can get Covid19 and suffer and die. So can his wife, his brother, his kids. There is no way that he would conspire against a successful treatment. Anyone who thinks so has a sick mind.

        Nevertheless, there are still over 100 studies worldwide on Hydroxychloroquine. Many of these are randomized. A few include zinc supplementation. About a dozen are using Hydroxychloroquine as a preventative. Several of these studies should be completed in the next 4 weeks. We will know more before long.

        1. NICK says:

          Most physician are on “caterpillar line” – will walk in line one after the other an go in circles till they die. They are not allowed to think anymore. They never even touch the patient, they only look at the labs. They are afraid to step out of line for the fear of being looked down upon by their peers. If a pt dies in care of the physician and the physician is following the protocol for standard of care there are no questions asked but the slightest variation from the standard of care and they are targets of lawyers. Physicians are in a tough spot, most care for their patients and do have their safety in mind but the other reasons I states supersede all other reasons. Most great leaps forward are made by accidentally discovery, form a person from a completely different field of study or a renegade thinker from the same field of study. Only incremental change is possible with incremental thinking is pursued in the continuum. Just an observation and no offense to an Physicians.

        2. Robert Clark says:

          Perhaps the evidence is there if we are willing to put together the clues:

          Researchers ponder why covid-19 appears deadlier in the U.S. and Europe than in Asia.

          Graphic showing radically reduced death rates in Asian countries:


          National Consumption of Antimalarial Drugs and COVID-19 Deaths Dynamics : an Ecological Study.
          “COVID-19 (Coronavirus Disease-2019) is an international public health problem with a high rate of severe clinical cases. Several treatments are currently being tested worldwide. This paper focuses on anti-malarial drugs such as chloroquine or hydroxychloroquine, which have been currently reviewed by a systematic study as a good potential candidate and that has been reported as the most used treatment by a recent survey of physicians. We compare the dynamics of COVID-19 death rates in countries using anti-malaria drugs as a treatment from the start of the epidemic versus countries that do not, the day of the 3rd death and the following 10 days. We show that the first group have a much slower dynamic in death rates that the second group.”

          Here’s the key graphic showing radically reduced death rates in those countries using the antimalarials:


          WORLD NEWS MARCH 12, 2020 / 9:51 AM
          South Korea experts recommend anti-HIV, anti-malaria drugs for COVID-19
          Elizabeth Shim
          “The groups advised discretion among medical professionals, while recommending the administration of Kaletra, an anti-HIV medication that includes the drugs lopinavir and ritonavir.
          Kaletra blocks the ability of HIV to replicate itself, and also inhibits the growth of cancer cells.
          South Korean experts are also recommending the use of hydroxychloroquine in combination with the anti-HIV medication. HCQ is sold under the brand name Plaquenil, among others, and is used for the prevention and treatment of malaria.”

          Treatment Response to Hydroxychloroquine, Lopinavir/Ritonavir, and Antibiotics for Moderate COVID 19: A First Report on the Pharmacological Outcomes from South Korea.
          “Conclusion: This first report on pharmacological management of COVID 19 from South Korea revealed that HQ with antibiotics was associated with better clinical outcomes in terms of viral clearance, hospital stay, and cough symptom resolution compared to Lop/R with antibiotics or conservative treatment. The effect of Lop/R with antibiotics was not superior to conservative management. The adjunct use of the antibiotics may provide additional benefit in COVID 19 management but warrants further evaluation.”


          Indonesia to keep prescribing two malaria drugs for COVID-19 despite bans in Europe.
          *“The world’s fourth-most populous nation has since late March recommended that chloroquine and its derivative, hydroxychloroquine, be widely administered, including to coronavirus patients with moderate to severe symptoms, according to Food and Drug Monitoring Agency guidelines.”*


          India Promotes Hydroxychloroquine, as WHO Stops Trials Over Safety Issues
          BY AILA SLISCO ON 5/26/20 AT 7:42 PM EDT


          Commentary on “Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open label non-randomized clinical trial” by Gautret et al.
          Mondher Toumi & Samuel Aballea
          Journal of Market Access & Health Policy, 8:1, 1758390, DOI:10.1080/20016689.2020.1758390

          “Hydroxychloroquine treatment with massive testing and limited confinement has successfully worked in South Korea to control the outbreak with an impressively low rate of fatalities[44].”

          “So far, European decision-makers have shown very little ability to learn from China [45] and South Korea [44], the only two countries that have been able to control the outbreak. Cultural differences, language barriers, and arrogance from the old Europe may cer- tainly explain why best practice knowledge sharing failed in this situation.”

          Robert Clark

  70. john says:

    After listening to this latest interview with Dr. Zelenko, and his mention of quercetin, I became curious as to what effect quercetin might have on the QT interval. Quercetin does have some effect on cardiac ion channels and may be a cardiac vasodilator, apparently.

    As far as I could find, quercetin does not prolong QTc, and at least in mice isolated hearts, it might shorten QTc! Now, I think that the zinc ionophore theory is just one mechanism whereby HCQ might affect coronaviruses, so, not sure that quercetin is a reasonable substitute for HCQ. Still, quercetin might work.

    What I found that to be interesting and something I had not known is, that apparently grapefruit juice can prolong the QT interval!

    Now, the study linked above, participants really had to chug a fair amount of it (up to 2 L!), but the prolongation of the QT interval was not trivial. The net prolongation amount was 14.0 ms, and statistically significant — more than twice the amount of non-significant QT prolongation in COVID-19 patients treated with HCQ in the Mercuro study published in JAMA cardiology. Another grapefruit juice study found a prolongation of 10 msec after drinking only 1L of grapefruit juice:

    So, I believe it’s incumbent on the FDA now to issue a health warning to the public about the potential hazards of drinking this dangerous juice!

    1. NICK says:

      Green Tea Extract will also work as Zn inophore. You can take Quercetin in combination with Green Tea Extract with zinc. This is at onset.
      You add super oxide dismutase and glutathione if symptoms worsen.

      1. john says:

        Please be careful with green tea extract. It can cause severe liver damage, even to the point of requiring liver transplantation.

        I would never take this.

      2. john says:

        Just to drive the point home about the dangers of green tea extract re liver failure:

        A similar fate befell a friend of ours. The person involved was a nurse who was very concerned about her health. After taking green tea extract, she had liver failure, requiring transplantation, and is now deceased, unfortunately, at a relatively young age. This is not just a theoretical risk.

        1. NICK says:

          @John appreciate the info. Really sorry for your loss! From what I know it above 800mg and most supplements are around 300mg per day. But will keep your warning in mind. Once again thank you.

      3. Important question says:

        Do we snort the green tree extract or do we smoke it? Or is it best to speed absorption through rectal administration? What drug delivery method do you recommend? I’m assuming we don’t try to reconstitute by making tea out of it, correct? Is there a food effect for an oral route? Can I have a biscuit with my green tea extract? What doses do you recommend for myself or someone like my mother who is in a nursing home? She has slightly impaired renal function as is normal for her age so should we adjust those doses for renal excretion of putative active ingredients? I don’t want you to hold my hand but I searched exhaustively and I’m not enough of a “renegade thinker” to come up with those doses or routes of administration on my own. I searched for the published data but could not find that clinical data published as of yet since this a relatively new virus and all.

        1. NICK says:

          Obviously you are not a thinker let alone a renegade thinker . I am not also neither. I am just a troll.

    2. Grumpy Old Professor says:

      “only” a litre? My mouth is puckering and my teeth are dropping out at the thought….. 🙂

  71. Dave McCann says:

    Such a BS article, especially in light of the recent Yale study added to several other showing positive results.

  72. EugeneL says:

    This is not to say that HCQ works in later stages, it likely does not. Although HCQ may well work in the early stages when the virus is still taking grounds.

    The study increasingly looks like it was cooked:

    If you can refute some arguments in the video please do. But the key principle of research studies should always hold: a study needs to be verifiable. The HCQ article in question is NOT. After significant worries were raised about mistakes in the data, the community, or even select auditors, do not have capability to go and recheck the claims.

    1. NICK says:

      Thank you for the link to video.

  73. SALEH says:

    Let’s have a look at the boarder image in an ethical approach with a sense of reality
    There is conflicting results concerning HCQ and CQ and we are waiting for more robust data from hoped RCT.
    But the time those RCT comes out many persons will have died and I am afraid that those RCT would yield conflicting results as its frequently observed (hope not of course)
    The main point:
    Most exposed persons are those over 50 or less with co-morbidities.
    It’s an infectious disease that is rapidly killing a lot of persons in this group.
    This group of person have to be and be given a chance to survive based on available medications based on current cumulative knowledge (not placebo) even if those medications have only a presumption of efficacy. ( I am talking here about all available products ,not only about HCQ)
    In that perspective, Russian roulette of a trial is not an option here

  74. NICK says:

    “Open letter to MR Mehra, SS Desai, F Ruschitzka, and AN Patel, authors of“Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis”. Lancet. 2020 May 22:S0140-6736(20)31180-6. doi: 10.1016/S0140-6736(20)31180-6. PMID: 32450107and to Richard Horton (editor of The Lancet).Concerns regardingthe statistical analysis and data integrityThe retrospective, observational study of 96,032 hospitalized COVID-19 patients from sixcontinents reported substantially increased mortality (~30% excessdeaths) and occurrence of cardiac arrhythmias associated with the use of the 4-aminoquinoline drugs hydroxychloroquine and chloroquine. These results have had a considerable impact on public health practice and research. The WHO has pausedrecruitment to the hydroxychloroquine arm in their SOLIDARITY trial.The UK regulatory body, MHRA,requested the temporarypausing of recruitment intoall hydroxychloroquine trials in the UK (treatment and prevention), andFrance has changed its national recommendation for the use of hydroxychloroquine in COVID-19 treatmentand also halted trials.The subsequent media headlines have caused considerable concern to participants and patients enrolled in randomized controlled trials (RCTs) seeking to characterizethe potential benefits and risks of these drugsin the treatment and prevention ofCOVID-19 infections. There is uniform agreement that well conducted RCTs are needed to inform policies and practices.This impact has led many researchers around the world to scrutinize in detail the publication in question. This scrutinyhas raised both methodological and data integrity concerns. The main concerns are listed as follows:1.There wasinadequate adjustment for known and measured confounders (disease severity, temporal effects, site effects, dose used).2.The authors have not adhered to standard practices in the machine learning and statistics community. They have not releasedtheir code or data. There is no data/code sharing and availability statement in the paper. The Lancet was among the many signatories on the Wellcome statementon data sharing for COVID-19 studies.3.There was noethics review.4.There was no mention of the countries or hospitals that contributed to the data sourceandno acknowledgments to their contributions.A request to the authors for information on the contributing centres was denied.5.Data from Australia are not compatible with government reports (too many cases for just five hospitals, more in-hospital deaths than had occurred in the entire country during the study period). Surgisphere (the data company) have since statedthis was an error of classificationof one hospital from Asia.Thisindicates the need for further error checking throughout thedatabase.6.Data from Africa indicate thatnearly 25% of all COVID-19 cases and 40% of all deaths in the continentoccurred in Surgisphere-associated hospitals which had sophisticated electronic patient data recording, and patient monitoring able to detect and record “nonsustained [at least 6 secs] or sustained ventricular tachycardia or ventricularfibrillation”. Both the numbers of cases and deaths, and the detailed data collection, seem unlikely.7.Unusually small reported variances in baseline variables, interventions and outcomes between continents(Table S3).
    8.Mean daily doses of hydroxychloroquine that are 100 mg higher than FDA recommendations, whereas 66% of the data are from North American hospitals.9.Implausible ratios of chloroquine to hydroxychloroquine use in some continents10.The tight 95% confidence intervals reported for the hazard ratios are unlikely. For instance,for the Australiandatathis would need about double the numbers of recorded deathsas were reported in the paper.The patient data have been obtained through electronic patient records and are held by the US company Surgisphere. In response to a request for the data Professor Mehra has replied; “Our data sharing agreements with the various governments, countries and hospitals do not allow us to share data unfortunately.”Given the enormous importance and influence of these results, we believe it is imperative that:1.The company Surgisphereprovides details on data provenance. At the very minimum, this means sharing theaggregated patient data at the hospital level (for all covariates and outcomes)2.Independent validation of the analysis is performed by a group convened by the World Health Organization,or at least one other independent and respected institution. This would entail additional analyses (e.g. determining if there is a dose-effect)to assess the validity of the conclusions3.There is openaccess to allthe data sharing agreements cited above to ensure that,in each jurisdiction,any mined data was legally and ethically collected and patient privacy aspects respectedIn the interests of transparency, we also ask The Lancet to make openly available the peer review comments that led to this manuscript to be accepted for publication.This open letteris signed by clinicians, medical researchers, statisticians, and ethicistsfrom across the world. The full list of signatoriesand affiliationscan be found below.
    List of SignatoriesDr James Watson (Statistician, Mahidol Oxford Tropical Medicine Research Unit, Thailand)1Professor Amanda Adler (Trialist & Clinician, Director of the Diabetes Trials Unit, UK)DrRavi Amaravadi (Researcher,University of Pennsylvania, USA)Dr Ambrose Agweyu (Medical researcher, KEMRI-Wellcome Trust Research Programme, Kenya)Professor MichaelAvidan(Clinician, Washington University in St Louis, USA)Professor Nicholas Anstey (Clinician, Menzies School of Health Research, Australia)Dr Yaseen Arabi (Clinician, King Saud Bin Abdulaziz University for Health Sciences, Saudi Arabia)Dr Elizabeth Ashley (Clinician, Director of the Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit, Laos) Professor Kevin Baird (Researcher, Headof the Eijkman-Oxford Clinical Research Unit, Indonesia)Professor Francois Balloux (Researcher, Director of the UCL Genetics Institute, UK)Dr Clifford George Banda (Clinician, University of Cape Town, South Africa) Dr Edwine Barasa(Health economist, KEMRI-Wellcome Trust Research Programme, Kenya) Professor Karen Barnes (Clinical Pharmacology, University of Cape Town, South Africa)Professor David Boulware (Researcher& Triallist, University of Minnesota, USA)Professor Buddha Basnyat (Clinician, Head of the Oxford University Clinical Research Unit -Nepal, Nepal)Professor Philip Bejon (Medical researcher, Director of the KEMRI-Wellcome Trust Research Programme, Kenya)Professor Mohammad Asim Beg(Clinician/Researcher, Aga Khan University,Pakistan)Professor Emmanuel Bottieau (Clinician, Institute of Tropical Medicine, Antwerp, Belgium)Dr Sabine Braat (Statistician, University of Melbourne, Australia)Professor Frank Brunkhorst (Clinician, Jena University Hospital, Germany)Dr Todd Campbell Lee (Researcher, McGill University, Canada)Professor Caroline Buckee (Epidemiologist, Harvard TH Chan School of Public Health, USA)Dr James Callery (Clinician, Mahidol Oxford Tropical Medicine Research Unit, Thailand)Professor John Carlin (Statistician, University of Melbourne & Murdoch Children’s Research Institute, Australia)Dr Nomathemba Chandiwana (Research Clinician, University of the Witwatersrand, South Africa)Dr Arjun Chandna (Clinician, Cambodia Oxford Medical Research Unit, Cambodia)Professor PhaikYeong Cheah (Ethicist/Pharmacist, Mahidol Oxford Tropical Medicine Research Unit, Thailand)Professor Allen Cheng (Clinician, Monash University, Australia)Professor Leonid Churilov (Statistician, University of Melbourne, Australia)Professor Ben Cooper (Epidemiologist, University of Oxford, UK)Dr Cintia Cruz (PaediatricianMahidol Oxford Tropical Medicine Research Unit, Thailand)Professor Bart Currie (Director, HOT NORTH, Menzies School of Health Research, Australia)Professor Joshua Davis (Clinician, President of the Australasian Society for Infectious Diseases, Australia)Dr Jeremy Day (Clinician, Oxford University Clinical Research Unit, Vietnam)Professor Nicholas Day (Clinician,Director of the Mahidol Oxford Tropical Medicine Research Unit, Thailand)Dr Hakim-Moulay Dehbi (Statistician, University College London, UK)Dr Justin Denholm (Clinician, Researcher, Ethicist, Doherty Institute, Australia)DrLennie Derde (Intensivist/Researcher, University Medical Center Utrecht, The Netherlands)Professor Keertan Dheda (Clinician/Researcher, University of Cape Town,& Groote Schuur Hospital, South Africa)Dr Mehul Dhorda (Clinical Researcher, Mahidol Oxford Tropical Medicine Research Unit, Thailand) Professor Annane Djillali (Dean of the School of Medicine,Simone Veil Université,France)Professor Arjen Dondorp (Clinician, Mahidol Oxford Tropical Medicine Research Unit, Thailand)Dr Joseph Doyle (Clinician, Monash University and Burnet Institute, Australia)Dr Anthony Etyang (Medical Researcher, KEMRI-Wellcome Trust Research Programme, Kenya)Dr Caterina Fanello (Epidemiologist, University of Oxford, UK)Professor Neil Ferguson (Epidemiologist, Imperial College London, UK)ProfessorAndrew Forbes (Statistician, Monash University, Melbourne, Australia)Professor Oumar Gaye (Clinical Researcher, University Cheikh Anta Diop, Senegal)Dr Ronald Geskus (Head of Statistics at theOxford University Clinical Research Unit, Vietnam)Professor Dave Glidden(Biostatistics, University of California, USA)Professor Azra Ghani (Epidemiologist, Imperial College London, UK)Prof Philippe Guerin (Medical researcher, University of Oxford, UK)Dr. Raph Hamers (Clinician/Trialist, Eijkman-OxfordClinical Research Unit, Indonesia)Professor Peter Horby (Clinical Researcher, Centre for Tropical Medicine and Global Health, University of Oxford)DrJens-Ulrik Jensen (Clinician/Trialist, University of Copenhagen, Denmark)Dr Hilary Johnstone (Clinical Research Physician, Independent)Professor Kevin Kain (Clinical Researcher, University of Toronto, Canada)Dr Sharon Kaur (Ethicist, University of Malaya, Malaysia)1For correspondence:
    Dr Evelyne Kestelyn (Head of Clinical Trials, Oxford University Clinical Research Unit, Vietnam)Dr Tan Le Van (Medical Researcher,Oxford University Clinical Research Unit, Vietnam)ProfessorKatherine Lee (Statistician, University of Melbourne, Australia)Professor Laurence Lovat (Clinical Director of Wellcome EPSRC Centre for Interventional & Surgical Sciences, UCL, UK)Professor Kathryn Maitland (Clinician, Imperial College London/KEMRI Wellcome Trust Programme, Kenya)Dr Julie Marsh (Statistician, Telethon Kids Institute, Australia)Professor John Marshall (Clinician/Researcher,University of Toronto, Canada)Dr Gary Maartens (Clinician, University of Cape Town, South Africa)Professor Mayfong Mayxay (Clinician/Researcher, Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit, Laos)Dr John McKinnon(Clinician/Researcher, Wayne State University, USA)Dr Laura Merson (Clinical researcher, University of Oxford, UK)Dr Alistair McLean (Medical researcher, University of Oxford, UK)Professor Ramani Moonesinghe(Clinician researcher, UniversityCollege London, UK)Professor Bryan McVerry (Medical researcher, University of Pittsburgh, USA)Professor William Meurer (Clinician/Medical researcher, University of Michigan, USA)Dr Kerryn Moore (Epidemiologist, London School of Hygiene and Tropical Medicine, UK)Dr Rephaim Mpofu (Clinician, University of Cape Town, South Africa) Dr Mavuto Mukaka (Statistician, Mahidol Oxford Tropical Medicine Research Unit, Thailand) Dr SrinivasMurthy (Clinical Researcher, University of British Columbia, Canada)Professor Kim Mulholland (Clinician, London School of Hygiene &Tropical Medicine, UK)Professor Alistair Nichol (Clinician Researcher, Monash University, Australia)Professor Francois Nosten (Clinician, Director of the Shoklo Malaria Research Unit, Thailand)Dr Matthew O’Sullivan (Clinician, Westmead Hospital & University of Sydney, Australia)Professor Piero Olliaro (Clinical Researcher, University of Oxford, UK)ProfessorMarie Onyamboko (Clinical researcher, Kinshasa School of Public Health, DRC)Dr Marcin Osuchowski (Medical researcher, Ludwig Boltzmann Institute, Austria)Professor Catherine Orrell (ClinicalPharmacologist, University of Cape Town, South Africa)ProfessorJean Bosco Ouedraogo (Medical Researcher, WWARN, Burkina Faso)DrElaine Pascoe (Statistician, University of Queensland, Australia)Professor David Paterson (Clinician, Director, UQ Centre for Clinical Research, Australia)Dr Kajaal Patel (Paediatrician, Cambodia Oxford Medical Research Unit, Cambodia)Dr Tom Parke(Statistician, Berry Consultants, UK)ProfessorPhilippe Parola (Researcher, Aix-Marseille University, France)Professor Paul Newton (Clinician, University Oxford, UK)Professor David Price (Statistician, Doherty Institute & University of Melbourne, Australia)Professor Richard Price (Clinician,Menzies School of Health Research, Australia)Professor Sasithon Pukrittayakamee (Clinician, Mahidol University, Thailand)Dr Ben Saville (Statistician, Berry Consultants & Vanderbilt University)Professor Jason Roberts (Pharmacist/Clinician, The University of Queensland, Australia) Professor Stephen Rogerson (Clinician, University of Melbourne, Australia)Professor Kathy Rowan (Researcher, Director of the ICNARC Clinical Trials Unit, UK)Dr William Schilling (Clinician, Mahidol Oxford Tropical Medicine Research Unit, Thailand)Dr Anuraj Shankar(Clinician/Trialist, Eijkman-OxfordClinical Research Unit, Indonesia)Professor Sanjib Kumar Sharma (Clinician, Koirala Institute of Health Sciences, Nepal)Professor Julie Simpson (Statistician,University of Melbourne, Australia)Professor Frank Smithuis (Clinical researcher, Director of the Myanmar Oxford Tropical Research Unit, Myanmar)Dr Tim Spelman (Statistician, Burnet Institute, Australia) Dr Kasia Stepniewska (Statistician, University of Oxford, UK)Dr Nathalie Strub Wourgaft (Clinician, Drugs for Neglected Diseases initiative, Switzerland)Dr Aimee Taylor (Statistician, Harvard T.H. Chan School of Public Health, USA)DrWalter Taylor (Clinician, Mahidol Oxford Tropical Medicine Research Unit, Thailand)Professor Guy Thwaites (Clinician, Director of the Oxford University Clinical Research Unit, Vietnam)Professor Tran Tinh Hien (Clinician, Oxford Clinical Research Unit, Vietnam)Professor Steven Tong (Clinician, University of Melbourne, Australia)Professor Paul Turner (Clinician/Researcher, Director of Cambodia Oxford Medical Research Unit, Cambodia)Professor Ross Upshur(Head ofDivision of Clinical Public Health, University of Toronto, Canada)Professor Rogier van Doorn (Clinical Microbiologist, University of Oxford, UK)Professor Sir Nicholas White (Clinician,Mahidol Oxford Tropical Medicine Research Unit, Thailand)Professor Thomas Williams (Clinician, KEMRI-Wellcome Trust Research Programme, Kenya)Professor Chris Woods (Researcher, Duke University, USA)Dr Sophie Yacoub (Clinician, Oxford University Clinical Research Unit, Vietnam)Professor Marcus Zervos(Researcher, Wayne State University School of Medicine, USA”

    1. WustlMed says:

      Totally agree. This is worse than the VA one. Too much politics

  75. NICK says:

    An open letter to Mehra et al and The Lancet – search in google. I tried posting the link but didn’t work

  76. Milord Cutter says:

    The second the Impeached Imbecile uttered the word hydroxychloroquine the entire world should have known this was a total scam.

  77. David Young MD says:

    As a physician (oncologist), I beg to differ… at least for myself. (although I do see what you say in many other physicians). I am willing to go out on a limb, when I give proper informed consent. At least 10 times in my career I gave high dose Artemisinin for patients with advanced cancer for which any reasonable conventional treatments were exhausted. (That was back in the day… I would not do it now, because I observed that high doses of herbal Artemisinin had no side effects and did absolutely no good, making me think that the patient was not absorbing it.). I understand medicinal chemistry a lot better now having read this blog for the past 10 years, along with a few other blogs. It has given me a slight edge as a physician. It has also taught me to be humble. There were a few times that I thought I had a better treatment for a certain cancer… only to later observe that I was just lucky.

    I don’t walk a Caterpiller line. Don’t create straw dogs to cut down.

    And speaking of Quercetin….. Isn’t Quercetin a PAINS?

    1. NICK says:

      Glad to see you are a very different type of physician and I thank you for not walking in the line.

    2. anon the II says:

      Yes, Quercetin is a PAINS compound. My rule of thumb is that if I see a publication where someone has discovered quercetin as something useful, I don’t read the article and make a note to never read anything from that author again. Ever. Life’s too short.

  78. EugeneL says:

    It looks like Derek has focused his victory post on an aricle that later turned out to be based on fabricated data

    1. EugeneL says:

      More character destruction:
      “Court records in Cook County, Illinois, show that Desai is named in three medical malpractice lawsuits filed in the second half of 2019”

      The company behind the data is really dodgy:

      “No items appears to be older than March 2020 on the website or their linkedin Page. D&B lists two employees and under $50K income. And they claim to have a database of 96,032 COVID-19 patients from 671 hospitals in six continents?”

      1. loupgarous says:

        If being named as a defendant in a medical malpractice action disqualifies a physician, babies would have be delivered exclusively by midwives, and cardiology would be a specialty with no practitioners outside countries with British-style litigation rules (where losers in well-defended malpractice suits pay both sides’ costs and those of the Court).

        Medical misadventures happen frequently in those and other medical specialties. Unless binding arbitration is available as a remedy, litigation is the only venue available to determine whether someone’s medical injuries stem from unavoidable medical risks or from unacceptable departures from the standard of care. So, again, let’s stick to the facts, not the innuendo.

    2. blogreader01 says:

      Oh my. That is rich.

      Lord, save us from the harm caused by these anti-Trump losers and their pathetic, unfounded biases.

      1. john says:

        Still more on problems with Surgisphere and the Lancet paper here.

    3. john says:

      More here on the possibly false nature of the data in the Lance paper:

      If this critique is true, this will be one of the greatest scandals in medical research. I feel sorry for Mandeep Mehra, the primary author, who appears to be a very established and well-regarded researcher.

      Makes me angry that I was, even if temporarily, taken in by this. More damaging is the fact that this study, if false, led to regulatory agencies militating against early use of HCQ, the halting or suspension of ongoing trials, etc. If HCQ does work in an outpatient setting, and I suspect that David Boulware’s Univ. Minnesota’s RCTs may well show positive results, this Lancet study may turn out to have caused real harm to a large number of patients.

      Derek, perhaps you would like to comment?

      1. Tony M says:

        For what it is worth, some comments on the Lancet Research Report:

        Some people have commented that the chloroquine/hydroxychloroquine treatment groups were more severely ill when compared to the control group with some making reference to different levels of mechanical ventilation required with the control group requiring just 7.7% while the study treatment groups required between 20.0% and 21.6%. This is correct and can best be demonstrated when you look at the 1,102 patients who were excluded from the analysis because they were already on mechanical ventilation when treatment was commenced. If you add these back to 14,888 treatment group, they represent 6.9% of the total unadjusted group. The 6.9%s is nearly equal to the total of 7.7% in the Control Group. As none of these 1.102 patients required mechanical ventilation, as a result of receiving chloroquine/hydroxychloroquine, it can only mean that the treatment groups were more severely ill than the control group. This was not a Randomly Controlled Trial (RCT). Hence the prescribing of the treatment drugs really represents an indicator of severity of the patients as well as a treatment for the illness.

        In other words, the prescribing of Chloroquine/hydroxychloroquine represents an indicator of severity in patients, just like the “SPO2 < 94%” is also an indicator of severity, with those having a low level of SPO2 been provided with oxygen. If you take the hypothetical case of say 100% of patients with a SPO2 94% did not receive oxygen, no exceptions, and replaced “Oxygen Supply” in the analysis for “SPO2<94%”, then when you analysed this data, you would get the same Hazard Risk factor for “Oxygen Supply” as was calculated for “SPO2<94%”. All you are doing is relabelling the variable in the analysis. However, from Figure 2, this would indicate an increased risk of in-hospital mortality for “Oxygen Supply” with a Hazard Ratio of 1.664. Obviously. this is a ridiculous result as oxygen use is only given to the more severe ill patients. However, this example does highlight that, when you don’t have a RCT, a higher risk of mortality for a particular treatment may really be an indication of severity, as assessed by the doctor etc, as opposed to any negative effects of the drug.

        If you take this line of thinking that the control group may have been less severely affected compared to the treatment group, is there any other information that may indicate they had milder versions of the illness? The paper indicates that 38,927 or 40.5% of patients received antivirals. No mention was made of any other treatments for Covid-19. Is it possible that for those patients that did not receive antivirals, even though they were in hospital, their condition was so mild that no specific treatment for Covid-19 was given that was worth mentioning? I don’t know. However, if you were to exclude them from the machinal ventilation, mortality and ventilator and mortality percentages, you could get percentages of 19.0%, 22.7% and 32.6% which are comparable to the treatment groups (ie. Mechancial Ventilation of 19.0% = 7.7% / .405, Mortatility of 22.7% = 9.3% / .405 and Ventilator or Mortality of 32.6% = 13.2% / .405 ).

        If 59.5% of the Control Group had only a mild illness, then the statistical analysis of any treatment for any drug provided to the more severely ill patients would most likely always indicate an increased risk of in-hospital mortality when compared a control group that included them. This then raises the question, what were the result for those patients who received the Antivirals? Did the analysis show they had an increased risk? How did this risk compare to that for Chloroquine/Hydroxychloroquine or the hypothetical “Oxygen Supply” example ( ie. SPO2 < 94%)? Unfortunately, a review of Figure 2 of the research report indicates that Antivirals were not measured in the risk factors measured for mortality but they were included in the risk factors measured for ventricular arrhythmias in Figure 3. Why were these excluded from Figure 2? They would have been both very interesting and possibly meaningful when used as a comparison. I have a hunch they were excluded because, if prescribing antivirals is also an indication of severity of illness in patients, they probably indicated similar increased risk of in-hospital mortality as those found for Chloroquine/Hydroxychloroquine!
        After fixing for data errors etc, it would be good if the authors of this report also included an analysis of risk of in-hospital mortality for the antivirals as well as the Chloroquine/Hydroxychloroquine Treatment groups. A more valid comparison can then be made. However, differences in severity in treatment groups could still distort this analysis.

        1. Robert Clark says:

          Thanks for that insightful analysis. This provides further reason why the original numbers, not just their “adjusted” numbers, must be provided so an independent analysis can be made.

          Robert Clark

  79. JP Leonard says:
    A few years ago the British medical journal, The Lancet, published a paper touting the safety of HCQ. But this was before HCQ with zinc was found effective if used earlier enough against Covid-19. Covid-19 turned HCQ’s effectiveness into a big problem for Big Pharma’s big profits. Part I

    1. loupgarous says:

      “Covid-19 turned HCQ’s effectiveness into a big problem for Big Pharma’s big profits.

      2 problems with that analysis:
      – HCQ doesn’t seem to have any detectable effectiveness on studies with large treatment cohorts. In the largest (671 hospitals) study so far, more people die when they are given HCQ in “in time to do any good” than people on “standard of care” treatment.
      – Gilead Sciences and other antiviral manufacturers aren’t going to be turning big profits on a drug for COVID-19 until they can demonstrate safety and efficacy, which hasn’t (that I’m aware) happened yet.

      So, let’s stick to facts, please.

  80. JC James says:

    Gerben Wierda two years ago
    The most important lessons are:
    * Statistics can be very effective and worthwhile; it’s not nonsense. But …
    * Make sure your plans for analytics do not assume you can do singulars without people in control (analytics-assisted human activity, or AHA).
    * Make sure your plans take the new brittleness of the ‘new AI’ in account (again: You will need people).
    * Make sure your new statistics-based operations are ethical.
    * Make sure you plan for much more storage and compute power close to that storage.
    * Ignore everyone who talks about “cognitive computing” or “the singularity”, and in general everyone who champions new technologies without understanding their limitations. These people are peddling General Problem Solvers, and they’re going to be very expensive to listen to.
    –end quote–

    And you all are surprised ?

    The only surprising thing for me is Mr Derek unbiased systematic failures at reporting medical and scientific topics.

    Maybe this is a Translational journal, but it is not about reporting on Medicine nor Science. It is about reporting engineering fads and being an influencer.

    Pathetic and a waste of precious time.

  81. Marko says:

    D.L : “…There was significant evidence of harm. Here’s how it works: when something is real, you continue to see a real signal as you collect more and better data. When something is not real, it disappears. Tell me again why anyone should be advocating such treatments.But your reasons had better stand up to 14,888 patients versus 81,144 comparators. Make it good.”

    Significant evidence of harm ? Here’s how it works: when something is real, you continue to see a real signal as you collect more and better data. When something is not real, it disappears. Tell me again why anyone should be advocating AGAINST such treatments. But your reasons need to be better than some bogus study of 14,888 patients versus 81,144 comparators , by a bunch of nobodies , that would never stand up to open scrutiny of the data ( which will never be allowed ). Make it good , next time.

    “A Study Out of Thin Air”

  82. Tom B says:

    It’s just a reflection of the upside-down, corrupt and politically inflamed state of science that Didier Roault, who has actually been a real scientist studying infectious diseases around the world for 40 years, is dismissed as some kind of crank, while a “study” as obviously fake as the Lancet/Surgisphere piece is lauded by all kinds of reputable people, (many of whom take a paycheck from Gilead, but not all) and instantly cited as the basis for public policy by Fauci and WHO.

    How could these Harvard profs and this prestigious medical journal have been so completely snookered? Has the Lancet ever vomited this badly in its 197 year history?

    A completely unknown doctor is reportedly named in 3 malpractice lawsuits in 2019 ( and subsequently leaves his job at a suburban Chicago hospital in February. By April he and a 5 employee company claim to have a database of patients from 600 hospitals on 6 continents? Was this man incredibly persuasive or were the Harvard docs so blinded by their desire to bury HCQ that they couldn’t resist?

    The right-wing clowns who have blindly promoted chloroquine never could have pulled this off. Fox News has been a river of lies for 25 years but I’m not sure it has ever done anything as audacious as this.

    I continue to be disappointed at the state of science and the character of scientists. You’d think with 100k people in coffins, people would stop thinking of the chloroquine question as some kind of sporting contest to be won.

  83. john says:

    From their website, Surgisphere’s nominal address is the Hancock building, on the 31st floor.

    875 N Michigan Ave
    31st Floor
    Chicago, IL 60611

    Among the options to rent space here are:
    • Office Space: Private, fully furnished and equipped offices for one person or an entire company which are customised for your needs. Options include Executive Office Suites in prestigious locations with iconic views, Disaster Recovery Spaces and Day Offices – access as and when you need it.
    • Coworking: The sociable way to work in a shared office or open plan area. Reserve a space to use every day or simply turn up and hot desk.

    I’m not sure, but I think one option available is to sort of have a prestigious address, and a timeshare sort of ‘office as you need it’.

    Not that there’s anything wrong with that. But I would expect a company doing such advanced data collection and analysis would have need for a 7 day a week office space for their employees.

    1. EugeneL says:

      “I never thought I’d tweet this…but yes it does appear the “Director of Sales” for Surgisphere is an adult model for hire.”
      Temp office, part time director part time model. What else?

      1. Robert Clark says:

        I don’t know that to be true. But the big pharmaceutical companies have been known to hire attractive young women to visit personally doctors offices to promote the doctor’s into prescribing their medications.

        One can imagine that’s the approach Surgisphere took as well to get hospitals to adopt their software.

        Robert Clark

        1. EugeneL says:

          > pharmaceutical companies have been known to hire attractive young women to visit personally doctors offices
          As directors?

          1. Anonymous says:

            Title inflation.

          2. loupgarous says:

            As “detail reps”, but I’ve seen successful (and succulent) young women in pharmaceutical marketing perform some administrative tasks in their sales territories, so it’s not implausible one might be “director of sales” in a given sales territory. Especially if she’s able to get prescribers thinking with their little heads reliably.

  84. JP Leonard says:

    Between troll and droll,
    There is a line,
    Sometimes wide,
    Sometimes fine.
    Never mind, let’s roll.

    1. NICK says:

      Thumbs up

  85. SALEH says:

    I am not advocating HCQ or any other treatement, but what I observe :
    The developped countries are nor the only place on this planet that have the corona pandemic. India decided to use the chloroquine profilaxis to all thei public servants , policemen etc.
    We in the developped countries are fixed (obnibilated) on trials dont give these facts any sort of importance.
    Many countries in the third word uses HCQ in early stages of the desease and seems to minimise the consequences of the pandemic .
    I dont think that they would continue if safety issue , or mabe they are just ireisponsible not caring about their population
    Until now HCQ seems to be OK for outpatients in profilaxis or in very early stages under strict monitoring to minimise accidents (HCQ is not a cady)
    It seems clear now that HCQ should be avoided in hospitalized patients with Myocarditis and or or with QTC issues
    Here in France some hospitals uses HCQ as a frontline first step treatement and uses monoclonal therapy (or other) as the second step for more serious conditions
    Then medications can be non exclusive and complementary
    As for ethics of trials, the odds of dying from the desease is greater with age and comorbidities.
    Older or more vulnerable persons patients have to be (always) given a real choice between accepting an RCT trial or a treatement based on best available knowledge (they can cancontribute retrospectively to reviews) I would add , even if we have no candidates for the EBM machinery.
    Propose a treatement based on the presumption of efficacy is by far more ethical than sending detected peaple back home asking them to call the emergency in case.
    Its not the first time in history when, in the name of science, the inacceptable became acceptable.

  86. PB says:

    Is there any possible explanation for so many to have accepted and even touted this bogus Lancet study other than idiot level gullibility or ideological possession that disables the capacity for critical thinking? Just wondering.

    1. EugeneL says:

      It did not look bogus initially. It’s a good that some members of the public looked at the claims and the date more critically.

  87. john says:

    Relative stats for NY, Montreal, Paris, and Marseille

    See also:

    But if you google Didier Raoult, this is the 3rd link that Google Search will show you:

    This is for those who still naively think that Covid-19 science has not become politicized. To show how a respected scientist who has published more than 2900 papers, is being attacked because he dared to publish his case series results using HCQ and AZT.

    On twitter, there is a mini tsunami of epidemiologists and big data researchers calling into question the honesty of Mehra’s study, and if it really ever was a study. You’ve been hosting an excellent blog on the subject. You were fooled, I was fooled. Now, to correct this, and to maintain your own excellent credibility, I think opening up a new blog chapter or topic focusing on the validity issues of both Mehra’s NEJM paper and Lancet paper would be in order.

  88. john says:

    Or, maybe not necessary. In this day and litiginous age, one has to be most careful about being accused of libel,etc. It appears that the truth or falsity of the Lancet (and possibly also, the NEJM) studies will be coming out shortly.

  89. JP Leonard says:

    After more than 100 scientists sent an open letter questioning the Lancet study, the Lancet made some minor corrections but left findings unchanged and 9 of the 10 objections unanswered,

  90. john says:

    Interesting graphic from France-Soir reproduced here:

    It basically, shows that mortality in the Marseille region due to Covid-19 is much lower than in many other areas.

    What I find fascinating is, the attacks of Prof. Raoult by various segments of the press (e.g. NY Times article focusing on personality) and this blog, which magically and consistently pops up #2 whenever you Google Didier Raoult:

    It’s amazing the extent of the targeted character assasination of a most reputable scientist that is going on.

    So, if you are waiting for “Expressions of concern” and/or retractions from NEJM or Lancet re the Mandeep Mehra papers, perhaps you shouldn’t hold your breath.

  91. john says:

    I haven’t been much of a twitter fan and so haven’t realized how revealing twitter can be.

    I looked at the twitter feed of Richard Horton, the chief editor of Lancet.

    I was amazed as to how political and polarizing this person was. I don’t think that medical or other scientific journals should allow persons who are so deeply immersed and engaged in political agendas, to be their editors. I believe that the role of advocate and scientist, if not incompatible, must be clearly compartmentalized.

    I now am convinced that the Mehra paper will probably not be withdrawn any time soon, barring some sort of legal action requiring full disclosure of the data use in their study.

    1. EugeneL says:

      Sadly, I agree. The article is not going to be retracted, even though it was clearly based on a dodgy data. Too much politics is involved, and money. Those hundred scientists who want to audit the method and data should shut up and trust Surgisphere. It has pay for hire models among directors after all. Derek, will unlikely issue any clarifications either. His hate to Trump likely exceeds the love for honest and open scientific process. It’s good that the at least has not descended to silencing commenters based on their political point of view.

      1. Derek Lowe says:

        Sorry to disappoint you, but I will be writing about this today.

  92. SALEH says:

    Cumulative worldwide healthcare authorities in many countries advocate for the early and large use of HCQ and are intending to co continue with it.
    They represent hundred of thousand of treated persons (curatively or profilaxis)
    Are they foolish ??
    What is happening now is that they dont understand the positioning of the WHO
    Concerning the EBM and RCT , Time is running and death toll is climbing , believe me , I have been reading hundreds for other subjects , it will be doubtfull to expect franc non contradicting results that might lead to endless discussions and might appear useless for decision making.
    All in all, RCTs is heavy duty and have usually low external validity . Compared to prevalent shared opinion by so many health authorities in the world I would rather take in such a crisis the second one.
    If RCT don’t confirm the large shared opinion about a cure , this have to do maybe with the RCT methodology rather than the large shared opinion.
    It would be wise, to stop a second, and have a broader look at the picture rather than loose time debating on details.
    Remember most scientific discoveries happened before EBM era. They are the fruit of intuition and curiosity.
    Still, I don’t deny that scientifical méthodology is central in modern research but in a more calm situation.
    If presumption of efficacy of a treatment is the only available knowledge to date, this has to benefit to the patient (the benefit of doubt).

  93. SALEH says:

    I’ll add this to my precedent comment , HCQ is given as an example to underline the éthical dilema surounding the COVID pandemic.
    Many different therapeutical approches are now tested in trials around the globe (not only HCQ).
    Again persons above 70 specially with comorbidities have around x10 times the risk of developping a seroius condition and even fastly dying from it.
    Including them in RCT is not ethical. Applyed to the the most vulnérable patients , the standard treatement branch of RCT (placebo) is not acceptable with regard to the risk level. (patients might accept an RCT as the only way to have a chance to get the treatement groupe).
    They have to be targeted and helped and be given the best available treatement (not the standard one) built on cumulative knowledge from undergoing trials (whatever the product is)

  94. DTX says:

    john – Thanks much for posting the Richard Horton twitter feed! While I obviously knew about the Lancet, I had never paid attention to its editor. It was shocking to see he recently called for Anthony Fauci to resign. I guess Horton thinks politics are more important than health.

    In terms of scientific voices in the US regarding the pandemic, is there anyone more important than Fauci? And he should resign? This suggests to me that data quality on HCQ is likely irrelevant to Horton – that his judgments focus on politics & not science.

    Hence, while I’m glad john posted the twitter feed, it’s really disturbing to see such a (formerly) highly respected journal devolve.

    1. Suggesting that Fauci resign does not demonstrate that the suggester has been carried away by political bias. Someone who believes in the mission of an organization might resign if he or she decided that the organization had lost track of that mission, and that he or she might better serve that mission elsewhere. In the case of a prominent person like Fauci, he might decide that his resignation would contribute toward jolting the organization into getting back on track.

      I do not say that Fauci should resign, but only that he might do so for reasons independent of his politics.

  95. john says:

    NEJM publishes “Expression of Concern”

    Direct link here:

    “On May 1, 2020, we published “Cardiovascular Disease, Drug Therapy, and Mortality in Covid-19,”1 a study of the effect of preexisting treatment with angiotensin-converting enzyme (ACE) inhibitors and angiotensin-receptor blockers (ARBs) on Covid-19. This retrospective study used data drawn from an international database that included electronic health records from 169 hospitals on three continents. Recently, substantive concerns have been raised about the quality of the information in that database. We have asked the authors to provide evidence that the data are reliable. In the interim and for the benefit of our readers, we are publishing this Expression of Concern about the reliability of their conclusions.

    Studies of ACE inhibitors and ARBs in Covid-19 can play an important role in patient care. We encourage readers to consult two other studies we published on May 1, 2020, that used independent data to reach their conclusions.2,3”

    Lancet looking less reliable by the day.

  96. Edward R says:

    I couldn’t help but notice that the Bahrain MoH has been using the hydroxycholoquine protocol since February 26th of 2020.

    I can only wonder if that’s why the Worldometer Coronavirus stats today show Bahrain at :

    12,311 cases, 7,407 recoveries, and only 19 deaths.

    Seems there are a lot of HCQ protocol countries on that list with low deaths.

    1. JP Leonard says:

      Madagascar, home of the wormwood tea cure (artemisin annua), is showing a total of just 6 deaths on Worldometer. It’s also used in Chinese medicine.
      It’s normally used against Malaria but people are drinking loads of bottles of the tea there now for Covid 19.
      googling on it led to salinomycin, also against malaria – known to kill plasmodium fast and also used to target cancer cells, nothing comes up on salinomycin vs. covid19

    2. Sabbir Rahman says:

      Given the obvious problems with this study, it is hard to see how it passed peer review unless the journal itself was complicit, together with the lead author, in promoting the conclusion that HCQ is harmful. The fact that a competent body such as the WHO would immediately publicise the results so widely despite its obvious flaws also strongly suggests complicity.

      Of all the drugs undergoing trials it would be strange that there would be such a concerted effort to prevent HCQ from being investigated properly unless it was somehow considered a threat. That could only be the case if (i) it genuinely constituted a significant danger to the public – which seems highly unlikely as it is a well-known drug that has been administered safely for decades, or (ii) if HCQ is actually likely to be efficacious – and indeed a number of smaller scales studies have shown this to be the case when it is administered in combination with zinc supplements in an appropriate way.

      Now, the second of these two possibililties would clearly be to the considerable benefit of the general public in terms of saving lives, and the only reason that it could possibly be considered a threat by the parties concerned is if they were acting on behalf of entities who would be affected negatively should drugs such as HCQ be found to be effective and come into widespread use.

      It is fairly clear that the only parties that would be negatively effected by widespread use of HCQ as an effective treatment for COVID-19 would be the profit-driven pharmaceutical companies, organisations and high-net-worth individuals who stand to gain significantly from sale of newer drugs or vaccines which are still under patent. Effective treatments for COVID-19 through repurposing of low cost generics would pose a considerable financial threat to this promising source of income.

      The lead author of the article, Professor Mandeep Mehra, whose research is funded by pharmaceutical companies, certainly does not shy away from making his bias against the use of HCQ clear on his LinkedIn page, or that Bill Gates is one of his key influencers. In addition, besides contributions from individual goverments (no longer the US), the WHO receives its greatest funding contributions from the two largest pro-vaccine organisations, namely the Bill & Melinda Gates Foundation (which is now its largest single source of funding) and the GAVI Alliance – whose founding partners include the Bill & Melinda Gates Foundation, UNICEF, the WHO itself and the World Bank, and whose broader alliance includes the pharmaceutical industry.

      It does not require a great deal of analytical thought to recognise the corruption that must be going on here. The pharmaceutical industry and the vaccine lobby appear to have leading academics, top journals and even global health organisations in their back pockets, and corporate and individual greed is being given priority over the preservation of human life.

      1. drsnowboard says:

        Oh look , the old hop skip and conspiracy jump to evil pharma and Bill Gates having secret HCQ suppressing discussions. I would ask for evidence but you’ll trot out some epochtimes video or a screenshot of a patent from the SARs days. Perhaps best to go shout in your other echo chambers?

        1. Sabbir Rahman says:

          How about this one from a few days ago:

          May 24, 2020: Philippe Douste-Blazy, Cardiology MD, Former France Health Minister and 2017 candidate for Director at WHO, former Under-Secretary-General of the United Nations, reveals that in a recent 2020 Chattam House closed door meeting, both the editors of the Lancet and the New England Journal of Medicine stated their concerns about the criminal pressures of BigPharma on their publications. Things are so bad that it is not science any longer.

  97. Shawn Sague says:

    Statement from The Lancet

    Today, three of the authors of the paper, “Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis”, have retracted their study. They were unable to complete an independent audit of the data underpinning their analysis. As a result, they have concluded that they “can no longer vouch for the veracity of the primary data sources.” The Lancet takes issues of scientific integrity extremely seriously, and there are many outstanding questions about Surgisphere and the data that were allegedly included in this study. Following guidelines from the Committee on Publication Ethics (COPE) and International Committee of Medical Journal Editors (ICMJE), institutional reviews of Surgisphere’s research collaborations are urgently needed.

    The retraction notice is published today, June 4, 2020. The article will be updated to reflect this retraction shortly.

    1. NICK says:

      Great news! “When the false falls away on the truth remain.” = Science.

      1. NICK says:

        Sorry . ‘When the false falls away only the truth remains.”

        1. Sabbir Rahman says:

          [I posted this elsewhere but will copy here FYI]

          Now that we have some more information, a significant clue as to what may be going on is the failure by Professor Mehra and the Lancet to disclose a clear conflict of interest, namely that Gilead Sciences currently has two ongoing trials of its COVID-19 drug Remdesivir being carried out at Brigham & Women’s Hospital, of which Mehra is a Director:

          Hydroxychloroquine is of course in direct competition with Remdesivir as a treatment for COVID-19 so this failure to disclose should immediately start ringing alarm bells. It clearly begs the question as to whether Gilead may have had any involvement in the preparation of the retracted Lancet article or had perhaps instigated it.

          The other missing piece of the puzzle relates to the source of the raw data. Given that Surgisphere seems to have had insufficient resources to fabricate such a large dataset without additional help, it would be worthwhile looking into whether perhaps a pharmaceutical company – again Gilead being the natural first candidate given the circumstances – could have been the actual source of the data.

  98. Sabbir Rahman says:

    I do not think that the various parties involved with study should be allowed to simply make their apologies and quietly disappear into the background. Many lives are at stake here, and a in-depth investigation is called for in order to establish what really happened.

    Like most of us, I do not know how effective HCQ is when used in various combinations and contexts. However, it is perhaps possible that many of us are unaware of quite how large a number of people around the world have been taking, and indeed continue to take HCQ despite the WHO’s warnings against its use. If it were not showing considerable efficacy, I seriously doubt that so many countries would have insisted on continuing to use it.

    For example, Prof Mehra on his LinkedIn page “likes” the comment by his Harvard Medical School colleague Haider Warriach praising the article Mehra et al just published in JAMA by his entitled “Prescription Fill Patterns for Commonly Used Drugs During the COVID-19 Pandemic in the United States” where they show that there were a staggering 483,425 excess fills of HCQ prescriptions during the 10-week period from 16 February to 25 April 2020 as compared with the previous year. Note that Mehra also “likes” Daniel Goldstein’s comment that “WHO halting enrollment of patients into the HCQ/CQ arm of the large SOLIDARITY trial based on potential harm data published on 5/22/20 in Lancet by Mandeep Mehra, MD FRCP et al.”, so it is clear that he was rather pleased with this outcome of his paper, and it is fairly safe to assume that he is not pleased by the very large number of people currently taking HCQ, which is why he was so keen to highlight this fact in his JAMA paper:

    And that is just in the US. In India, “all healthcare workers in hospitals and some frontline staff” dealing with COVID-19 continue to be administered with HCQ, despite WHO’s advice, because they are seeing “no harm” and potential benefits from its use as a prophylactic:

    In Brazil, which currently has the highest growth rate in COVID-19 cases worldwide, they are also continuing to recommend HCQ as the default treatment in defiance of the WHO, though the matter has now become highly politicised there:

    Turkey “has made significant progress in treating coronavirus patients in the early stages of the disease with the controversial malaria drug hydroxychloroquine”, with the proportion of coronoavirus cases registered with pneumonia dropping from 60% on 24th March to 19.5% on 6th April. Needless to say, Turkey has also insisted on continuing the use of HCQ despite the WHO’s concerns:

    In South Korea, HCQ has been one of the preferred treatments according to physician guidlines since at least February. In a retrospective study by Samsung Medical Centran and PNU of the use of HCQ as a prophylactic, of 184 patients and 21 care workers who had been exposed to COVID-19 at a long-term care hospital where massive COVID-19 infections were reported, 100% of those treated tested negative for the virus after a 14-day quarantine period. Amusingly, they were not able to prove that HCQ is effective for the prevention of COVID-19,” as there was no adequate control group:

    In Algeria, Dr. Mohamed Bekkat, a member of the Scientific Committee monitoring the evolution of the COVID-19 pandemic, said that,, “We have treated thousands of cases with this drug with great success to date. And we have not noted any adverse reactions”, and “We have not recorded any deaths related to the use of (hydroxy)chloroquine”. Algeria is continuing to use HCQ despite the WHO’s decision to suspend clinical trials:

    It is the same story in Morocco:–20200528-0008.html

    Honduras has also been using HCQ as their default treatment for COVID-19. According to an article appearing on 5th May, the Honduran health minister ‘insists that patients who were treated with hydroxychloroquine in four different hospitals have responded satisfactorily, and that doctors have been using this treatment plan for over a month now’, and has stated that, “Hydroxychloroquine is used to treat malaria and will not cause harm to anyone, because doctors take extra care when treating patients with heart problems”:

    El Salvador had also been using HCQ as the default treatment until the WHO recommendation against it was announced. Rather interestingly, El Salvador’s Bukele questions why world leaders are being told to take HCQ [by who, exactly?] while the public is being warned away from it:

    Russia continues to stand by use of HCQ, and according to the Health Ministry, “domestic experience indicates the validity of the use of hydroxychloroquine when it is prescribed in certain groups of patients with COVID-19 in low doses”:

    Although some countries such as Italy, Belgium, France, Portugal, Egypt Tunisia, Colombia, Chile, Cape Verde, Albania and Bosnia have suspended use of HCQ on the basis of the WHO’s recommendations based upon the dubious Lancet study, many other countries that have had positive experiences with HCQ have retained it on their the list of approved drugs for the treatment of COVID-19 or for clinical trials despite the WHO’s recommendations against it:

    Are you starting to see a pattern here or shall I go on? I had started making a list of other countries continuing to treat patients with HCQ, but it quickly became apparent that the list was going to be a rather long one.

    Just as an indication of the extent to which HCQ is being tested or applied, India, which is world’s the largest manufacturer of HCQ and many other generic drugs, has exported large amounts of HCQ to at least 55 other countries, including the US, Mauritius, Seychelles, Afghanistan, Bhutan, Bangladesh Nepal, Maldives, Sri Lanka, Myanmar, Zambia, Dominican Republic, Madagascar, Uganda, Burkina Faso, Niger, Mali Congo, Egypt, Armenia, Kazakhstan, Ecuador, Jamaica, Syria, Ukraine, Chad, Zimbabwe, France, Jordan, Kenya, Netherlands, Nigeria, Oman, Peru, Philippines, Russia, Slovenia, South Africa, Sri Lanka, Tanzania, the United Arab Emirates, Uzbekistan, Urugway, Columbia, Algeria Bahamas, Mauritius and the United Kingdom:

    Perhaps all of the above evidence is merely “anecdotal”, but I think at some point one needs to draw the line and apply just a little common sense, and acknowledge that, despite the lack of clinical trials to prove it formally, HCQ has been showing considerable efficacy on the ground for some time in many countries worldwide, and as a consequence of these positive experiences, continues to be administered.

    If the above information can be scraped from the internet by an amateur sleuth in a matter of a few hours, then it is stands to reason that the WHO will have a far more comprehensive understanding of the extent to which HCQ is being used worldwide and its efficacy. It is therefore not feasible that the WHO could be unaware that the outcomes of the Lancet study quite blatantly contradict the results being reported to them by the many countries worldwide actively administering HCQ, and therefore also rather hard to come up with a rational ethical justification for their blind acceptance of the conclusions of that study leading to their recommendation that clinical trials of HCQ be stopped.

    The matter seems so clear that even the inevitable defense of simultaneous “incompetence” on the part of both the Lancet and the WHO cannot satisfactory explain their troubling behaviour, and given that so many lives are at stake, a detailed investigation in to what really happened is certainly warranted.

  99. m00 says:

    It’s a widely known fact that since losing the British-American war UK hates America and therefore Trump, so they obviously bias-rigged the trial to make him look bad. Beating Covid is definitely not as important for science as making a foreign inept leader look more inept … Also, Zinc!

    1. Some idiot says:

      Brings to mind a line from the late, missed Dave Allen: “People ask me why I don’t make jokes of politicians. The reason is that they do too good a job themselves…”

  100. SALEH says:

    The main question of this RCT is what was the delay between onset of symptoms and the HCQ.

    1. Sabbir Rahman says:

      Yes, I think that is right. The negative results of the study really have absolutely nothing to do with Donald Trump and everything to do with how hydroxychloroquine is administered in the UK.

      In the UK, NHS doctors are not allowed to prescribe HCQ for COVID-19. In the hospital setting, my understanding is that HCQ is typically only administered when the disease has become severe and other medications/interventions have failed.

      Of course HCQ is no longer efficacious when administered at such a late stage and instead becomes toxic. This would explain the poor outcomes reported here.

      I don’t think that there is anything more to it than this. However the headline conclusion that “hydroxychloroquine ‘does not save lives” is incorrect, as the evidence available globally is that it does when taken early on and in an appropriate combination with other drugs such as azithromycin and/or zinc sulphate.

  101. CJ says:

    To be fair, why not also share the evidence that shows HCQ is beneficial?

    Allow the doctor and patient to assess to all evidence and decide what’s best. I don’t understand sharing only one side of the story. Does withholding information save lives?

    Someone’s life could be saved. Just ask Amy Klobachar about her husband:


    1. Sabbir Rahman says:

      There was a nice paper published just a few days ago in the American Journal of Epidemiology by Professor Harvey Risch at Yale that you might find of interest:

      “Hydroxychloroquine+azithromycin has been used as standard-of-care in more than 300,000 older adults with multicomorbidities, with estimated proportion diagnosed with cardiac arrhythmias attributable to the medications 47/100,000 users, of which estimated mortality is <20%, 9/100,000 users, compared to the 10,000 Americans now dying each week. These medications need to be widely available and promoted immediately for physicians to prescribe."

      1. JL in Jersey says:

        This seems pretty straight forward early intervention with chloroquine makes a positive difference. Staying out the hospital and the ICU are to my mind game changers. The comments for this blog are amazingly worthwhile and interesting.

        I was once a frequent traveler to central Africa and was prescribed the drug. In Africa I saw advertisements for its use on infants. So I was surprised by all the recent warnings.

        1. Barry says:

          If hydroxychloroquine (or chloroquine) were effective early interventions, people already on them (for lupus…) would be under-represented in hospitalizations, and in deaths. That experiment was handed to us by nature. Hydroxychloroquine failed.

          1. Najibj says:


  102. SALEH says:

    Agree with SABBIR RAHMAN. We maybe look, in the developed countries, at these facts as this with some disdain.
    According to RAOULT : 4 milliard people are living in countries that authorised the use of HCQ
    RCT already are already here, yielding contradictory results about HCQ , some shows improvement some shows no improvement.
    EBM will have difficulty answering clearly the question
    I don’t have any definitive opinion on efficacy of HCQ, but Health authorities is those countries have a good opinion on HCQ and are not ready to give up.
    I think that HCQ prescription have to be available everywhere with the condition of real security monitoring specially arrhythmia and QTC. This apply to other medical approaches that shows some benefits on the base of simple observational trials.
    In France we say “ Le doute doit bénéficier au patient” : In case of doubt , this has to benefit to patient.
    Relying on the presumption of efficacy (HCQ or other products) is by far, more ethical than include vulnerable persons on RCT with the knife on the neck.
    All in all , RCT should not be proposed to vulnerable or very vulnerable persons combining vulnerability with late entry after onset to a hospital with regard to the known high mortality rate here.

  103. Stack Pointe says:

    It is likely that one day, someone will estimate the number of deaths caused by refusal to use a treatment that President Trump happened to mention as “promising.”

    I’m guessing 50,000 in the US.

    1. RA says:

      Nope. Much of the preventable death is on Trump:

      Trump waited too long to shut down travel from Europe, which seeded most of the US outbreak…less political pizzaz to shutting down travel from the supremely white countries, you know? So while Trump was rattling sabers at China, COVID poured into the country from Europe. Oops.

      Trump discouraged the use of masks…one of the biggest public health blunders ever..universal masking would have done more than any drug.

      Trump downplayed the threat and never initiated a national lockdown..piecemeal state by state approach..had the country locked down 1 week earlier there would have been 36K lives saved.

      Trump discouraged testing so to make the numbers look better….oh, by the way…even if hydroxychloroquine worked early in the disease, many people wouldn’t benefit because they couldn’t get a timely test thanks to Trump not ramping up testing nearly enough.

      Because of Trump’s sustained effort to gut the Affordable Care Act, more people are uninsured and thus couldn’t get care until forced to go to the hospital. If the courts listened to his “promising” idea to overturn the ACA, that would be millions more unable to access any care…like a doctor to prescribe your precious hydroxychloroquine.

      If you think Hydroxychloroquine could have saved 50K lives, then the deaths are the result of Trump refusing to get a legitimate early-stage trial of Zelenko’s system done by now. Oh, Fauci and the deep state stopped him, right? Oh, please. If Trump were motivated, he’d put as much effort into getting a real early-stage clinical trial as he did in trying to get a Ukrainian Biden investigation. If Dr. Trump really wanted to promote HCQ, he would have raised hell, threatened to withhold the NIH’s funding unless they studied the Zelenko system exactly…but he didn’t do that. So, either he doesn’t believe his own BS to use the levers of government to make it happen or he is weak and incompetant…which is it?

      Trump let the virus ravage urban blue America. Perhaps he wasn’t kidding when he recently re-tweeted a video saying “the only good Democrat is a dead Democrat.” Clearly, the playbook going forward is to spread the BS that if only we had listened to Trump all the death (he caused) would be avoided. Spare us the crocodile tears over the dead, please!

  104. SALEH says:

    Upon a recent méta-analyse from Raoult , most observational trials and some RCT are in favor of HCQ versus none from big data
    Again most countries in the under developped countries have been using HCQ and seemed satisfied in terme of efficacy and tolerance.
    Some RCT are still going on here and there hoping that they will yield something (either way )
    As I said before , it is doubtfull to get a clear non contradicting results
    Wait and see

  105. SALEH says:

    Etude Pirnay (Pirnay trial)
    Very nteresting new observational French trial under HCQ AZITHRO of old and very old persons living in nursing home (the first of its kind).
    The trial includes 68 residents with a medium age of 86 years, early treated with HCQ –Azithro within 2.5 days of onset of symptoms (Raoult protocol)
    Cardiac tolerance : 2 QTC prolongation (treatement stopped)
    Only 7 (10.3%) died within the experimental periode (same as median death for the same periode in 2019, 2018) compared to 20-30% median « above everage » death in old peaple homes in France. The delta here is then around is 10 versus 30-40%.
    Even if it is not an RCT, still this delta is amasing
    It is the first trial of its kind includin

  106. brian says:

    Treatment with Hydroxychloroquine Cut Death Rate Significantly in COVID-19 Patients, Henry Ford Health System Study Shows

    In a large-scale retrospective analysis of 2,541 patients hospitalized between March 10 and May 2, 2020 across the system’s six hospitals, the study found 13% of those treated with hydroxychloroquine alone died compared to 26.4% not treated with hydroxychloroquine. None of the patients had documented serious heart abnormalities; however, patients were monitored for a heart condition routinely pointed to as a reason to avoid the drug as a treatment for COVID-19.

    1. Derek Lowe says:

      Keep in mind the age distributions in the different cohorts and their likelihood of simultaneous steroid treatment.

      1. NICK says:

        And the keep in mind they didn’t start as early as possible and still no zinc.

      2. NICK says:

        Imagine if they really designed a study to start HCQ at the proper dose ( no the crazy high doses uses in other studies) as early as possible and measure zinc levels and supplement with zinc and and arm with or without Azithromycin. We would have even better outcomes.

        1. ghost of q.mensch says:

          @ Nick: perhaps you would be interested in this comment #54 by Island girl on Chris Martenson’s peak prosperity blog : “Where’s the zinc [?]”

          Multi million $ Gain of Function grant awardee virologist researcher Ralph S. Barac published way back in 2010 that Zn+2/ionophores (ie HCQ, CQ, quercetin, flavinoids etc) inhibited CV replicase activities in cell culture and in vitro, but never thought to mention it, in the interests of public health, once the pandemic hit, and the HCQ/Zn politicized science scrum raged over the last few months.

          “After re-reading the Henry Ford Hospital Study this morning and noting no zinc was used, I started a literature search on Zinc and ionophores. This paper caught my eye. Back in 2010, Ralph S. Baric and other coronavirus researchers studied the potential for Zn and ionophores to block viral replication in vitro and in cell culture. That’s 10 years ago

          What first suprised me was how old these data are. We’ve known this for a long time. But then what caught my eye and startled me was the author list. Ralph Baric.

          In 2015, Ralph S. Baric and his protege, Shi Zheng Li from Wuhan Institute of Virology, among others, published their creation of a chimeric SARS virus with S protein adapted for greater infectivity and morbidity – part of the gain of function research program:

 ” [ …]

          1. NICK says:

            Great info! Thank you

          2. Trew says:

            The fundamental problem with adding zinc ionophores to the body resides in excess Zn(II)’s toxicity to the cell and induction of apoptosis. Free Zn(II) is promiscuous in the cell and binds to and/or inhibits a great many targets. This is why free zinc levels are so low. Finally, I do not believe HCQ was used in the 2010 paper you cited but was used in a 2014 paper which also shows a high degree of activation of apoptotic associates proteins..

    2. matt says:

      Keep in mind the Henry Ford study found a significant mortality risk to being white (yeah, yeah, queue up all the bad Detroit jokes), but to my knowledge any effect like this would be extremely weak–even in the Michigan state demographics, the percentage of white deaths is similar to the percentage of white diagnosed cases. This is also true in several other states I’ve looked at, although the number of “unknown race” people might hide a smallish effect.

      As noted by many others, the Henry Ford study found no benefit to steroid or tocilizumab, whereas more powerful and trustworthy prospective RCTs have indicated those are significantly beneficial.

      Also, the Henry Ford study “no-treatment” cohort were more likely to die, but less likely to be in the ICU and less likely to be put on a ventilator. That’s a little non-intuitive, don’t you think, if they were more sick because they weren’t getting this life-saving drug?

      I don’t know why the Henry Ford study had these oddities–that’s the trouble with retrospective studies, they can be fooled more easily by unmeasured, uncontrolled systematic biases (not necessarily human bias, mind you, but factors that skew the results and you may not have known to control for them). If you look at Figure 2, the number of patients at risk (and the number of patients still hospitalized), is much lower at every time point for the no-treatment cohort. Deaths alone cannot account for that, there must have been more drop-outs in the no-treatment cohort? But they claimed to have few drop-outs. I don’t know how to reconcile those numbers.

  107. SALEH says:

    The recent NY Mount Sinai 8 hospitals large retrospective cohort seems to indicate a clear HCQ effect (the clearest HR among all the risk factors they studied) . It seems more and more hard to beleive that cumulative and concording results from many retrospective huge cohort are just the fruite of miscalculations.

  108. SALEH says:

    NY Mount Sinai 8 hospitals large retrospective cohort seems to indicate a clear HCQ effect (the clearest HR among all the risk factors they studied) . It seems more and more hard to beleive that cumulative and concording results from many retrospective sometime huge cohort are just the fruite of miscalculations.

  109. ghost of q.mensch says:

    Here is a recent July 8 quite comprehensive review of the highly politicized saga of HCQ in Covid19. Touches upon the fake data/fake science of the retracted Surgisphere-Lancet paper, the dosage screw-ups (“I thought HCQ was the antiamoebic dysentery 8-OH-quinoline drug class) of the Oxford-Martin Landray RECOVERY trial, and the NIAID-VA “Mostly Blacks At death’s door” study.

  110. NICK says:

    Conclusions: Risk stratification-based treatment of COVID-19 outpatients as early as possible after symptom onset with the used triple therapy, including the combination of zinc with low dose hydroxychloroquine, was associated with significantly less hospitalizations and 5 times less all-cause deaths.

    1. Barry says:

      Not only won’t hydroxychloroquine cure your Covid19; it could kill you
      cardiac toxicity of hydroxychloroquine in COVID-19
      Christian Funck-Brentano
      Lee S Nguyen
      Joe-Elie Salem
      Published:July 09, 2020DOI:

      1. NICK says:

        Chloroquine, but not hydroxychlorquine, prolongs the QT interval in a primary care population

        Conclusions: In subjects free of COVID-19, we found a small increase in QTc associated with use of chloroquine, but not hydroxychloroquine. We found no increased mortality associated with use of hydroxychloroquine.

      2. NICK says:

        You can reduce the chance of QT prolongation buy take OTC potassium supplement.

        Normalization of Acquired QT Prolongation in Humans by Intravenous Potassium

    1. David E. Young, MD says:

      Well, the Henry Ford study was bogus. The people who got HCQ fared better, but was it due to the HCQ? It might have been due to the high dose steroids that they also received. Remember, extraordinary claims require extraordinary proof. The Henry Ford retrospective study was hardly any proof at all. And Zev Zevenko? I’d like to see his office notes, because 2,200 patients in 4 months? Look, if you see the patient 4 times (one to first see them, a second time to go over the results of the tests and explain their treatment, a third office visit to make sure they were getting better and a fourth to make sure they had returned to normal health), then 2,200 patient makes….. goodness….8,800 visits. Over 18 weeks that’s about 480 visits a week or almost 100 office visits a day. You really think that he is capable of that? Never stopped to think about that, did you? And the other 4 studies? Well, there was no reference to them and I sure have not heard about them. Are they as bad as the other studies?

  111. NICK says:

    It could be concluded that spectrum of COVID-19 mostly affects young adult age group (third to fifth decades of life), a finding that contrasts with documentations from other countries. The percentage of male gender to be afflicted with COVID-19 was more. Majority of patients (nearly three-fourth) of COVID-19 disease were asymptomatic at the time of diagnosis and presentation. Symptomatic presentation was more common in old age population. Infectivity was higher in patients who had underlying co morbid diseases especially with multiple co morbid diseases. The average recovery time from COVID-19 was 8 days with effective treatment. Mortality in COVID-19 was higher in old age population, male gender, symptomatic and in patients with co-existing co morbid conditions. Most of mortality was noted within in few days of admission suggestive of early mortality due to primary disease. The recovery percentage was lowest with recovery duration being maximum in critically ill patients and the opposite trending was observed in asymptomatic patients on HCQ treatment. It was observed that putative definitive management protocol with HCQ enhances the chances of early recovery, modulating the overall mortality profile of COVID-19.


    The limitations of the study include its small sample population size with lack of complete follow-up. Ethical approval: Approval was not required.

    1. matt says:

      You can’t bundle up a hundred piles of crap studies and produce good data. It is quite possible, likely even given the poor quality of the studies you are eagerly accepting, and your bias in looking only for studies that confirm your ideas, that every one of these weak retrospective studies is giving you the wrong answer. Or, perhaps more accurately because they often tell you straight out they cannot give you an answer, you are deriving the wrong answer from the tea leaves at the bottom of your cup.

  112. JP Leonard says:

    What to make of this study?
    “COVID19 PCR Tests are Scientifically Meaningless – Though the whole world relies on RT-PCR to “diagnose” Sars-Cov-2 infection, the science is clear: they are not fit for purpose” by Torsten Engelbrecht and Konstantin Demeter
    They say that PCR is meant for replication not for diagnosis. It tests RNA, and how can we be sure this RNA comes from Covid19.
    They also seem to say that Sars Cov 2 has never been isolated. Whoa. Are the authors questioning if it even exists?

    If it doesn’t exist then what has been going on? Maybe just old sick people dying from a bad flu and worse nursing home conditions?
    I’m not sure the authors are just demolishing the testing procedure, or outright questioning the existence of the “presumed” novel virus.

    Googling on isolation purification of sars-cov-2 the top hit is “Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein” in Cell (Walls et al, 1000+ citations, )
    It mentions isolates and purification batches.
    Too bad. I kind of liked the idea of a world wide hoax. We’ve been given so much conflicting information about it that its non-existence could be the most parsimonious explanation.

    Short of that, the authors do seem to score some direct hits.

  113. Carl says:

    I’d like to get your take on this hydroxychloroquine study,, that was just done in the Henry Ford Health System and written up in the International Journal of Infectious Disease. The findings are: “Hydroxychloroquine provided a 66% hazard ratio reduction, and hydroxychloroquine + azithromycin 71% compared to neither treatment (p < 0.001)."

    1. Derek Lowe says:

      Look at the age differences between the cohorts and the likelihood that they got dexamethasone treatment.

      1. Carl says:

        Thanks for the response. I took another look at the study and, if anything, it looks like the HCQ+AZM cohort is older than the control group. Also, steroid usage is tracked, although, admittedly more of the HCQ+AZM users received steroids than did the control group and the control group was small. Nevertheless, HCQ+AZM seems to have a far greater effect on the hazard ratio than does the steroid.

  114. NICK says:

    Hydroxychloroquine could save up to 100,000 lives if used for COVID-19: Yale epidemiology professor
    One study found that early administration of hydroxychloroquine makes hospitalized patients substantially less likely to die

  115. NICK says:

    Hydroxychloroquine could save up to 100,000 lives if used for COVID-19: Yale epidemiology professor

    1. David E. Young, MD says:

      It’s called the “fallacy of authority”. You indicate that since Reich is a Yale Professor that he must be correct. Well, I don’t believe it for a minute. Even a Yale professor can fall into the trap of believing something that is not true. Do the Randomized Clinical trial and the we can talk.

  116. lisa callahan says:

    Why would anybody lie about what is helping their patients??? Why are we so hell bent on proving them wrong? Why the “Jihad” on hydroxychloroquine??? It is seriously mind boggling to me. What advantage does someone have prescribing a $12 treatment? I’d take it in a minute if I start feeling ill…while I wait for some wonky vaccine.

  117. Kenneth says:

    Thanks fro the update. This drug has the capacity to save a hundred of millions of people around the world so what do we have to lose?

  118. An Old Chemist says:

    The following website lists over 100 studies published to date on HCQ and Covid-19:

    These studies have been classified into four categories depending on the timing of the HCQ treatment:

    PrEP – used as pre-exposure prophylaxis
    PEP – used as post-exposure prophylaxis
    Early – patient treated at an early stage of Covid-19
    Late – patient treated at a late stage

    Note that all the studies that produced negative results were for the late treatment. For all other stages of treatment (PrEP, PEP, and Early), nearly all the studies show positive results for HCQ.

    If a new and patented drug (like Remdesivir) had produced so many positive studies, it would have been promoted by the US media as the greatest wonder drug of the 21st century.

    Incidentally, delayed approval of HCQ by the FDA may be costing thousands of Americans their lives.

  119. An Old Chemist says:

    The following website lists over 100 studies published to date on HCQ and Covid-19:

    These studies have been classified into four categories depending on the timing of the HCQ treatment:

    PrEP – used as pre-exposure prophylaxis
    PEP – used as post-exposure prophylaxis
    Early – patient treated at an early stage of Covid-19
    Late – patient treated at a late stage

    Note that all the studies that produced negative results were for the late treatment. For all other stages of treatment (PrEP, PEP, and Early), nearly all the studies show positive results for HCQ.

    If a new and patented drug (like Remdesivir) had produced so many positive studies, it would have been promoted by the US media as the greatest wonder drug of the 21st century.

    1. john says:

      I thought that with the Surgisphere debacle, that ivermectin was dead, but apparently not.
      If this is true, then there have been some very positive results with ivermectin using triple therapy. Here is an article describing the experience by Dr. Thomas Borody.

      By the way, Derek, your time limit on your Akismet settings is too severe. It’s almost always triggered.

  120. gusbag says:

    Here’s another RCT for early HCQ treatment, with Zinc even! Unfortunately, just like other more reputable studies it shows no real benefit for Covid :(.

    1. theasdgamer says:

      Not so early after all. Waited for test results before enrollment. After that treatment was shipped. 70-140 hours post symptom onset.

      Not so early after all.

  121. Gerry says:

    Amazing how much has happened since this article was posted. The main thing being that the Lancet has to retract the article regarding HCQ not working and having serious side effects. Turns out the company doing the research “Surgisphere” was less than trustworthy.

    How many people have died or will die because of Trump derangement syndrome.

    1. Bob TM says:

      Do you really think that entire developed world’s doctors and scientists would ignore a cheap and available medicine just because an angry old man across the pond is promoting it? He may well be the centre of the universe for his fans, but he’s seen only as a bit of a clown outside Americas.
      Myself and everyone I know wants HCQ to work, but its hard to argue for it when every reputable RCT shows it as ineffective.
      The minute we have reputable double-blind RCT that shows it as effective I will gladly admit my scepticism was wrong.

  122. JP Leonard says:

    David E. Young, MD replied to:
    “It’s called the “fallacy of authority”. You indicate that since Reich is a Yale Professor that he must be correct.”
    Or maybe he said Laura Ingraham is not an authority so it is correct?
    I was bemused to see HCQ haters now bringing up the authority fallacy, since they usually spend their time genuflecting to authoritarian idols, like Grouchy Fauci or Gruesome Newsom.
    This anomaly gives greater insight into the workings of politically correct science / Neo-Lysenkoism.
    1. Do not look at the data, look only at the conclusions and the author.
    2. If you agree with the Conclusion, then the author is an Authority and it should be believed.
    3. If you disagree with the Conclusion then it should not be believed, because the author is not an authority, or if they are one, it is the authority fallacy to believe it.

    Such a Science Authority as Forbes magazine has now beautifully formulated a canonical version of the “new” doctrine. By Astrophysics PhD Ethan Siegel, author of a book on the Big Bang and thus presumably the Expert on everything that proceeded therefrom and since.
    Siegel / Forbes have promulgated the 11th commandment:
    “You Must Not ‘Do Your Own Research’ When It Comes To Science”
    ““Research both sides and make up your own mind.” It’s simple, straightforward, common sense advice. And when it comes to issues like vaccinations, climate change, and the novel coronavirus SARS-CoV-2, it can be dangerous, destructive, and even deadly.”
    (Or when it comes to any other controversial issue of course.)
    Siegelforbes goes on to give only one side of the story about those issues, using the straw man fallacy to misrepresent the concerns of dissidents.
    No talking back aloud there.

  123. JP Leonard says:

    “Why everyone was wrong” about SarsCov2,
    By Beda Stadler, former director of the Institute for Immunology at the University of Bern, a biologist and professor emeritus.
    Main Points –
    Firstly, it was wrong to claim that this virus was novel. Secondly, It was even more wrong to claim that the population would not already have some immunity against this virus. Thirdly, it was the crowning of stupidity to claim that someone could have Covid-19 without any symptoms at all or even to pass the disease along without showing any symptoms whatsoever.
    this so-called novel virus is very strongly related to Sars-1 as well as other beta-coronaviruses which make us suffer every year in the form of colds
    the entire world simply claimed that there was no immunity, but in reality, nobody had a test ready to prove such a statement
    34 % of people in Berlin who had never been in contact with the Sars-CoV-2 virus showed nonetheless T-cell immunity against it
    if we do a PCR corona test on an immune person, it is not a virus that is detected, but a small shattered part of the viral genome.
    It is likely that a large number of the daily reported infection numbers are purely due to viral debris.
    I recommend reading John P A Ioannidis’ latest work in which he describes the global situation based on data on May 1st 2020: People below 65 years old make up only 0.6 to 2.6 % of all fatal Covid cases. To get on top of the pandemic, we need a strategy merely concentrating on the protection of at-risk people over 65. If that’s the opinion of a top expert, a second lockdown is simply a no-go.

  124. NICK says:

    Beneficial effects exerted by hydroxychloroquine in treating COVID-19 patients via protecting multiple organs

  125. NICK says:

    Impact of medical care including anti-infective agents use on the prognosis of COVID-19 hospitalized patients over time

    1. JP Leonard says:

      Re: Impact of medical care including anti-infective agents use on the prognosis of COVID-19 hospitalized patients over time
      Data rich Chinese study of 2882 patients. Those given HCQ had significantly better outcomes.
      550 were in critical condition. of these the group given HCQ had a death rate of 19% while those without HCQ (NHCQ group) had a death rate of 48%
      Professional skeptics will scoff that it’s a Chinese study I guess.

      1. NICK says:

        They are blinded by their ego! Thank for all you post.

  126. NICK says:

    Effectiveness of Hydroxychloroquine in COVID-19 disease: A done and dusted situation?

  127. Jim Parkin says:

    Coming back to this. Have you seen this sting article in a predatory journal?

    SARS-CoV-2 was Unexpectedly Deadlier than Push-scooters: Could Hydroxychloroquine be the Unique Solution?

    Now retracted due to “serious scientific fraud” as opposed to showing up the journal.

    *Very* pointed criticism

    The whole paper is gold.

    In a pre-test phase, we asked each participant in the treatment group to roll 500m in a straight line on a push-scooter. Participants who fell or died during the pre-test were reallocated to our control group (two falls, one death). It emulates the original Hydroxychloroquine paper in other parts as well…

  128. NICK says:

    @Derek . Just to let you know I really appreciate you let people with different views post. I post about SOD, GSG and NAC supplements – COULD- POSSIBLE HELP- with organ damage and listed link to support. My comment was removed. So thank you for allowing discussion!

    1. NICK says:

      Removed from different site , not yours.

  129. Walker says:

    Astounding what amount has occurred since this article was posted. The primary concern is that the Lancet needs to withdraw the article with respect to HCQ not working and having genuine reactions. Turns out the organization doing the examination “Surgisphere” was under reliable.

    The number of individuals have passed on or will bite the dust in light of Trump disturbance condition.

    Spotify Premium Trial Free

  130. vik raj says:

    The second the Impeached Imbecile expressed the word hydroxychloroquine the whole world ought to have realized this was an all out trick.

    1. theasdgamer says:

      Your TDS is showing. Impeding your critical faculties. You should take up basketweaving to calm your nerves.

      Pro tip: Hydroxychloroquine advocacy has nothing to do with Trump.

  131. Poopi says:

    I do get your point but sniper 3d is not a game to be played without that provides the best mod and I think that should be used right?

  132. e Mega Blog says:

    Nice data. I will increase my knowledge as a blogger. Thanks for sharing.

  133. Linda says:

    Thank you for sharing your great information. I read your blog daily . It give me so much knowledge and ideas.

  134. Touching victory, will have to hold on to the sniffing, never showing a winner with anyone. The name of the boxing that was set in formidable and terrifying, the disciple shook his head. คาสิโนออนไลน์Was renamed by the audience as a deep sleep disciple carrying down a boxer who lost forever

  135. TS168 says:

    English Premier League club legend Gary Neville has expressed hope that his new team-mate Wayne 918kiss Rujie is now permanent County manager. That way, it will keep the team in line with Atletico Bay boss Diego Simio, that is, making the team play as smart as Rooney was in his youth.

  136. Gclub168 says:

    It can be said that there will be continued pressure for Chelsea manager Frank Lampard following the recent lead out to Leicester City 0-2 in the English Premier League game on Tuesday 19 January. Past until making this season “The Lions Navy Blue” has lost 6 games in the league and has just kicked 19 games.
    It is true that losing to Leicester at this time may not be a bad thing to the point of a world. Because they performed so well that they were provisional leaders from their last victory, but Lampard’s team had been poor for a while, despite spending more than £ 200 million in the last summer. Until getting famous players to join the team, such as Timo Werner, Kaihavertz and Hakim Ziyek.Gclub168

  137. Manchester celebrity Paul Pokbacha said he 918kiss didn’t think he could shoot like this as he slashed a beautiful 918kiss goal that helped the side win 2-1 Fulham to the battlefield in the English Premier League. On Wednesday, January 20 the past.

  138. Diamond Green says:

    Never think it’s over to get your ex back for Lord Zakuza is here to get your ex partner back. Email him on Lordzakuza7 @ gmail. com for help.

  139. Throughout many times before Van de Beck had an Riders of the Storm outstanding performance with Ajax Krit until he was praised by many parties. But he has not been able to make a permanent starting point with Man ever since he hired to the team in the past, and there have been rumors that he is not happy with his own situation, examines and needs the team to find opportunities. More field, which may be in the form of a lease

  140. davidharper says:

    It’s a magnificent blog and it was very informative while reading. I look forward to reading more of your blogs.

  141. It is understood Newcastle United and West Bromwich Albion were in talks with Lingard’s agent, but the players had turned down an offer สูตรบาคาร่า for both teams. Before choosing to play for the “Hammer” with former Manchester United manager David Moyes in charge of this deal, it is expected that West Ham have to spend more than £ 3 million, including loan and Lingard’s wages

  142. Sam Hong says:

    so now the vaccine is out. but is it really effective? in many countries people of afraid of getting vaccines. they don’t believe that it’s a cure rather than they are sure that its bad for the health. Yeah it’s happening in many third world countries.

  143. John alex says:

    This is fascinating Surgisphere is the organization that is liable for gathering the Lancet article on Hydroxychloroquine. The science proofreader for this six-man organization is Thomas Koenigsberger, who passed on in 2018. I think this is odd. The other science proofreader is a computerized craftsman whose photograph was taken from her page. Likewise, there gives off an impression of being no information researchers on the organization’s staff accountable for gathering the information.

    1. WST says:

      ” accountable for gathering the information.”

      why bother if all data was fabricated ?

  144. After the news of Kudo Shinichi alive After a long time disappeared Spread around (Conan takes medicine to temporarily restore his body Go on a field trip to school But involved in the case) Fortunately, Conan’s real people help keep the news in time. The สูตรบาคาร่า Kudo family then gathered together to consult each other. The clue of the man who was killed by RUM before his death and the RUM code alternate until he learns that the boss is related to Karasuma Renya (Japan’s most powerful politician who is likely to die in the past). Mother therefore thought to stay in Japan to come up with a plan to find a way to help

  145. James Walker says:

    I accept that is the purpose of endorsing it inside five days of the advancement of side effects, to treat the patients preceding the improvement of ARDS, which is when a great many people are conceded to clinic.
    so now the immunization is out. in any case, is it truly successful? in numerous nations individuals of terrified of getting immunizations. they don’t accept that it’s a fix as opposed to they are certain that its awful for the well being. Better believe it’s going on in numerous underdeveloped nations.

Comments are closed.