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Hydroxychloroquine Update For April 6

There’s a lot of news to catch up on, and to keep things straight I’ll divide the hydroxychloroquine part out into this post, and cover others in the next one. My previous reviews of the clinical data in this area are here.

First up is this study from France. It’s another very small one, and all the usual warnings apply because of that. It’s from a team at the University of Paris and Saint-Louis Hospital there, and they evaluated 11 consecutive patients admitted there with the same course of treatment as the Marseilles group first reported (hydroxychloroquine 600mg/day and azithromycin, 500mg the first day and 250 mg/day thereafter). The mean age of their patients was 58.7 years, and (notably) 8 of the 11 had significant comorbidities (two obese, 5 with various forms of cancer, one with HIV). That’s a tough population, and unfortunately, the HCQ/AZ combination did nothing. One patient died (and two others went on to the ICU) and of the ten remaining, 8 were still positive for the virus by nasal swab on days 5/6 after treatment. One patient had to discontinue therapy on day 4 because of QT prolongation, a known side effect of hydroxychloroquine that can lead to fatal heart arrhythmia.

So while this is a small study and not a perfect match, it provides no evidence to show that the HCQ/AZ combination had any benefit at all. While we’re on the subject of QT prolongation, there’s this preprint from a medical team at NYU that was also treating patients with the same combination of drugs. In 84 patients, they found notable QT prolongation in about 30% of them, and another 11% were to a level (>500 milliseconds) that put them at a high risk for arrhythmia. This group’s mean age was 63, 74% male. No cancer patients in this group, but 65% did have hypertension and 20% were diabetic (which from many reports is actually a reasonable look at the patients most likely to progress to severe disease). The strongest predictor of dangerous QT numbers was the development of renal trouble while on the drug combination.

There are a couple of other things that need to be noted. One is that hydroxychloroquine itself actually lowers the activity of the innate immune system; that’s why people take it for lupus and for rheumatoid arthritis. Many people are saying that perhaps it will work best if taken early in the course of infection, but this effect (which is mediated through TLR receptors) should be kept in mind. Another potentially important point is raised in this preprint – which, it has to be said, is not human data but mouse toxicology. But with that in mind, the authors report what looks like a bad interaction in that species between HCQ and metformin. And by “bad”, I mean about 30% mortality. If this translates at all to humans, it could be bad news, because (as mentioned above) diabetics look like a high-risk group and many patients may well have been taking metformin when they present at the hospital. We need more information on this. An investigational drug combination that showed this effect in mice would not move forward in the normal course of things.

Finally, I would like to point out this preprint from a multi-country team (Denmark, Netherlands, UK) which goes back over the original Marseilles report and reanalyzes its statistics. The problems that many noted with that paper show up in detail here, and the lessons that you take from it can vary a great deal depending on the details that were not well reported or characterized:

Performing a Bayesian A/B test, we found that for the original data, there was strong statistical evidence for the positive effect of HCQ mono improving the chances of viral reduction when compared to the comparison group. However, we found that the level of evidence drops down to moderate evidence when including the deteriorated patients, and it drops further to anecdotal evidence when excluding the patients that were not tested on the day of the primary outcome (day 6). For context, anecdotal evidence is generally considered ‘barely worth mentioning’ (Jeffreys, 1961) We were able to qualitatively reproduce the finding of an improvement of HCQ +AZ over HCQmono . However, although this finding was statistically significant in the original finding, our reanalysis revealed only anecdotal evidence for the positive effect of HCQ +AZ over HCQmono . However, when we included the deteriorated patients into the analysis, this evidence increased to moderate.

It’s no wonder that this work has set off so many arguments: statistically, it’s like a funhouse mirror. Here, though, is where some of the folks pinging me on Twitter and sending me emails tend to get more worked up, especially to that point about anecdotal data. I can see where they’re coming from: if you haven’t done this stuff, you can look at a report of people responding to such a treatment and figure that the answer is here – right here, and anyone who doesn’t see it must have some ulterior motives in ignoring what’s in front of their face. But that’s not how it works.

It’s weird and startling, though, if you haven’t had the opportunity to go back through clinical research (and even patient treatment) and seen how many things looked like they worked and really didn’t. It happens again and again. Alzheimer’s drugs, obesity drugs, cardiovascular drugs, osteoporosis drugs: over and over there have been what looked like positive results that evaporated on closer inspection. After you’ve experienced this a few times, you take the lesson to heart that the only way to be sure about these things is to run sufficiently powered controlled trials. No short cuts, no gut feelings – just data.

What do I mean by “sufficiently powered”? That gets to the concept of “effect size”, which is something that most people outside of medical research probably don’t spend much time thinking about. One of the favorite arguing points that I get sent my way is “You don’t have to run a controlled trial to see that parachutes work! What are you going to do, take up a planeload of people and toss half of them out without a chute to prove your point?” Ah, but the effect size of having a parachute at 10,000 feet is very, very large. And the larger the effect size, the smaller a trial can be and still have meaning. In drug research, though, we do not approach parachute levels of difference very often. Drugs help some parts of the patient population, to varying degrees, whereas a parachute helps every single person who’s tossed out of a plane (and the result shows up in a very hard, dramatic, and easily measurable endpoint!)

It may seem like the Covid-19 epidemic is more like the parachute situation, but consider that many people get infected with the virus without ever really knowing that they’re sick – which is not the case with being heaved out of an airplane, for the most part. Most of the people who get the coronavirus survive – the fatality rate is of course being argued about, but is probably in the 1% range, give or take. Now, from a public health standpoint, that’s an awful figure, ten times as bad as the seasonal flu and with a more infectious virus as well. But for figuring out therapeutic options, it’s tricky: if most everyone will eventually recover with the current standard of care, how do you test your new idea?

Well, you have to look at disease progression, for example: how many go on to the ICU, how long they’re in the hospital total, and so on. These are very important things to improve, and you’ll notice that these are patient-centered endpoints as well. Ideally, that’s what you want, as opposed to surrogate endpoints – in this case, viral load would be an example of one of those. You would think that viral load would correlate with the patient-centered ones, but that has to be proven and it might not be as tight a connection as you would like, either. As more studies collect such data you can start to use surrogate endpoints once you feel that they’re useful, but you should never just assume their utility up front. What counts in this epidemic is how many people get sick, how sick they get, and how quickly they recover. There are a lot of variables involved in all of those, and we need a lot of quality data to see what’s really going on.

One more point: someone last night was trying to tell me that my job was to “bring people hope” and that my attitude wasn’t helping with that task. Let me clear that up. I am not a physician, and I am not a clinician. I have spent my career in very early stage drug discovery, not at the bedside. Unfortunately, my lab skills are not well matched to the current epidemic – my own research has been more oncology-focused, and it’s way back in the pipeline. None of the last three companies I’ve worked for currently have any antiviral research. So as for my contribution to fighting the coronavirus, well, you’re looking a significant part of it right now. I can curate and annotate the news, add my own opinions after thirty years of drug discovery work and (I hope) make people smarter about what’s going on.

But keep in mind, most of what I’ve done, the great vast majority of what I’ve done over that thirty years has not worked in the clinic. Most things don’t. My job as a researcher has not to been to raise people’s hopes without data in hand, my job has been to try to produce such data so as to raise hopes with some reason to do so. When I see something to be hopeful about, I’ll say so, and when I think people are getting ahead of what we know, I’ll say that, too. Go back to the first things I wrote about the hydroxychloroquine/azithromycin work: I called it “potentially very interesting” and called for more data to see if it was real. That’s where I still am. Raising hopes just for the sake of raising hopes is not where I am, though, and in fact I find that whole idea to be cruel. We’re going to defeat this virus, this epidemic, by being as hard-nosed as we can be about collecting real data on real-world outcomes as quickly as efficiently as we can, not by talking vaguely about miracle cures and isn’t it something and wouldn’t it be great. You’ll need to go somewhere else for that. Try Dr. Oz, he’s good at that crap. I’ll stick to what I’m good at here.

Update: the society that publishes the journal where the initial Raoult report appeared has stated that the paper does not meet the standards that they expect.

Update 2: some Swedish hospitals are reporting that they have stopped administering hydroxychloroquine and the HCQ/AZ combination due to lack of evidence and worries about adverse reactions.

435 comments on “Hydroxychloroquine Update For April 6”

  1. Michael says:

    I fully agree (I am in clinical trials, too).
    Also very important and often forgotten: Do no harm in the course of trying to help people. Doing this uncontrolled testing will put a lot of people at risk and do nothing at best. It might kill people indepently from the outcome of their CoVid-19 disease at worst.
    If I talk to people about this point, then they are suddenly not so eager anymore to try out some untested (for this case) drug.

    1. I say to the naysayers, if you were a Covid19 patient, would you want to try the Oxy Cocktail?
      I say, “absolutely yes”. No equivocation!

      1. des says:

        And I say absolutely no. If I were in hospital with COVID-19, I would not accept HCQ without solid clinical evidence of its efficacy. I’m not even sure I’d agree to participate in a clinical trial, because I am predisposed to some of its known adverse side effects.

        This is the “atheists in foxholes” fallacy, by the way. You are so convinced of the soundness of your own reasoning that you assume that everybody will eventually reach the same conclusion as you.

        1. Dr. Know says:

          It would be interesting to poll it with actual patients. I bet 90%+ woudl opt to take hydroxychloroquine

          1. Henry says:

            If I were critically ill and at significant risk of death? Yes, I’d agree to be given it. And indeed, it is approved for such cases by the FDA.

            Otherwise? No, I wouldn’t agree. I’d want the other standard methods first. If those fail to help me and I’m not improving or getting worse, I would probably agree to hydroxychloroquine or perhaps some other experimental drugs – but only in that scenario.

          2. Eric says:

            A large majority may agree to take it. However, humans are terrible at risk analysis when they have the details, and we don’t have the details of this treatment. Further, many will survive, even if their treatment plan involves respirators. Covid19 isn’t necessarily a death sentence, so I suspect many would take the approach of “I should be fine”…

          3. Dave says:

            That’s because 99% of people have no clue how to interpret the “evidence” and cannot understand that at this point HCQ is just as likely (I think more likely) to kill or harm you as help or heal you.

          4. In Vivo Veritas says:

            Friend, please recall that the large majority of women offered thalidomide took it. Suffering patients are not reliable sources of risk evaluations.

          5. Mantas says:

            It most likely works earlier in the infection, and every drug works better in healthier populations, so it should be given as first line therapy.
            Unless you want to die.
            Don’t forget zinc!

          6. Mustafa says:

            Yes – we are patients and we opted in. It’s easy to sit behind glass walls in a lab and make statements on patients’ feelings and sufferings. While the lazy scientific community is testing ideas people are suffering and dying in tens of thousands. While this is “statistically” is insignificant to scientists, each of these patients is someone to somebody.

          7. Bob Fischer says:

            The notion that “many will recover” if on ventilators is wrong. The best scenarios (if they are to be believed) were from China where about 30% of patients on vents recovered. In the US, that figure has been quite a bit lower, more like 15%, which means most people on vents will eventually succumb. Anecdotally, many of my nurse friends say they have seen few if any patients recover once on the vent. In this scenario, as much I as must vehemently disagree with the President’s poorly thought out and ill-conceived sponsoring of HCQ, it seems worthwhile to try it on patients on vents; you may consider them “terminally ill”.

        2. Super Genius says:

          Easy to say in the comfort of your (currently disease-free) existence! I hope you’ll edit this post, while you still can, if it should come the time, God forbid, when you’re being hooked up to the ventilator in the ICU. (Actually, based on reports in the field, you may not want to wait that long.)

          By the way, I and my entire family took HCQ during a two-week trip to Kenya as a malaria prophylactic. No one bothered to warn us of all the dire side effects.

          1. CRAIG OSTFELD says:

            What was the regimen you used? I’ve taken it, but it was quite a while ago, for a trip to Africa. It seems like I took some a couple of weeks before going, and then after I came back. But I believe it was quite a bit less than is proposed for this virus.

          2. jeepgirl5 says:

            Right – you took it for its proven purpose. Which means nothing in this context.

          3. KonaJoe says:

            For malaria prophylaxis the dosage is 500 mg once a week. Dosing regiment for CV is 200 mg twice daily for usually 7 days. So you get 1400 mg for CV over a week vs 500 mg as a malarial prophylaxis. Higher dosage can lead to QT elongation and heart rhythm disorders, but usually only if you already had underlying issues. Lupus patients take the same dosage as CV patients – pretty much forever. And BTW, HCQ is used much in Africa as a malaria prophylaxis due to most strains common there having developed resistance.

        3. John Strong says:

          Which is why we should return sovereignty to the individual when it comes to health decisions. You should be free not to use HCQ. You should not be free to prevent others from using it.

          1. Spencer Stang says:

            Agreed! Nothing sets me off faster than people debating on how a patient should be treated without accounting for the patient’s opinion. I’m also okay with doctors saying that they won’t do what the patient wants. I’m not okay with bureaucrats telling the doctors AND the patients what they must do in a given situation.

          2. caron masucci says:

            Please note that hydroxychloroquine has been around since 1955. Before COVID 19, QT interval prolongations were not associated with its use. It could be the result of concurrent therapies With hydroxychloroquine (drug interactions) or the patient could be suffering from heart damage due to the illness itself (Dr. Erin Donnelly Michos, Johns Hopkins Medicine). When treating a novel virus, it’s difficult to anticipate the outcome.

        4. Daniel Balfour says:

          You’re so “open minded” your brain fell out.
          Glad there will be more HCQ around for those who actually want to get better.

          1. Windriven says:

            Have at it, genius. There are much better drugs for managing cytokine storms and that is the only relevant use – unless you happen to have malaria as a co-morbidity. But hey, I’m sure you know lots more about biochemistry and molecular biology and virology than all those pointy-headed researchers.

        5. Tag says:

          “I am predisposed to some of its known adverse side effects” Then you would not be prescribed HQC! All existing contraindications still apply.

        6. Brendon says:

          It’s odd how everyone seems to feel like they have to speak for everyone else. Those that don’t want to take it… Don’t. No one is going to force you. And those who are happy to risk it after a discussion with their doctor are free to do so. My life, my body.

          This ridiculous attempts at social media paternalism everyone is exhibiting is tiring at best, and only reveals deepseated insecurities masquerading as a show of toughness… Meaningless posturing.

          I also call utter BS on your claim that you won’t take it after days of drowning in your own body staring at a ventilator. Especially when you suddenly realize it’s neither courageous or clever to lie and rot away like a sack of flesh all by yourself without even trying to do something about it. Pascals wager is the clever way to approach such situations.

          1. John says:

            “My life my body” –except perhaps when it affects other people.. It is almost impossible to find plaquenil for its proven purposes. I have lupus and finally found one drugstore that could get the medication. My insurance company now limits the number of pills it will cover. I had to pay 12 times what I paid just a few months ago for a 90 day supply. This DOES make me angry. There are many of us who rely on plaquenil – I have long called it my “miracle drug”. Without it, I am very very sick. With it, I can function.

          2. Mary Jo says:

            Having seen the numerous reports from doctors using these drugs as a last resort in the ICU… they do not work. What possible therapeutic benefit they *might* have appears to be much earlier, well before someone needs to be on a ventilator. So if you want to roll the dice and hope they help more than harm, don’t wait until you’re on a ventilator to do it.

          3. Joe says:

            If i am unfortunate enough to be on a ventilator, I want remdesivir, not HCQ. Per study published in NEJM, I have a better chance of survival

          4. Pastor Doug Joseph says:

            “And those who are happy to risk it after a discussion with their doctor are free to do so. My life, my body.” — Sadly, for many, no — they are *not* free to do so. Many state boards of pharmacology have barred it being prescribed for CV. In many places an agreement of both doctor and patient cannot get the medicine to the patient, no matter how much informed consent exists.

        7. Tommy says:

          I absolutely agree with Des! The area that is not being discussed is a legal one. As much as we like to say that the legality of treating a patient with an unproven medication is fine with patient approval, it can be a serious problem. When a provider gives a patient a drug in an off label treatment the risk high for both the patient and provider. Part of the problem is the patient’s state of mind and the opinion of the family/significant others. Let’s say the patient demands the drug and the provider agrees to give it to patient after a consent form is signed by the patient and correctly witnessed. If patient die, the family/significant others may sue the provider, facility and whoever else they can think of. It happens. I took care of patient who had a DNR and specific instructions to allow death naturally at home. The family demanded that EMS resuscitate and transport the patient to the ER. Once there the family member, who rode with the patient in the ambulance, demanded treatment until the medical director of the ER informed the family that the patient was being kept alive artificially. The family then demanded that the patient be taken to another facility. EMS complied. After the patient left I asked why the patient was resuscitated when there was a DNR on file. The answer was that the patient wouldn’t be there to defend the provider and the facility from the possible litigation. The same applies with off-label use and subsequent death of the patient. Who will be present to say the patient was of sound mind and the provider didn’t act recklessly?

        8. KT says:

          It’s easy comment like that when u are not in the fox hole.

        9. Rich D says:

          According to WebMD, 1 in 5 prescription drugs are off-label. That’s a lot of doctors prescribing a lot of drugs without the benefit of a clinical trial.

        10. M says:

          If you are predisposed then I’d assume your doctor would be smart enough to eliminate this treatment as an option for you…so you wouldn’t be considered a candidate to start. Everyone is responding as if the decision is theirs when a physician must evaluate the individual risk factors before considering ANY drug to give a patient.

        11. Meltdown56 says:

          Every aspect in this debate is a clinical shared decision between the provider and that patient . It upsets me to see such a debate around the science and the politics that this drug has elicited. The plethora of opinions is overwhelming. For every expert opinion who opposes I can show you expert opinions who support . Such is the way in medical science and has been for a very long time . It all boils down to CHOICE. I’ve seen friends who had good success with last line chemo agents but experience severe organ damaging effects switch to experimental new treatments that did no work leading to fatality . Again . This is that shared choice . We all assume risk is some way.if that doctor / patient want to use the drug, they make that choice and assumption of risk . Everyone has their opinion but in these unprecedented times, desperation and fear lead to quick decisions of hope.

        12. Dr. J Howell says:

          The pneumonia, clotting disorder, renal disease, myocarditis, and ventilator care come late and after the therapeutic window, much like gram negative septic shock. No antibiotic is efficacious after the window of opportunity. This virus is a killer if you let it. The fool who wrote this article has no idea what this virus does or how to mitigate it. He admitted that. His waffling with his numbers sounds like he’s hedging his job as a reviewer. Pure BS.

          1. marelyn eve shapiro says:

            Hello, I’m not being a smart-ass. I’m looking for hope. Are you an MD? I hear you saying to take it sooner than later. But what about a statement that it lowers your immune response?

          2. Thomas O'Ne says:

            Well said, the fool who is not an expert discredits HCQ ignores the successes. Doctors are using it with success although there is not an exact clinical explanation beyond its success. The writer of the article along with the amateurs anchors on Bloomberg along with the other so called fake news outlets who seem to be waging a propaganda war against Trump and against the USA. Listening to their spin is sickening. Somone is lying and has blood on their hands

          3. Patrick Jewell says:

            The fool who wrote this comment is clueless to the fact that Hydroxychloroquine is NOT in any way, shape, or form an antiviral medication.
            Hydroxychloroquine is a zinc ionophore.
            It is literally a synthetic “doorway” (transporter) that allows extracellular zinc to pass into the cytoplasm, so the ZINC can destroy the virus. THE ONLY SCIENCE HERE, IS THAT ZINC IS THE ANTIVIRAL. Your cell membrane has naturally occurring membrane transporter proteins specifically for zinc, called zip proteins. A zinc ionophore’s function is to create additional passages into the cell for zinc. This enables a cell to load up with zinc faster, than it normally would. Quercetin (another ionophore) and CoQ10 perform the same function as Hydroxychloroquine, without any toxic side effects. The study cited, can not stand up to scrutiny. It was not a double blind study. The test group was significantly younger than the control group. Death occurred, disproving any efficacy of the “findings”. Numerous people that started the study, were removed from the final data. The list goes on. Other double blind studies were conducted in two separate countries, and found “anectdotal” results at best. Currently, Doctors are prescribing 220mg of zinc sulfate (5 x RDA), with Hydroxychloroquine to FALSELY “prove” HCQ is an antiviral. Zinc has been proved for decades to inhibit intracellular viral replication, with or without supplemental transportation assistance. Without ZINC, Hydroxychloroquine is ineffective in fighting a virus.
            Hydroxychloroquine is NOT an antiviral, neither are any other ionophores, or zip proteins, or Coenzymes. Anyone can research ionophores (synthetic and natural), and ZIP proteins as well, to verify my claims. Synthetic ionophores are a way for pharmaceutical companies, and Doctors to make money, mimicking a natural product that can be purchased without a prescription, or Doctors visit.
            Please people, do your own research. Start questioning all the disinformation and pseudoscience that gets passed as fact by our so called “experts”. And for Christ sake, stop trying to claim you are an expert, talking about how great of an antiviral, Hydroxychloroquine is.

          4. John Garcia says:

            Concur Doc, 100%.

          5. NILSON ANDREIS WITKOSKI says:

            Hydroxychloroquine + azithromycin are being used in Brazil, Italy, Spain with great success: mortality rates having been reduced from 20% to 1% in hospitals prescribing those between the 2nd and 5th day of appearing the first symptoms of COVID-19.


        13. If I, or one of my loved ones, was in a helpless situation in hospital with death CIVID-19 infection and all other treatment measures had failed, I would cost certainly give hydroxychloroquine a try, and would suggest it for critically ill loved one.
          Although I am in faraway Australia, I well know it pains many Americans to hear Trump’s name, but he has correctly said, ‘What is there to lose?’ in such dire situations. There is certainly no time to wait for the completion of a classic trial, which could take up to 18 months or even longer, and may produce nothing at all.
          I suspect many of the objections to this drug are actually driven by the widespread, uncompromising liberal hatred of Trump.
          I also wonder if we’d be having this discussion if Barak Obama had “touted’ hydroxychloroquine (I think not).

          1. marelyn eve shapiro says:

            I despise zTrump. I got a script for Hydroxycloroquine 2 weeks before he brought it up and taked with hope on my wall. It is unfortunate the his name is associated with it however he pushed through a huge observational study in Boston and flooded NY with the drug. Then of course it makes sense because he has connections to the company.

        14. Nunya says:

          Would you let them put you on a ventilator? If so, can you point to the completed study showing the efficacy of using a ventilator to treat COVID-19?

          1. Kim says:

            Best comment here.

        15. JD says:

          Say that to the people who are dead. You wouldn’t take it because there’s no efficacy? Hello. It’s a new virus, a new disease. NOTHING IS PROVEN. You are just another pretentious pseudo-intellectual.

        16. The Admiral says:

          …lets ad to your statement, “…and on a ventilator…”

          Once someone is intubated, their prospects for survival drop by 50% or more.

          Those with a large clinical pool of patients who have received this protocol, are primarily “high risk” people, and the goal is to treat them prior to getting to the hospital. Everything changes once a Covid-19 patient reaches the hospital.

          I’ll tell you this, if media did their damn jobs and published death/survival rates of those who have been hospitalized, this demonizing of the HC/Zn/Zith protocol would be hushed up pretty quick by the outrage of Americans.

          Those opposing the protocol despite rapidly growing clinical results information, should be investigated for conflict of interest. You will find some, who will be in legal jeopardy of getting Racketeering and Influence Peddling (RICO) charges… and I HOPE THEY DO GET THEM

        17. Jordan Velez says:

          Myself and all of my workers have all been diagnosed with Wuhan COVID-19. There were 6 in total and of those who took the combination of HQC with Azithromycin and Zinc Sulfate are all back to work with heaviness on the lungs still remaining but all negative test results after fighting the virus. The one who did not is still sick. I know it is a small test pool and there are other weighing circumstances. However a 5 to 1 ratio is still pretty good in my eyes. on a side note I also gave it to my mother who’s 69 years old her oxygen levels got down to 7% on the finger tester she was brought to the hospital put on oxygen and immediately given hydroxychloroquine combination. The next day her oxygen levels had increased dramatically and a lot of the effects of the virus were starting to diminish. So for those that are on the opposite end of the spectrum maybe It isn’t being administered properly. Because it seems like it works.

          Nationwide Study Finds Malaria Drug Touted by President Trump Led to More Deaths, No Benefits in Coronavirus Patients! <——LOOK AT THESE RESULTS! — SEMPER FI!

        19. Al Dezotell says:

          200 mg of HCQ is plenty and that’s not every day Aretha Myson is in the zinc

      2. Crystal says:

        If I were a COVID-19 patient, no I wouldn’t want the quinolone azithromycin combo. That is unless they offered an antiviral with it. If the pneumonia is secondary to the viral infection and it’s bacterial sure give me the combo but you are not administering it to me without the antiviral and vitamin c iv therapy. I would think whatever the antibacs are doing to help just gives the virus more room to play. That virus needs to be weakend at the same time the antibiotics are being administered. If their purely treating a virus with antibacterials, what is it doing that helps with recovery??? How is an antibiotic and quinolone that is used to treat bacterial or parasitic infections going to be effective in treating a virus????? What does it do??? I think it’s going to add to resistant strains of bacteria wich could potentially cause more harm than good. Please enlighten me on what it is about quinolones and azithromycin that your looking at( the action of the meds?)? I’m not a Doctor nor a Pharmacist however, I spent a number of years in the medical field. So I may not be educated enough to understand the complete action of these drugs. Is the Drug company benefiting from this through possible financial dealings with our President? I’m seeing a lot of things handled by this administration that I’ve never experienced before in my life. There’s a lot of throwing large corporate names around here. If this is solely to benefit a drug company due to financial interests and during a major crisis, shame on all involved. I’m very curious For answers.

        1. Crystal says:

          I just left a reply and forgot to add that I think zinc would be effective in combination with maybe the quinolone/zithro combo along with ANTIVIRALS and vitamin c iv therapy.

          1. Tom says:

            If my understanding is correct a Zinc supplement is required for most effective results. I believe what they’re seeing in the unreliability is due to the patient’s natural zinc supply. IIUC/AFAIK, the HCQ is used to transport Zinc into the cell and it’s the zinc that stops viral replication. This would make studies that don’t include a zinc supplement highly variable as if this mechanism is working as expected, it would highly depend on the availability of zinc within the patient’s body.

          2. Brad B says:

            It is so encouraging to finally see (hear) the educated and resourceful segment posting here talking about the role and value of Zinc Sulfate in the HCQ regime. Please do not stop spreading the word as this whole HCQ thing has become so politicized. Thanks to all…

          3. Steven Howard says:

            Life Extension recently published an article supporting a zinc acetate regimen as more effective than zinc sulfate.

          4. alexa kinney says:


          5. JayR says:

            Response to Crystal re does the President benefit financially by promoting HCQ has been addressed by Snopes, not know to be a Trumpster site: . As a line of disagreement against HCQ it should be dropped immediately. It only undermines any other argument to include financial benefit to the President.

          6. Kayla says:

            Hi there,
            I do not know the science behind the differences in zinc gluconate/sulfate etc. outside of the fact that some have larger amounts of elemental zinc. The only zinc that I could find was zinc gluconate and zinc picolinate. Would these be sufficient or is there something specifically about zinc acetate and sulfate that makes them work better? Seems people here may know better.

        2. CJ says:

          Crystal, some maccrolide antibiotics have an interesting property when it comed to fighting viruses. They may actually help the body to fight viruses. I.e.,

          So, if I was triaging a patient with lower respiratory viral disease, I would probably offer azithromycin whether or not an additional specific anti-viral was available

          1. Crystal says:

            CJ Thankyou for your response. Being someone who has worked in the medical field mainly seeing people infected with sti’s, but not holding a degree in a specific area of study leaves me educated but not enough. So I do appreciate your response in helping me understand how these drugs work.

          2. KarenLL says:

            CJ, interesting, thank you for posting the journal link. I have to ask though, I read the article and all of that research was conducted in vitro. The authors themselves even say that they need to confirm their findings in vivo. I’ve never heard of antibiotics being effective for viral treatment. Do you know if this has been verified in vivo? Thank you very much again.

          3. Jan says:

            In 1999 I was intubated for asthma excerbation after 2 weeks of doctor trips and different asthma meds with no improvement. Luckily came out of it. Ever since then I advocate for azithromycin
            (after getting it once) because it definitely stops my asthma. Docs usually don’t want to give it. Haven’t needed any in 2 years and pray I stay well.

        3. Joe says:

          HCQ has been around since the 50s, and has 12 generic manufacturers. It won’t move the needle on a single stock.

        4. Tom says:

          Hydroxychloroquine is a zinc ionosfer. Studies have found that Zinc in the cell will not allow covid 19 to reproduce. myacins have been found to also inhibit viruses from attaching to cells. That is why they are being prescribed for this, not for their antibacterial properties. Thus treatment earlier with these drugs may keep patients from becoming seriously ill. Once the patient is already seriously ill, there may be too much virus to overcome.

        5. alexa kinney says:

          I totally see your point Crystal.

        6. Carol says:

          To your point on the “financial benefits to the President” – they are documented by CNN Politics, Bloomberg and (Motley) Fool, amongst others, as being: his ownership in Sanofi and Gilead stock.

          1. Meltdown55 says:

            Pretty much anyone with a diverse portfolio has pharma/ biotech stocks
            Let’s not throw stones

          2. chemist says:

            what financial benefits will a billionaire get from promoting a generic decades-old drug, you dumb sack of crap?

          3. Thomas O says:

            His trust has a few shares of Sanofi worth $1,305. Hew likely does not know. I also saw reports that the HQC as donated free. There truly is a deep state and the most corrupt power in our country is the media. To be president a hand full of media elites get to endorse or destroy who should be a candidate in our system. Only about 200 big wigs , with oversized egos get to choose for us. He does not have an interest, His business interests are suffering more than most, Being president has cost him, the benefits to his DC location are outweighed by boycotts of his business. He is not in it for the money . Hillary was.

          4. Barbara says:

            It’s a generic drug. It’s ridiculous. Plus much is donated. Stop spreading this crap

      3. Crystal says:

        If I were a COVID-19 patient, no I wouldn’t want the quinolone azithromycin combo. That is unless they offered an antiviral with it. If the pneumonia is secondary to the viral infection and it’s bacterial sure give me the combo but you are not administering it to me without the antiviral and vitamin c iv therapy and zinc. I would think whatever the antibacs are doing to help just gives the virus more room to play. That virus needs to be weakend at the same time the antibiotics are being administered. If their purely treating a virus with antibacterials, what is it doing that helps with recovery??? How is an antibiotic and quinolone that is used to treat bacterial or parasitic infections going to be effective in treating a virus????? What does it do??? I think it’s going to add to resistant strains of bacteria wich could potentially cause more harm than good. Please enlighten me on what it is about quinolones and azithromycin that your looking at( the action of the meds?)? I’m not a Doctor nor a Pharmacist however, I spent a number of years in the medical field. So I may not be educated enough to understand the complete action of these drugs. Is the Drug company benefiting from this through possible financial dealings with our President? I’m seeing a lot of things handled by this administration that I’ve never experienced before in my life. There’s a lot of throwing large corporate names around here. If this is solely to benefit a drug company due to financial interests and during a major crisis, shame on all involved. I’m very curious For answers.

        1. Magomed Khaidakov says:

          We are intellectually beholden to what is implied by the name. Chair means chair but it also could be a weapon, weight, table, ladder etc.. Antibacterial is just a name. For sure this antibiotic has multiple interactions, functions, and effects that may be related to counteracting viral infection. For example, antimalarial HCQ inhibits endocytosis and this can be directly related to reduction of viral load. We live in a Plato’s Cave world.

          1. Andrew Houk says:

            I think the antibacterials are there solely to eliminate opportunistic bacterial infections in virus-damaged tissue, which could be very important clinically. I don’t think they have any direct action against the virus whatsoever.

      4. johnnyboy says:

        Looking forward to the day when this Covid stuff is over and all the crazies have gone to pollute some other corner of the net with their inane comments.

      5. Frank StLicar-Phillips says:

        I’d say no freaking way. Accept I would use the word freaking it lacks literary and emotional merit. I’m the md PhD² – invented the mri for Siemens back in the day. A few other things along that line. Born in Boston. I’m first a scientist and the data is the data. And the data is lousy. One then can’t assume it means anything you want. I feel like I’m at the fall of the Roman Empire and many good things are about to be lost.

      6. Brian Ahier says:

        Agree with the point that a very sick person who is gasping for breath and on the verge of death might have a statistically different viewpoint.

      7. So all these Dr’s that claim to have used hydroxychlorogine with Z pac with obvious good results are 1 lying.
        2. Purposely giving false hope?
        3. Data isn’t equal to verbal confirmation.

      8. alexa kinney says:

        I completely agree. I think the pharmaceutical companies are trying to squash these results because they want to come up with a much more expensive drug.

        1. drsnowboard says:

          You are entitled to your opinion, it’s wrong, but you are entitled to it.
          I could similarly call out the commenters fervently advocating ZINC ZINC and ask if they are employed or hold stock in the supplements industry? Because there is an industry that relies on a lack of data and trusts in the laypersons belief that to take something is an improvement over not taking something…

          1. theg9 says:

            I think there are a few things wrong with your assumption:

            1) Do you seriously believe people are going to be profiting from zinc supplements? There are probably hundreds of manufacturers of zinc supplement pills, so there is not a “monopoly” effect of one company, or a small number, controlling all the production. Second, it’s enormously cheap relative to other pharmaceuticals. So this disproves your assumption that people are commenting about zinc because they want to make money from it.

            2) The reason it is being brought up is because it has been shown to work by several doctors that are treating coronavirus patients. According to the proposed theory, the zinc is what inhibits the RNA-dependent RNA polymerase enzyme characteristic of this group of viruses, and they chloroquine compound (or other similar compounds) work as ionophores to promote zinc transport into the cells, more than what occurs by natural transporter proteins. Even now, people have not concluded why exactly the hydroxychloroquine has been shown to have (some) effectiveness in treating Covid-19. This is just one theory for the proposed mechanism of action. If you disagree with this theory, then let us know why and let’s hear which theory you support more. The reason people are talking about it is to raise awareness about this mechanism, so proper clinical testing can be done, and then we can all analyze the data. But before we get to that stage, we have to spread the word about this theory first. That’s all there is. There is no sinister agenda by your implied shadowy “Big-Zinc” lobbying group. Lol.

          2. drsnowboard says:

            @theg9 Supplements are a billion dollar industry almost entirely based on marketing without any need to demonstrate efficacy. Of course people are going to benefit from promoting zinc supplements. When the tide comes in , all boats rise… And in an industry that is entirely based on perception and very little hard facts – and I say facts as a properly run clinical trial rather than a bunch of ‘the witchdoctor said zinc and I felt better’ anecdotes.
            It may be that zinc deficiency plays a part in the aggressive nature of COVID-19. It may be , you don’t even need the chloroquine or the hydroxychloroquine , you just need the zinc. But show the evidence, not the hype.

          3. Lol says:

            Or just have some oysters with your G&T.
            While sunbathing. Nekkid.

      9. Tracy says:

        I agree with you, Richard

      10. artisan002 says:

        When it’s a known immunosuppressant? Not just no, but hell no. When your immune system is already under attack, the last thing anyone should even suggest is something that hampers it even more. This is naysaying with logic, not yeasaying because of emotion.

        1. Zephir says:

          Immunosuppressant means, it suppresses cytokine storm, which is main culprit of Covid-19 death for elderly patients. It has good meaning to apply chloroquine then. Chloroquine is also toxic for virus in vitro – another reason for it. Third, chloroquine is ionophore i.e. intracellular concentrator of zinc, which also suppresses virus replication – a third reason for it. And the fourth: it makes alkaline and hostile the cell organelles, which coronaviruses use for replication. We could doubt all of it, but this what reviews say..

          And at the end: chloroquine is cheap generic drug easily available in large quantities. Which is actually main reason of all discussions about it here and there instead of actual testing: it doesn’t promise much profit for Big Pharma. Chloroquine for Big Pharma is something like the cold fusion for tokamak research: maybe works, maybe not – but it shouldn’t be definitely here… 😉

      11. Salome says:

        Absolutely not. The use of an untested drug, a drug that the medical community warns against its use for COVID 19, a drug that is being pushed by Trump NOT A DOCTOR is reckless and dangerous.

        1. Vaclav Subrt says:

          It is not untested drug. It is just experimental drug as to covid-19 treatment, which by definition must be every drug used as it is a new disease.

      12. Tom Smith says:

        That’s just silly. I’d say give me remdesivir – still very early days but actually has an MOA that makes sense and hints of activity.

      13. Will says:

        Absolutely! Hydroxychloroquine was approved for medical use in the United States in 1955. It is on the World Health Organization’s List of Essential Medicines, the safest and most effective medicines needed in a health system. In 2017, it was the 128th most commonly prescribed medication in the United States, with more than five million prescriptions.
        Many doctors are reporting positive results. Very few reports of serious side effects.

    2. Ben Caxton says:

      Uncontrolled studies are of little value.
      An uncontrolled study of 11 “consecutive” is even less likely to offer evidence in any direction.
      This blog article is baseless according to it’s own criteria.
      No useful information at all, but has a great clickbait headline.
      I want my 20 mins back.

    3. Super Genius says:

      There is now widespread reported use of some combination of HCQ, azithromycin, and zinc (no doubt with other medications as well). Many of these have shown encouraging results. One may still be hesitant to credit these as a breakthrough, but I ask you – where are the reports of widespread harm and death? Of any harm or death due to this treatment? The number of patients having received some form of this treatment is certainly well into the thousands.

      And it’s not like there’s no scientific basis for considering HCQ (and Chloroquine) as a treatment. In 2005 several CDC (!) researchers published a study in Virology Journal titled ‘Chloroquine is a potent inhibitor of SARS coronavirus infection and spread.’ (SARS being a similar virus to Covid19.)

      1. Some idiot says:

        Swedish hospitals have stopped using it due to side effects. So I guess they weighed up the positives and negatives.

        1. Jack Howarth says:

          The Swedes stopped testing chloroquine, not hydroxychloroquine which has much fewer side effects. It would be interesting to know if the Swedes went with chloroquine because they had trouble getting stocks of hydroxychloroquine.

      2. Otto Mann says:

        “… widespread reported use…” Have a good source that catalogs these reports? Or how about some links to a few of these reports. I’m curious, but can only find the French, Chinese, and NYC reports. Thanks.

      3. Will says:

        Very few reports of serious side effects. Many reports of success in the Treatment of the virus. The only argument against using Hydroxychloroquine is that the President spoke positively about it.

    4. Paul Williams says:

      I can’t believe this study of cancer and HIV and obese patients, of which 10/11 of them lived, is being used to say the treatment did not work. 2/11 completely cleared the virus in 6 days. Where is the data on how much the viral load was reduced. If they got down to 20% or so remaining, that is still very close to being cleared. But none of this data was presented.

      This study is actually solid evidence that it works. We should have lost 3 or 4 of these patients in that time-frame given their conditions.

      1. Andy says:

        This magazine has become biased against anything hydroxychloroquine related and has gone downhill from recent years and Just stick to their research articles instead.

        1. loupgarous says:

          Think it might have something to do with their name? As in “Science”?

          “Anecdotes, Nonvalidated Theories and Avoidance of Controls Magazine” is down the hall.

      2. alexa kinney says:

        You’re right Paul

    5. Mani says:

      I grew up in India and we used to get malaria every year like we get flu in US. I used to keep this medicine stock all the time and every season was taking without going to doctors since I knew this medicine does not hurt. Most of people Asia and Africa taking this drug without any death. So what are we loosing here if you have good chance of dying without it ?

    6. Michael Mantion says:

      IF this is a real study than someone needs to lose their medical licence. HCQ is know to slow the spread of the virus and allow the immune system to win the race and produce anti-bodies to keep the virus from infecting the patient. First The dosage of HCQ is much higher than I have ever heard being used. It seems like 200mg/day for an adult is an effective dosage. Maybe you woudn’t have had QT prolongation if you used a reasonable dosage. Some doctors use 400mg first day 200 after, some have used 800 first day 400 after. Anyone know of any treatment protocol for HCQ that calls for 600mg/day for any disease?

      The real problem with the study is they used patients who already had serious harm from the virus and or have severely compromised immune systems. HCQ puts out the fire it doesn’t rebuild the house. Imagine a fire truck showing up at the start of a fire and saying, “lets wait until the roof collapses before we turn on the hoses”. Maybe its time to lock of doctors for criminal negligence for killing patients by not prescribing HCQ as soon as possible.

    7. Zeke says:

      The dose recommended for covid is the same as that used for rheumatoid arthritis so we have ample data to know the safety profile of that dose. And then there are the lupus patients that take a similar dose for extended periods of time (years).

      Despite the backlash, it is the most common drug being given for Covid worldwide so hopefully we will have good data. Might not work, but the safety profile is well established. It may not be HCQ but I suspect there is something progress being made with treatments that we will soon hear about. New York is still having plenty of new cases but the patients aren’t getting as sick. # intubations/day, need for ICU/ventilators for new patients is down

    8. Jim Heath says:

      The drug is tested, has no short term side effects, and has been shown to be very effective in every study done so far. Granted, those studies were limited in the number of participants, all of whom were very I’ll with Covid-19, and most importantly, all showed some improvement from the hydroxy therapy.
      Why is this being so avidly resisted? Is resistance the new normal.

      1. Dr. Guy Gordon says:

        “has been shown to be very effective in every study done so far.”

        Because this is not at all true.

    9. Scott says:

      if you are going to treat a disease with hcq, a known zinc ionophore, wouldn’t it be important to administer zinc as well?

    10. johnnygenlock says:

      Since the hydroxychloroquine is not readily available in Texas, and I hear it has preventive or inhibition effects on the COVID 19 when used in the proper cocktail, I have been substituting TONIC Water from Health Food Stores with no idea the Quinine content level. A friend, also attempting to self-medicate, claimed Quercetin has the same or similar effect of the Hydroxychloroquine in opening up the “channels” and making the Zinc Sulfate effective. When I went looking for any evidence the Quercetin helped, I found studies of its use in limiting the side-effects of Chloroquine; which I found interesting. So I wanted to pass that along for discussion while requesting a REPLY if anyone has input on whether Quercetin is in any way a viable substitute for HQ.

    11. Bryan says:

      The drug doesn’t work and Trump touting it was dangerous.

    12. Dar Wyn says:

      Your family is told you will not likely survive through the weekend alive and sadly succumb to SARS-Cov-2. It’s better to die without trying new treatments that worked on some people because brilliant egos believe the statistics do not support these treatments. We need to study them for a few years, at least 10 year study, so that in my next life, these can be statistical sound treatments approved by the statistical gods of medicine because they have 100% certainty in their extensive research to show these methods don’t work (yet!). Where would we be without these genius folks who were born with all the knowledge of the world.

    13. Trevor Marr says:

      Hydroxychloroquine combined with Zinc was found to help, not just straight Hydroxychloroquine. I question the intent of the WHO and UN and Left.

    14. Neal R Monda says:

      It seems a shame that we got off on such a wrong foot with azithromycin when doxycycline should have been used instead as it doesn’t compound the possible QT prolongation of hydroxychloroquine.
      Will you let us know if you think the best thing is a very short article that examines this rather than further speculation on how to conduct studies that have no benefit to the general public and shouldn’t be used even an emergency patients. You might address the absence of zinc or even zinc level testing in all the hydroxychloroquine studies which originally found that as an ionophore to zinc, chloroquine allowed zinc to more easily enter attacked cells where it is shown to interfere with viral replication as we have generally known for years.

      1. mario lento says:

        No Neal, you listed using two antibiotics which do nothing to a virus… they are used in case of secondary infection. If this is what you learned from reading this article or post, I understand. There is just a ton of misinformation here, or intellectual confusion and dishonesty.

        I chose not to take the azithromycin offered to me with my Covid 19 case and instead took Quercetin and Zn, and made sure to up vitamin D3. Quercetin in also a Zn ionophore like HCQ. 4 days later fever and cough broke and next day I was fine. I am 55. The reason for not taking the antibiotic was that I did not have a bacterial infection and I did not want to take it unless I actually needed it. Antibiotics have far more side effects than HCQ, but you won’t hear that unless you do the medical research.

        Forget about the nonsensical worry about QT elongation. Yes, that is a small potential, and especially if used for long periods of time, with people with documented heart problems. But that media spin is designed to make you stop thinking. HCQ is much safer than almost every drug you see advertised on TV!

        Why else would HCQ be used for more than half a century long term with almost no side effects for almost all people.

        Acetaminophen in overdose can seriously damage the liver. If the damage is severe, a liver transplant may be necessary in order to save someone’s life.

    15. mario lento says:

      To the author: I will try my best not to ever read any more drivel from you. Seems that you are only trying to prove you were right when it is abundantly clear that you are wrong. Anyone who makes the claims that a Zn ionophore and Zn does is not an incredibly smart treatment for early stages of Covid 19 or other RNA viruses, has no understanding of how to seek truth.

      This article and previous ones that miss the point I just made, while be looked at historically as part of the reason people died that didn’t need to.

      At best these articles can only make people less intelligent.

  2. Jesse N. says:


    I am not a doctor or even a healthcare practitioner. I have appreciated reading your blog though and it has certainly helped increase my understanding of things. I am wondering what your thoughts are on this study from Australia about the use of Invermectin:

    Thank you.

    1. philip says:

      This is in vitro but happy to hear your thoughts Derek.

      1. Paul says:

        For its approved use in treatment of onchocerciasis, Ivermectin is incredibly potent against the parasite. The human dose is very small (6-18 mg tablets) and it’s often only given once I think. Which is one of the reasons why it’s quite safe for humans. That gives a maximum concentration in plasma of about 60 nM.

        The paper that Jesse N cites has IC50s of about 2.5 uM. To get to that kind of concentration in humans you’ll need to massively increase the current dosage of Ivermectin which would require a lot more preliminary safety studies. I wouldn’t hold out much hope for it.
        Drugbank lists the LD50 of Ivermectin in rats at 10mg/kg so it’s pretty toxic (
        For comparison, Wikipedia lists sodium cyanide at 6.4 mg/kg for rat –

    2. MrRogers says:

      The IC50 for this effect is ~10x higher than the blood level achieved in any study published so far–even one that gave participants 10x the typical dose.

      1. Farva says:

        Have to look at tissue concentrations (lung especially in this case) not just plasma. Given the drug’s Vd it’s worth looking into.

  3. Tom Boyer says:

    Nice piece, thanks! I’m perfectly willing to believe studies that undercut the Marseille/Raoult assertions. But that Paris study has a smell of someone who had an agenda. Find 11 patients in your hospital who are the least likely to benefit, give it to them, declare the treatment a failure and Didier Raoult a fool!

    But meanwhile the death rates in France (except for the Marseille subregion) are atrocious and NOT declining. Deaths in Italy and Spain are plummeting — and the inflection point is EXACTLY when those governments, out of sheer desperation, authorized widespread use of Plaquenil at the end of March.

    So instead of fighting Roault, the brilliant minds in Paris had better figure out what is working in Marseille — and, for that matter, in Italy and Spain. Maybe it’s not chloroquine, maybe it’s something in the water. But the disparity in death rates is undeniable at this point. Something seems to be going on.

    1. a says:

      The onus is on you to show these slowing death rates on valid, statistically comparable curves. I’ve seen no such data.

    2. Paul says:

      Not sure where your information about Marseille is coming from, but it’s clearly incorrect. Here are the up-to-date graphs by region for hospitalisations and deaths. Marseille and the Bouches du Rhone department stand out as being one of the worst areas in the south of France!

      1. Tom Boyer says:

        Thanks very much for sending that link! Great data.

        Using the data on that page: Paris: 3075 hospitalized, 593 dead, works out to a 19% death rate. Recovered/dead 2.2.

        Bouches-du-Rhône (includes Marseilles), 1095 hospitalized, 96 dead, 8% death rate. Recovered/deceased is 7.8.

        I don’t know how they define hospitalized but I’m guessing this is admitted patients. The Marseille clinic treats a lot of outpatients so if they’re preventing people from needing hospitalization, that wouldn’t be accounted for in these figures.

        So basically, I don’t know what it means but If I got this disease I would rather be in Marseilles than Paris right now.

        Kind of like all those doctors out there saying, I know I should be waiting for randomized double blind peer reviewed studies from multiple sites around the world — but in the absence of that, I’m prescribing HCQ for myself and the people I love.

        1. a says:

          Prescribing is the key word here. If you’re prescribing when people are geniuinely sick, fine go for it.

          If you’re prescribing early, when 80-95% of them won’t need treatment, you’re conducting an uncontrolled clinical trial on people yourself, with an agent that has been shown (see above) to cause QT/Arrythmias, and likely other interactions with drugs including metformin. As well as wasting resources.

          Good luck with giving some of them a drug they don’t need, and, what was in that hippocratic oath again, oh yes, “causing harm”.

        2. Bernard says:

          The published update of the Raoult’s treatment are there:
          Tests on 1061 patients COVOD-19 positive.

          Until now
          Positives treated at the IHU 2397 10 deaths
          AT Marseille icluding IHU with the same protocol
          Treated: 3998 Deaths: 39

          1. loupgarous says:

            Case fatality rate of ~1% then, which isn’t a great improvement over the standard of care without CQ/HCQ.

    3. Rob says:

      If I read correctly, it said 11 consecutively admitted patients, which would suggest they said “with this person and the next 10 who are admitted, we are going to test this treatment”. That being said, 11 is fairly statistically insignificant (as are 40 and 80), and the whole point that was made in the preprint with 11 individuals is “broad clinical trials need to be carried out before recommending this treatment”

    4. MTK says:

      The inflection point is also about two weeks out from when both Italy and Spain put their entire countries on lockdown.

      Correlation doesn’t equal causation and in this case we have several correlations.

      I would say this much, HCQ with or without azithromycin may show some effectiveness, but it doesn’t look like the effect is going to be large. 72% of Spanish physicians surveyed said that they have prescribed it to their COVID-19 patients. The daily fatality rate for the last 7 days has been 11.4%. The overall fatality rate to date in Spain is 9.8%. I realize that this is simplistic since deaths lag behind new cases on any given day and completely non-scientific, but the point is if HCQ had anywhere near the 100% effectiveness that Raoult reported we probably should have seen some indication in lower fatality rates given the seemingly widespread use in Spain. We haven’t seen any sign of that all.

      I’m not saying it doesn’t work, just that if it ends up showing that it does, it’s probably going to be a moderate effect for some subset of patients. We’re still going to probably need other therapeutics.

    5. Guessed says:

      Sinister agenda? They are just doing exactly what every internet commenter is yammering for them to do: treat sick patients with HCQ/AZI!

      Then they do it, and report poor results.

      What an agenda.

      They should have kept it quiet so nobody would know; that IS the essence of science, is it not?

      Now, the HCQ believers will come along and say, “well, what did you expect, they were REALLY sick! And then they will say that there was no control group, so we don’t know how those patients would have done without the HCQ.

      The sad thing is that the French researcher COULD have done a proper, randomized controlled study a month ago so that we could have some confidence in its efficacy, or would have moved on to other candidates.

      At the end of this process, without studies we won’t know if this really helps, and we will have this argument every six months with each wave of coronavirus.

      1. loupgarous says:

        Googling, I had to look for a source not already outed as agenda-driven, and this came up from Reuters:

        “South Korea reports more recovered coronavirus patients testing positive again. SEOUL (Reuters) – South Korea reported on Monday that at least 116 people initially cleared of the new coronavirus had tested positive again, although officials suggested they would soon look at easing strict recommendations aimed at preventing new outbreaks. South Korea reported only 25 new cases overall on Monday, but the rise in “reactivated” patients has raised concerns as the country seeks to stamp out infections. Officials are still investigating the cause of the apparent relapses. But Jeong Eun-kyeong, director of the Korea Centers for Disease Control and Prevention (KCDC), has said the virus may have been reactivated rather than the patients being re-infected.”

        That last sentence is nightmare fuel: what if SARS_CoV2 acts like herpes simplex and flares up now and then? Is it still contagious when it flares up after supposedly being cleared from the body?

  4. Hap says:

    1) False hope is worse than no hope – giving people hopes without something worth hoping on is unhelpful.

    2) Maybe the question for an intervention should be “How do you tell if you have a parachute, a bedsheet, a piece of paper, or a Maltese Falcon?” That’s what trials are there for.

  5. Sanjay says:

    Honestly, this “bring people hope” crud is raised in the dumbest way; we recently had this argument with a sister-in-law who is an MD and was touting impossibly good studies with no knowledge of them, while I am an infectious disease scientist currently mobilized by the feds to help with this stuff. Absolutely, let’s bring people hope. But any power we have to do that comes from their understanding that we have training and professional mastery of what the science is and how it’s used and if you break from those things what you’re bringing isn’t hope. There’ s lots of reasons in the data to hope for better outcomes than the worst-case scenarios. We can push those, and encourage the behavior they demand, without going off into fairyland.

    1. loupgarous says:

      “Bring people hope” was the mantra of the people pushing Laetrile, various chelating agents and other ineffective “cures” for cancer back in the ’70s and ’80s. All too many times, it rhymed with “pick people’s pockets”, while crooning to really sick people that this stuff really, really works – when it doesn’t.

      Let’s get it right, in small words – No. you’re not bringing people hope. Hope for badly ill people is care proven to work. Now be quiet and let the grown-ups work.

  6. Jake O says:

    Nothing to add except a quick “thank you” for all the work you put into these updates! It’s good to have a consistent source of actual information. Stay safe out there!

  7. philip says:

    “My job as a researcher has not to been to raise people’s hopes without data in hand, my job has been to try to produce such data so as to raise hopes with some reason to do so.”

    error in the first statement?

  8. David Young MD says:

    Consider this. I speculate that the vast majority of people ill enough to be in the hospital with Covid19 are taking Hydroxychloroquine. I know that all of the inpatients at our local hospital are. I also know that there are millions of pills available now from the various manufacturers. Still, HydroxyC is difficult to obtain at the local pharmacy…. the stockpile of pills must be going to the hospitals, who would have first priority. I am making an argument that most people who have acquired Covid19 in the past three weeks are given Hydroxychloroquine and this will happen for the next three weeks as well. If Hydroxychloroquine works as well as Raoult says it does,…… then there should be a dramatic decrease in ICU admissions, a dramatic decrease in hospital length in stay and a measurable decrease in deaths. This hasn’t happened yet and if it doesn’t happen in the next week, then one would conclude that the benefit of HydroxyChloroquine, if present, is modest. Studies might show a small benefit and we all patiently await the results of the placebo controlled, randomized studies that should reach maturation soon.

    1. TNR says:

      Thank you for this response. My concern with the hype that is being given to this drug combination is if by giving it to everyone, we delay the results of the randomized trials of this drug and other drugs. Then we definitely have “something to lose” if it turns out that the clinical benefit is small for this drug combo but much larger for another drug – but we never find this out for 12 months because of enrollment difficulties.

    2. MTK says:

      oops. Basically posted the same thought above before reading your comment.

      Agree totally on your assessment given what’s known to date.

    3. Tom Boyer says:

      Very good point, if it really is being used a lot, it should show up in the numbers at the macro level. NY state deaths have leveled off, and given that cases were skyrocketing 2 weeks ago, that is being taken as a good sign by some. Does HCQ have anything to do with it? Cuomo was very guarded but said something to the effect that anecdotal reports are positive.

      Unfortunately we really don’t have any stats on the extent to which HCQ is being used in NY, other than people seem to think it’s a lot. We do know the major hospitals are trying to recruit patients into studies where only half of them will get real treatment. To the extent that chloroquine is available outside of the studies, I bet it makes recruiting volunteers kind of interesting: “You might get no treatment and die, but hey … science!”

      1. Sam says:

        No way in hell I would consent to a placebo controlled trial, If I’m on a vent. Give me HCQ+AZ+zinc.

    4. marelyn eve shapiro says:

      You say it is given to ot in the hospital so why would there be a dramatic drop in admission?

    5. Robert Leithiser, Ph.D. says:

      Not true. Most people getting the drug are near end of life, being intubated. If you want to see where it is be using routinely, look at India, Malaysia, Bahrain, Saudi Arabia, South Korea, Poland where the death rates are like 20 – 100X less than even the US. Italy, Spain, France are using it, but just started within the last 2 weeks doing it beyond giving it to people that were mostly already dead.

      1. David Smith says:

        U.S. – 4.0% reported deaths as % of reported cases
        India – 3.4%
        Poland – 3.5%
        Malaysia – 1.6%
        Saudi Arabia – 1.3%
        Bahrain – 0.5%
        South Korea – 2.1%

        A big unknown is how COVID-19 deaths are attributed – the above might be apples vs oranges comparisons. A virus-positive person might die from heart failure – is that due to virus or heart disease?

        In any case, death reduction is not 20X and the exact impact is unknown until possible data collection differences are resolved.

    6. mario lento says:

      You’re post seems sensible, but you cannot make such a claim without quantification. HCQ and Zn should “prevent” people from going to hospitals. People who get sick enough to go to hospital ate 10 or more times as likely to die based on the data. You should understand this! That you don’t should give you pause.

      The data today!
      83,366 deaths
      1,408,039 total cases
      Mortality rate: 5.92%

      There’s the data

      Now we know that the actual mortality rate is at least 10, maybe 15 times lower than that. How do we know? Because we can test the general population and realize that the people not counted in the actual number of cases are the ones that are not skewed because they were largely taken at hospitals.

      Follow me.

      Since no intelligent person thinks or states that HCQ + Zn kills the virus. Instead it stops the RNA replication, it is far less effective once you need hospitalization. It needs to be used to PREVENT hospitalization.

      So people you are seeing are in a skewed distribution of people who are already 15 x as likely to die and many have started on their cytokine storms and other complications, where the drug combination is not claimed to be effective!

      The only studies that are of value, are ones ran where people care understanding the facts, and use it as early as possible (if the treatment is warranted). This makes it inconvenient to do double blind studies since the people not receiving the drug will not fare as well. These doctors care more about life than about proving something they already know.

      Do a little thinking instead of this political ranting nonsense.

  9. PTI says:

    Pardon the interruption, but according to the Con artist-in-chief, this question has been answered at least “15 times”. Here’s how we make informed decisions in the U.S. now:

    1. Suzanne says:

      It was recently reported that Pres Trump and family’s trust has investments in a company that makes a generic version of chloroquine. I think it’s called Sinapro or similar. I didn’t pay attention to details of company or name at the time.

      1. therealestg9 says:

        It’s Sanofi, a very large pharmaceutical company which has thousands of investors from around the globe. And it’s stupid to push the conspiracy theory that Trump is pushing the hydroxychloroquine just so he can make money from it. Now I don’t know the financial details of Sanofi, but I believe this is a generic drug which is available for less than $1 per tablet, the company’s stock price is not going to be shooting up just because there is a demand for hydroxychloroquine. Since it’s generic, there are going to be plenty of other companies making it too.

        1. Betsy A Riley says:

          google the stock price of sanofi–it recently had a 28% jump.

          1. therealestg9 says:

            Lol. Yes, because due to the coronavirus and the combined stock market crash, people are investing in biomedical and pharmaceutical companies. Sanofi does not have a patent on this anymore. Numerous generic companies have been manufacturing this for decades, and selling it for very cheap prices (less than $1 per pill). There is a huge amount of disinformation being circulated right now, from all sides of the political spectrum. The narrative that Trump is somehow going to benefit significantly from pushing chloroquine is yet another example. It also indicates that people who believe this don’t know much about the workings of the pharmaceutical industry.

        2. JayR says:

          Seriously. This has to stop. Including Trump’s financial interest in any comment undermines the credibility of the rest of any comment. Snopes has investigated whether Trump has a financial interest and has rated it mostly false. Yes, Trump has an interest in one or two of 12 or 13 generic manufacturers in a family trust managed by JP Morgan by means of a mutual fund, but the value of that interest is insignificant. Snopes, not a known Trumpster site, stated Trump’s personal interest in companies that produce HCQ (“an unprofitable generic drug”) is virtually negligible. He probably has no idea the stocks are in these mutual funds. Do you know all the stocks in any mutual funds you own. Sadly, the NY Times is harming its credibility publishing this drivel and seemly has succumbed to Tabloid clickbait.

      2. mario lento says:

        Yes. One of the funds is a mutual fund, (I assume you know what that is) and one of those funds may have increased on order of several hundred dollars in value because it is associated with something related to one of these inexpensive drugs I do not know if it is HCQ and Chloroquine.

        It’s supposed to make people think Trump was pushing something to enrich himself.

        What else would you expect from left news sites that say “true” things, but are meant to mislead? They make wonderful hateful and misleading quotes to be argued about by less intelligent people.

    2. Maxie says:

      Its going to be another rough day for you when all the eggheads and experts are proven wrong and the rabble rousing populist is proven right as they roll this out across the globe and people start recovering.

      1. Anonymous says:

        The experts are saying we need more data and that there is only a suggestion so far of efficacy. Only strawman experts or nonexperts say it has no effect as of now. It’s a hypothesis that HCQ works and nothing more. It might work. It might not work.

        1. Philip McDunnough says:

          The middle of a crisis is hardly the time to be messing around with randomized control based studies. We don’t of course know if HCQ+ antibiotic+zinc works or not. The toxicity issue is one thing. It would appear that this really is not a problem. I am not someone who would know. I simple listened to the interview of Dr Daniel Wallace by Dr Oz. Dr Wallace is someone who should know, so I am willing to believe that HCQ for 5 days or so is safe. The vision issue seems to be a non issue unless, this is taken for years. The aspect that bothers me a bit is the combination with the antibiotic which may increase the heart risk issue. I have no idea. Hopefully just HCQ+ zinc would have zero risk. That would be nice to know.

          Many here seem to want a randomized controlled study before this is allowed to be attempted. I understand the desire to have replication, as well as a standard form of measurement between experiments ( which would rule out the Bayesian input mentioned earlier). I am curious, and honestly don’t know, if the social distancing approach that most people are willing to accept has ever been subjected to the same degree of analysis. Does anyone know? Quarantines have been used for a long time. They seem to work, but are really crude, desperate treatments. In the current case, has the limited quarantine lowered net fatalities, and will that still be the case when the poverty, and other issues, caused by all the shutdowns be factored in? Perhaps a different type of limited quarantine would have been better ( separating old from younger, for example)? I don’t know and I wonder where the randomized control studies are for what has been a really harsh treatment applied to most of the world.

          Finally, I view replication as an important component of science. It is a powerful tool for building up a pyramid of knowledge with strong pieces. I am not convinced that it can be achieved in all softer science related fields. The statistical inference issues are not obvious, the use and interpretation of p values really puzzling and the use of randomness questionable. The placebo inclusion is one I have difficulty with, but I fully understand the desire to measure changes in variables.

          We all strive to get closer to truth. How to do that is complicated. After around 40 years of being a research professor of statistics ( but now retired to the level of layman) I must tell you that I am deep misgivings about much of the subject and its growth to areas where it seems to be of dubious value.

          The lack of personal control, and the increasing power being assigned to experts, is discouraging. It is a time where one feels like a lab rat controlled by nameless people of unknown abilities and motives.

          Best to all…

    3. Trebitch says:

      On the advice of Dr. Fauci – claiming millions of potential deaths – ten million already lost their jobs, most will never work again. I understand, that they are not your people, rednecks, waiters, minimum wage guys and girls. They don’t know the secret handshake, the key to the club, the key words of “orange man bad”. They probably even voted for him, so they deserve it.
      However, some of you may look at the actual CDC statistics, here:
      There is no epidemics. No pandemics. The total weekly death rate in the country has no sign of increasing (in fact down to 40000 per week from the normal 53000 per week, probably due to no driving) and even the total pneumonia/flu death rates are within normal or even lower than normal!
      Nobody even took notice of the 2017 flu season, with twice the weekly death rates and much higher total death rates than now!
      The hysterical moronic imbecility now in evidence far surpasses the dishonest times of my youth in formerly communist Hungary. Hope you will enjoy the world you are building. Maybe your job is so important and you are so intelligent, that you won’t have to join your despised countrymen now standing in the unemployment line, although I would not be so sure, if things don’t change in a few days.
      Sorry for the rant. I am old and just realized that I am of no help to anyone in this brave new world, where neighbor snitching on neighbor taking a walk is the height of virtue and encouraged and praised by the Powers That Be. (details, not mine, here:

      1. Abacus says:

        Trebitch, every year 5 to 20% of the US population gets the flu. Currently 0.1% have tested positive for Covid 19. Each infected covid patient infects approx 2 to 2.2 other people (R0 or r-nought). Influenza patients will infect around 1 to 1.2 other people. Consider that the mortality rate from Covid is around 30X greater than the flu. If 5% of Americans contract Covid you could expect over a half million fatalities. If measures are not taken to curb the spread, a 5% infection rate would be beyond optimism. Should we let it run its course?

        1. Trebitch says:

          No country, not even Italy, shows any excess deaths. In fact, total death rates are still below the 2017 flu season death rates everywhere.
          Most coronavirus death cases are essentially reclassifications from flu/pneumonia death. Your estimates of possible death rates from coronavirus are insane. Wuhan is opening up. Korea is open.
          If there would not be tests for coronavirus nobody would have noticed any strange happenings, it would have been just a bad flu season again, just as in 2017.
          Fugit impius, nemine persequente; justus autem, quasi leo confidens, absque terrore erit!

          1. Trebitch says:

            I am replying here to myself, as Derek below just states that I am wrong with no reply to button, so here it goes:
            Mr. Ciro Montagano in the linked article uses the data tables from the Italian Statistics site:
            From these very tables the total death rates for Lombardy region for the month of March from 2015 to 2020 are:
            2015 2016 2017 2018 2019 2020
            8552 8037 8059 8523 8543 8587
            I don’t quite see the reason to panic.
            The paper referred to by Derek does some hoky stuff, concerning Lombardy, but it does NOT make sense!

          2. Abacus says:

            Trebitch, I think you are missing the point. The estimates are based on not doing anything and going about our lives like nothing has changed. These “low rates” are the result of the extreme measures to contain it. Did the world enter “Lock Down” during the 2017 Flu season? At this point barely any of the population has Covid (560,000 in the US currently). During the best flu year 16.5 million Americans will get it. During the worst over 60M.

      2. Stephen says:

        you obviously don’t understand the concept of exponential growth

        1. Trebitch says:

          Evolution of all epidemics follow the logistic curve. Nothing in nature is exponential, except in a very limited range. The logistic curve can be approximated by the exponential only for about halfway to the inflection point, it becomes approximately linear between the 25% and 75% points, and is saturating above.
          Fugit impius, nemine persequente; justus autem, quasi leo confidens, absque terrore erit.

        2. Trebitch says:

          I am replying to Derek, here, as there is no reply button under his note to me.

          Perusing the italian gentleman’s data, from


          The total mortality rates in the entire Lombardy region for the full month of March for the years 2015-2020 are:
          8552 8037 8059 8523 8543 8587
          Maybe my italian is not as good as my latin, but I fail to see any reason to panic.

      3. Bernd Meyer says:

        The current US Covid-19 death rate is 1,000 to 2,000 deaths per day. And that’s *confirmed* deaths. Actual death rate is definitely higher, possibly by a fair amount.

        Typical traffic death rate is 100 deaths per day. Typical flu death rate is similar to that, up to about 300 deaths/day during a really bad season.

  10. ENES says:

    Keep up the good work Derek although no need to refer more folks to Dr. Oz, lesser the better. I liked the discussion on effect size and was wondering if in a future (topic appropriate) post if you can discuss in some detail NNT – numbers needed to treat. I find myself explaining this concept to folks more often these days and most if not all seem to understand this quite intuitively. My 2 cents…

  11. Alia says:

    And you’re doing a great job, Derek. Thank you.

  12. KwadGuy says:

    You write: “One more point: someone last night was trying to tell me that my job was to “bring people hope” and that my attitude wasn’t helping with that task.”

    No, Derek…Your job is to be an articulate, critical and clear voice in a time of rampant paranoia, unfounded optimism, and unfounded pessimism.

    As such, I think your columns have been admirably on point.

    Keep on doing…

    1. TNR says:

      +1. Although I took Derek’s comment as sarcasm in response to you know who.

    2. Jeff Bennion says:

      I’m one of the people Derek refers to, but he was misunderstanding me. He is claiming I said he needs to give people hope. I didn’t say that. I said he misunderstands what Trump is doing by boosting all the possible treatments that are out there. Trump and Fauci have different roles, and Lowe is in a similar position as Fauci, but not as public. It is not mutually exclusive for a national leader to be hopeful and positive in reassuring a population that is tramautized, afraid, and looking for hope, and then for the scientists to be cold-eyed and strict in looking at what actual data does. Both have their place, and both are important. Where we get into trouble is when scientists think they know leadership better than leaders or when leaders think they know the science better than the scientists. They both have their place, they are both important.

  13. Andrew Molitor says:

    I confess that I am baffled by what we’re seeing.

    Why even bother with these ridiculously underpowered studies? 11 patients? How is this anything except wasted effort, there seems to be literally no way you can learn anything at all from this study.

    What could possibly motivate anyone to perform this study?

    1. G2 says:

      It a yet another publication of the authors for their CV, although the first autor can not even write his name two times the same 😉

    2. Guessed says:

      It is a hot topic and everyone who has some experience treating patients knows that they can get crap like this published and put a notch on their CV.

  14. therealestg9 says:

    Why does no study look at combining chloroquine with zinc? The first time I heard about chloroquine was from a MedCram Youtube video which talked about the results of this paper:

    ( “Chloroquine Is a Zinc Ionophore” by Xue et al. (2014).

    Zinc is known to inhibit replication of RNA viruses:
    Source: Te Velthuis, et al, 2010. Zn2+ inhibits coronavirus and arterivirus RNA polymerase activity in vitro and zinc ionophores block the replication of these viruses in cell culture. PLoS pathogens, 6(11).

    According to this theory, the chloroquine helps to facilitate zinc transport into the cell where it can inhibit the RNA dependent RNA polymerase which is characteristic of these types of viruses. It just baffles me why zinc supplementation is not being tested in combination with the chloroquine derivatives and azithromycin. It’s at least worth trying right?

    1. Rosie says:

      I think some Dr’s are doing that. I’ve been on some blogs and some Dr’s and nurses are saying that its as if the patients are so sick that the treatment of Plaquenil does nothing to help them.

      Its brutal and sad.

      I’m a fan of them trying an IL-6 inhibitor after I read they used it on critically ill patients in China. It would make more sense to use that on cases that are too far ahead. Dr’s say that these people are dying of cytokine storms which IL-6 inhibitors could help.

      There are some trials and I hope if its working Dr’s talk to each other. This is about life and death and yes if its helping they need to get the word out just like they have on plaquenil and z packs. it wouldnt be fair to patients to have to wait and see the outcome of trials.

      1. JP Leonard says:
        I posted about zinc here yesterday and again today regarding Dr Zelenko’s claim about 100% cure Z paks (HCQ+Azithromycin+zinc). I ask why not try to replicate his results.
        I mention established work on the online NIH library showing how essential zinc is to the immune system, and how zinc deficiency is linked to old age and the chronic conditions typical of severe Coronavirus cases, as well as to complications from pneumonia.
        Also regarding drawbacks of HCQ, another zinc ionophore is Quercetin, which also has been studied as an antiviral agent. e.g. Quercetin as an Antiviral Agent Inhibits Influenza A Virus (IAV) Entry.
        Regarding ethical problems of larger trials, I’ve suggested a trial on patients with less severe symptoms, where half the patients get HCQ and half get the placebo for the first 3 days, then they switch places, and you compare their charts and see if they did better on the HCQ days. Or you could give quercetin plus zinc instead of placebo. In fact, it might be wise to give almost everybody zinc supplementation, I saw somewhere on NIH that it even helps when your serum zinc level is normal.

        1. Anon the II says:

          I’ve been associates with a large number of high-throughput assays over the years. Quercetin and analogs show up a lot. So much so, that we tend to avoid putting them in libraries just to avoid having to explain why they aren’t worth following up. Just saying. Again.

      2. Foster Robert says:

        Agreed….. I believe if there is any efficacy to using HCQ, it is earlier in the cycle. In the later stages and the rate of viral growth, HCQ doesn’t have a significant amount of binding sites remaining. Although, I’m not sure what blood oxygen levels correlate to unattached Viral impacted hemeglobin. So it’s not kinetics, but percentages. It would be interesting to understand the viral loading compared to non impacted hemeglobin at EOL

    2. Smut Clyde says:

      Why does no study look at combining chloroquine with chocolate pudding?

      1. Ken says:

        Or colloidal silver? I remember a scientific study – well, it was an ad by a disgraced preacher selling the stuff, but close enough – that said it was a 100% cure for covid. Also cancer, measles, and male pattern baldness.

      2. Farva says:

        Hey Smut Clyde! What’s good man! Would you be interested in co-authorship on a paper I’m working on? Similar to Rajeshkumar et al. I am going to administer CQ or metformin at doses known to be lethal in mice, but I’m going to combine each with chocolate pudding. When the mice die, I am going to suggest that the combination of chocolate pudding with CQ or metformin is lethal to mice and has the potential for a drug interaction. Cool huh?

      3. Alpheus says:

        To be fair, the person who suggests linking zinc to HCQ actually gave a good theoretical basis for why it might just work. What theoretical basis do you have to try HCQ with chocolate pudding?

        1. chiz says:

          Mood and psychological factors can contribute to health outcomes. Since chocolate pudding can contribute positively to mood its plausible that it could contribute to health outcomes. Anecdotally I know that when I have a cold, sometimes caused by coronaviruses, that I often feel better haven eaten some. Plus, puddings will contain trace quantities of zinc.

          1. therealestg9 says:

            Please state, without the annoying sarcasm, whatever disagreements you have with the numerous studies that have shown zinc’s ability to inhibit viral RNA-dependent RNA polymerase, and thus act to slow down the replication of these types of viruses. Have you personally done blood tests on a large group of coronavirus patients to determine if they have the adequate levels of zinc in their system (which would disprove my hypothesis). It is well documented that diabetes and other disorders can lower zinc serum levels. Could this not be a contributing factor to these patients’ susceptibility to the virus?

          2. Alpheus says:

            The theory you present for why chocolate pudding might be relevant for treating COVID-19 is still not as convincing as the case that zinc might help.

            Indeed, I would even say that the case you just gives highlights just how unfair and ridiculous it is to mock the idea that zinc might just help, and should be seriously considered.

      4. Nick says:

        Hey! I had that idea first!

    3. Truth9834 says:

      LA doctor seeing success with hydroxychloroquine to treat COVID-19

      Summary – he states that it works but only if used in conjunction with Zinc, in that hydroxychloroquine by itself did not help. He states that his patients get dramatically better within 8-12 hours!

  15. Lawrence S. Mayer, MD, PhD says:


    Are you aware of the facebook page

    It is 1700 clinicians and epidemiologists reviewing and discussing the latest in epidemiology and related sciences for frontline critical care docs. Over 1000 are physicians. We post your opinions and would love for you to join us.

    1. Derek Lowe says:

      I’ve heard of that one! Unfortunately, I deleted my Facebook account a couple of years back. . .

    2. JP Leonard says:

      I’m aware of the Covidnerds group and wanted to join, but after I heard that they delete posts about zinc – maybe even as an antiviral prophylactic, which is widely-accepted mainstream science – I figured I’m better off here.
      At least Derek lets me post, even if he doesn’t seem too excited about HCQ+zinc therapy. But I wouldn’t mind joining that group if they let me, just to see what I might learn there, even without posting.

      The rationale is they are too busy now with dying patients on their hands. But how long does it take a doctor to add zinc to a patient’s regimen? Less than it takes to read this post?
      Dr Cardillo says his patients are symptom-free in 8 to 12 hours with HCQ+zinc. How much time could be saved by curing patients so quickly?
      The Sermo survey showed only 15% of clinics were giving zinc or Vitamin D, while 46% were using HCQ. Anybody who is immune-challenged has good reason to take both those minerals. They are cheap and readily available. Why not give zinc and Vit D a try.
      I couldn’t find what dosage Dr Cardillo is giving, but Jeremy Scott here on the Comparing HCQ Trials thread gave these figures
      “Dr. Zelenko lists his treatment regimen as follows:
      – HQC, 200mg, 2x a day for 5 days
      – AZ, 500mg, 1x per day for 5 days
      – Zinc, 220mg, 1x per day for 5 days”

    3. Glenda Parkman says: I would be very interested to know what the group of physicians/scientists you represent think of the article accessible through the link I’m providing. My niece, an ER nurse of many years and now a Nurse Practitioner, was asking her medical colleagues about it.

      1. quinoline mensch says:

        It is an interesting alternate Covid disease mechanism hypothesis which fits with the 4-amino quinoline (HCQ/CQ/amodiaquine etc.) class’s main antimalarial mechanism/site of action (stabilizing heme in red blood cells (RBCs) against attack by plasmodia)

        There is a nice clear YT yesterday from Chris Martenson (PhD. Pathology) covering this new hypothesis (starts at minute 21:20) :

        An important unresolved question with this hypothesis Chris clearly points out is that it does not explain how the proposed heme-disrupting ncov proteins would be able to get inside of the RBCs in the first place.
        Human RBCs lack a nucleus, therefore supposedly also lack the cytoplasmic and nuclear machinery needed for translation (synthesis of) the viral proteins that, according to the hypothesis, attack/degrade the 1-beta chain of hemoglobin. and release toxic iron Fe+2/+3 species massively into the local environment, to trigger a cascade of downstream inflammatory damage, for this proposed mechanism.

        Who knows though? Immature RBCs are nucleated, and it may be unknown I suppose whether enough vestigial replicase activity and translation machinery remains in RBCs after maturation for the invading ncov virions to hijack and utilize to replicate themselves.

        1. Bannem says:

          A very quick search online tells me that new RBCs enter the circulation as reticulocytes, which while enucleated, contain ribosomal RNA, and can still synthesise hemoglobin. This suggests to me that there still remains sufficient protein manufacturing ability within the reticulocytes for the virions to utilise. Furthermore, reticulocytes destroyed by SARS-Cov2 virions will not mature into erythrocytes, reducing the oxygen carrying capacity of the blood . . .

          1. quinoline mensch says:

            Further intriguing bits connect this “ncov virus attack RBC hemoglobin” hypothesis that fit with observations of the beneficial effects of  zinc ions (Zn+2) in the HCQ cocktail tx regimens:

            According to this mechanism,  the ncov  ORF proteins  (separate/distinct proteins from the viral spike protein) attack hemoglobin and breaks  the Fe+2/+3 iron coordinating heme core away from its protective globulin “nest”  that allows the hemoglobin complex to bind  and carry oxgygen molecules ( O2 ) reversibly.  Strip away this globulin coat and the iron-heme core becomes exposed to a more aqueous  intracellular milieu,  where it becomes bathed  with aqueous reductive cofactors (NADH, NADPH, FMNH2 (?) etc) PLUS  the O2.  

            Under these new conditions the iron-heme complexes become tiny  free radical  factories to crank out lots of reactive oxygen species like the  superoxide radical anion (O2.-),  which ccorrode almost every cytochemical molecule and macromolecule they touch.

            The ultimate results being  a cascading inflammatory response.

            And what are the cytosolic (water soluble) protective enzymes  present  inside red blood cells whose function is to soak up and neutralize these  free radicals?
            Why it is ZINC /Copper superoxide dismutase  (ZnCuSOD), originally known as erythrocuprein or hemocuprein.


            So there is another interesting link that ties together Covid disease course/tx observations  with a rationale that accounts for 4-aminoquinoline antimalarial /Zn regimens’  mechanism of action lying at the RBC-hemoglobin level.

            (2nd Attempt to post this)

        2. quinoline mensch says:

          Further intriguing bits connect this “ncov virus attack RBC hemoglobin” hypothesis that fit with observations of the beneficial effects of zinc ions (Zn+2) in the HCQ cocktail tx regimens:

          According to this mechanism, the ncov ORF proteins (separate/distinct proteins from the viral spike protein) attack hemoglobin and breaks the Fe+2/+3 iron coordinating heme core away from its protective globulin “nest” that allows the hemoglobin complex to bind and carry oxgygen molecules ( O2 ) reversibly. Strip away this globulin coat and the iron-heme core becomes exposed to a more aqueous intracellular milieu, where it becomes bathed with aqueous reductive cofactors (NADH, NADPH, FMNH2 (?) etc) PLUS the O2.

          Under these new conditions the iron-heme complexes become tiny free radical factories to crank out lots of reactive oxygen species like the superoxide radical anion (O2.-), which ccorrode almost every cytochemical molecule and macromolecule they touch.

          The ultimate results being a cascading inflammatory response.

          And what are the cytosolic (water soluble) protective enzymes present inside red blood cells whose function is to soak up and neutralize these free radicals?
          Why it is ZINC /Copper superoxide dismutase (ZnCuSOD), originally known as erythrocuprein or hemocuprein.

          Sohere is another interesting link that ties together Covid disease course/tx observations with a rationale that accounts for 4-aminoquinoline antimalarial /Zn regimens’ mechanism of action lying at the RBC-hemoglobin level.

        3. therealestg9 says:

          This hypothesis was posted in another comment, and I’m copying my response to it here again:

          I have done graduate work in bioinorganic chemistry, and I am speaking from that experience.

          Two things about this:
          1) I strongly disagree that iron is being pulled out of the porphyrin ring of the heme protein. These hemes are used as catalytically active sites in numerous enzymes in our bodies, encountering a range of chemical environments various types of chemical environments. There is no way that a simple, relatively unreactive glycoprotein from a virus is going to be able to dislodge the iron. Heme proteins are way, way too robust for that, otherwise they wouldn’t have been found in so many of our enzymes.

          2) I believe the author is on the right track when he mentions zinc. Do a ctrl+F search on this page for “zinc”. There have been a lot of links and information posted on this page about zinc and its combined effects with chloroquine to provide antiviral activity.

          1. Derek Lowe says:

            Agreed on the idea of pulling iron out of heme – that’s not an easy process, and it’s not something that the virus has selection pressure on it to do.

          2. quinoline mensch says:

            I would share your view that for the major toxic effects to occur by this ‘covid attack on hemoglobin’ disease hypothesis, the hydrophilic (water-loving) the stiil-coordinated iron-heme cores would remain intact after being clipped out by the viral ORF proteins, away from their hydrophobic globulin coats.

            Clinical observations from a frontline Doc:



          3. JP Leonard says:

            Just read the chemrxiv article Josh referred to and found this interesting: “chloroquine could prevent orf1ab, ORF3a, and ORF10 [Covid proteins] to attack the heme to form the porphyrin, and inhibit the binding of ORF8 and surface glycoproteins to porphyrins to a certain extent, effectively relieve the symptoms of respiratory distress.”
            The mechanism of attacking hemoglobin to suffocate the patient is pretty scary.

      2. Derek Lowe says:

        I am still thinking about the hemoglobin-binding idea in this – opinions coming soon. But the author makes a number of mistakes that I have noticed so far (the coronavirus has no DNA in it, malaria parasites are not bacteria, there are indeed many reports of unilateral ground-glass opacities, and more).

      3. Brad Baillod says:

        Can anyone provide a few fact checks for me (just a concerned not-yet-COVID+ layman):
        * Do COVID patients with low oxygen levels show elevated hemoglobin?
        * Is elevated hemoglobin also seen in non-COVID pneumonia ARDS patients (i.e. is it present in any low-oxygen condition)?
        * I’ve heard there are a few unilateral cases, but what percent of the time is COVID lung opacity bilateral? What percent of time is non-COVID pneumonia ARDS bilateral?
        * Is it possible to detect high levels of iron ions in COVID patients? Do they also appear in non-COVID pneumonia ARDS patients?
        * Is it possible to distinguish between alanine aminotransferase caused by damage from iron ions as opposed to damage from oxygen deprivation? Do non-COVID pneumonia ARDS patients show high levels of that enzyme?
        * Is viral replication within the red blood cell a necessary condition for this theory to hold? Is it impossible for virus particles originating elsewhere to affect red blood cells in large numbers?
        * If ventilator pressure may be doing more harm than good, do the studies going on with HCQ control for ventilator pressure?

  16. Tucker Goodrich says:

    Metformin and HCQ, in humans:

    “This double-blind study randomized 267 uncontrolled type 2 diabetes patients (HbA1c ≥7.5% and ≤11.5%), post 3 months’ treatment with glimepiride/gliclazide and metformin, to additionally receive hydroxychloroquine 400 mg/day…”

    “…well tolerated.”

    1. Thomas Dahlgren says:

      Yeah, people with poorly controlled diabetes rarely develop hypoglycemia, a known side effect of HCQ.

      I’d like to see the results of a study where HCQ was added to the drug regimen of people with well controlled diabetes.

      Not sure the participants would want it though.

  17. Diego Fleitas says:

    Come on! You have teared your clothes with the 30 and 80 cases (non random) studies from France, and another from China, and you now lightly quote a study with 12 cases, which only lacks somebody crashed by a truck!
    The other analysis and your comments are more interesting, but perhaps the “anecdotal evidence” is just noise. We don’t know it.

  18. charlie says:

    On the endpoint issue:

    Look I see that viral load is a surrogate endpoint; we don’t know what it really means for treatment.

    But the patient centers endpoints are pretty arbitrary as well. ICU stays maybe a bit less so, but how long they spend in the hospital is.

    If you can reduce the viral load to near zero in Day 6-7 by a drug, that alone is worth it as those people will not be infectious. You can move to other beds. You don’t need to use forty pounds of plastic PPE for staff. You can send them home and not start new chains of infections.

    IN terms of patient endpoints, reducing the severity of the fluid in the lungs would seem to be the strongest and you could really ignore those patients.

  19. The Metformin + Hydroxychloroquine data that you mentioned came from exposing mice to a
    crazy high dose of each!! For a 100 Kg human, these would amount to 6000 mg per day of hydroxychloroquine and 25,000 mg per day of Metformin.

    1. ab says:

      Um, no. Please look up allometric scaling. A useful reference is J. Basic Clin. Pharm., 2016, 27-31. In short, you’re off by at least a factor of 10. Mg/Kg does not scale linearly with body weight between mouse and human.

  20. heteromeles says:

    I’m not in health care or biomedicine. A quick google of “hydroxychloroquine metformin” led me to the Prescriber’s Digital Reference and this page:

    The list of drug interactions with serious consequences (severe hypoglycemia, Q-T prolongation, and decrease of seizure threshold) is rather eye openingly long, and I identified a bunch of drugs (many variations on the theme of metformin among them) that are very widely used that may have serious negative interactions.

    Out of a slight abundance of caution, I would strongly urge people like myself (who can google just enough to be really dangerous), to NOT take hydroxychloroquine as prophylaxis against Covid19. Staying home and being anti-social is cheaper and safer.

    Presumably experts working in an actual hospital or clinical setting can read this and figure out appropriate responses, tests, and workarounds. Hopefully they’ve got enough time to actually check for drug interactions before they start administering hydroxychloroquine, too.

  21. cynical1 says:

    I think chloroquine and hydroxychloroquine are probably a red herring at this juncture.

    With that said, you have posted what appeared to be some positive clinical data on the use of favipiravir which targets RNA-dependent RNA polymerase and is approved in Japan for use against a number of RNA viruses. The big hope everyone seems to have now is remdesivir which targets the same enzyme. Realistically, it seems more likely that favipiravir could be brought on-line faster.

    You wrote on a previous post about favipiravir: “Mechanistically I have trouble seeing how it can, though, and have since the beginning of this whole epidemic, since it barely does anything in the in vitro assays.”

    For those of us without access to search engines or the literature, can you elaborate on what in vitro assays you are referencing? Ones against the polymerase or some antiviral effect against coronaviruses in a cell line? No activity against the polymerase might worry me but it does seem to have broad effects against a lot of RNA viruses and is approved for them in Japan. Can you elaborate on the “mechanistically” part?

    1. Derek Lowe says:

      62 micromolar in a cell assay of viral replication (remdesivir was much better, FWIW).

      1. cynical1 says:

        So there is nothing mechanistic about that assay in any sense?

        Could you put into context how well in vitro Vero cell line antiviral efficacy typically translates into in vivo efficacy with RNA viruses in that reference in any species? Or for any virus? And why would you believe that the in vitro efficacy in a kidney epithelial cell line derived from an African green monkey should automatically translate into in vivo efficacy with coronaviruses? Especially given that the reference you provided were comparing antivirals with widely disparate antiviral MOA or basically no realistic MOA (ie. chloroquine? Nitazoxanide?) for use against a coronavirus. And 0.7 uM with Remdesivir isn’t making me feel any better either. How did it work against Ebola in Vero cells for which it did not work in the trials best I can ascertain?

        It is important to put into context how well in vitro antiviral activities translate to in vivo efficacy in both animal models and humans across the board. I am not trying to be difficult but based on 20 years in the area, I roll my eyes about an awful lot of in vitro antiviral effects I observed and read in the literature. (And definitely your citation.) But, admittedly, I never worked on a coronaviruses either.

        After everything I read on your blog and elsewhere (albeit without literature access), I’ll put my money on favipiravir……….but precious little money.

      2. OC says:

        From that study:

        “However, favipiravir has been shown to be 100% effective in protecting mice against Ebola virus challenge, although its EC50 value in Vero E6 cells was as high as 67 μM, suggesting further in vivo studies are recommended to evaluate this antiviral nucleoside.”

        Could Favipiravir have some additional invivo mechanism that isn’t well understood?

        Frankly of all the studies that have been released (yes I know controls were Kaletra and Arbidol, disease was mild, they are pre-prints, not peer reviewed etc.) the two Favipiravir studies out of China are by far the most hopeful. Am not writing off Remdesivir but frankly NO studies have been released yet, the treatment has to be given intravenously and the ability to ramp up production is likely to be a very time consuming affair.

  22. Tom Boyer says:

    American Thoracic Society has just released paper “suggesting” chloroquine for hospitalized patients with a COVID-19 diagnosis and evidence of pneumonia. Citing paucity of evidence but saying they reached this conclusion after discussions with doctors around the world treating these cases.

    Is this the dam breaking? And how bad will the drug shortages be and soon can enough supply be manufactured?

    1. John says:

      This is causing a shortage for people who rely on hydroxychloriquine (Plaquenil) for lupus and RA. I have lupus, and have relied on plaquenil for years. Now, most pharmacies are simply out of the drug (that includes CVS which falsely told the press they would maintain a supply for existing lupus patients). Even my health insurance company now limits the number of pills it will cover – 22 pills in 90 days. That hardly helps when I need 2 a day. I finally found a pharmacy and had to pay 12 times what I paid just a couple of months ago.

  23. Tom Boyer says:

    Italy, Spain, France deaths plotted on a graph. Italy officially authorized widespread use of plaquenil on March 28. Spain was about the same time but I don’t have the exact date.

  24. Ronald Kluger says:

    According to the latest from the FDA, genuine placebos, such as a shot of B12, will provide their well-established positive results – and there are no side effects . I’m sure that some political leaders will then support giving them to everyone, whether or not they are showing symptoms. Most will recover and do better than a control group. Some will do worse than the control group.

  25. Walter Li says:

    Report this morning about a doctor in LA who saw benefits on his serious ill patients using HCQ + Zinc.

    1. Dirk Johnson says:


      Maybe because news outlets are more interested in embarrassing Trump than in reporting news?

      Good god,what have we come to where news editors are more interested in seeing people die than in giving Trump a talking point?

    2. JP Leonard says:

      This doctor says he found HCQ only works if combined with zinc.
      It’s what I was saying earlier – maybe the trials of HCQ are so spotty because it only works on patients that have enough serum zinc to transport into the cells.
      “Sunday, April 5, 2020 8:48PM
      LOS ANGELES — A Los Angeles doctor said he is seeing significant success in prescribing the malaria drug hydroxychloroquine in combination with zinc to treat patients with severe symptoms of COVID-19…
      Dr. Anthony Cardillo said he has seen very promising results when prescribing hydroxychloroquine in combination with zinc for the most severely-ill COVID-19 patients.
      “Every patient I’ve prescribed it to has been very, very ill and within 8 to 12 hours, they were basically symptom-free,” Cardillo told Eyewitness News. “So clinically I am seeing a resolution.”
      He said he has found it only works if combined with zinc. The drug, he said, opens a channel for the zinc to enter the cell and block virus replication.
      He added that the drug should not be prescribed for those who are presenting only mild symptoms, as there are concerns about shortages for patients with other conditions who need to take the drug on a regular basis.

      Thank you Walter Li, and ABCNews too

      1. JP Leonard says:

        More Zinc Links (as promised)
        especially related to heart problems and hypertension which are the most risky comorbidities with Covid16. Prevalence of Zinc Deficiency in Cardiac Surgery Patients.
        “Of 56 patients 53% (n=30) had abnormally low plasma zinc levels (<12μmol/L… zinc deficiency is common in cardiac surgery patients, especially in the presence of hypertension, hypercholesterolaemia or obesity."

        The Relationship between Serum Zinc Level and Heart Failure: A Meta-Analysis
        "there is a significant association between low serum zinc levels and heart failure."

        Zinc deficiency is an independent risk factor for prehypertension in healthy subjects.

        Dietary zinc intake is inversely associated with systolic blood pressure in young obese women
        "results suggest that zinc deficiency is an independent risk factor of an elevated blood pressure"

        Zinc deficiency induces hypertension by promoting renal Na+ reabsorption.
        "Zn2+ deficiency (ZnD) is a common comorbidity of many chronic diseases" –
        (That's what we wanted to know – because chronic diseases predict for death from coronavirus)

        Zinc in Infection and Inflammation
        "Zinc plays an intricate function during an immune response and its homeostasis is critical for sustaining proper immune function."

        Zinc as a Gatekeeper of Immune Function
        "the adequate function of virtually all immune cells is highly zinc-dependent."

        In one of these NIH articles I saw a mention that zinc assists the functioning of other antiviral treatments. That's exactly what we're seeing now with Zinc+HCQ.

        And yeah, there might be a little zinc in chocolate pudding. The most common cause is reduced dietary intake.

        1. therealestg9 says:

          Thank you so much for these links. Yes I’m a bit biased because I had to learn a lot about bioinorganic chemistry as part of my graduate work. I think the biggest issue is academic arrogance. Something along the lines of “oh it’s just a natural mineral, surely the solution can’t be that simple or we would have thought of it already”. Zinc is one of the most interesting minerals because it is a cofactor for so many enzymes and does so much to keep our bodies functioning properly, especially in the immune system and also numerous other DNA/RNA interactions. But I would be willing to bet that many people are not eating complete diets and are thus getting minor levels of zinc deficiency. Another fact that I’ve read (but haven’t been able to substantiate) is that men who engage in frequent masturbation or sexual activity are also at risk of getting zinc deficiency. Something about how the prostate stores >75% of our body’s total zinc ions. But anyway, here’s hoping that more people start becoming aware of zinc.

    3. K Christiansen says:

      My Boss’s son lives in New York and he contracted the virus. I know that he was given Hydroxychloroquine and Zinc. I’m not sure what type of Zinc and I can’t recall if he was also given Azithromycin, but there was a quick improvement in his symptoms. If I’m not mistaken I thought I was told he has asthma as well, either way..thankfully he’s recovered.

  26. ScientistSailor says:

    What is the effect size of a parachute on falls from a 1st floor window? 2nd? 3rd? etc. That’s how I would answer that comment, no?

  27. Thomas Clarke says:

    While I agree that the original Marseille study is so poor as to be essentially useless, and studies so far have shown mixed results for HCQ treatment of COVID, this RCT gives me grounds for some guarded optimism especially when combined with plausible biochemical reasons for a positive effect:

    It is only a preprint, but a relatively high quality trial, although on only 31+31 patients.

    Surprisingly it is not that often cited in comment on HCQ when of all the published data it looks to me like the most directly informative to the uses now being suggested. Big caveat – it is a small trial.

    1. Jesse C says:

      I can’t disagree strongly enough about the quality of the trial. The groups were clearly unbalanced at baseline; without a sufficiently randomized sample you simply can’t draw conclusions with a frequentist approach to the statistics.

    2. quinoline mensch says:

      Replying to Thomas Clarke

      Also I’ve never seen any of Dr. Zelenko’s (upstate NY) first person HCQ tx informative explanatory YT’s on HCQ topic presented from this blog.

      Here is a recent one:

      (Attention hovering Bot-flies: No making fun of the beard. The Doc’s an orthodox Jew)

  28. Stephen says:

    Alinia (nitazoxanide) has shown inhibition of Sars2 in vitro. I was previously effective against Sars1 and Mers. It is also known to block IL6. Losartan *might* block the ability of the virus to bind to ATR recptors on cells.

  29. Dennis says:

    Frankly, I find this HCQ discussion ridiculous. So many people are only talking about this only because Trump pushed it. This is the only reason!!!
    There are plenty of evidence in vitro that HCQ may be effective against SARS-COV2 and there are several potential mechanisms how it can do it: pH effects, posttranslational modification of ACE2 etc. Do the Pubmed search and read the papers. HCQ also showed up in several known drug screens to inhibit coronavirus replication in cell culture. These screens had some additional interesting candidates. Also, HCQ is a drug with a well-known safety profile. It has side-effects no doubts about that. But in terms of known toxicities no other drug in the running comes close including remdesivir. It is also cheap to make and if effective it can provide a realistic way to help control COVID19 around the globe. I think testing it is justified while doing a risk/benefit analysis for each patient. Also it is important to analyze COVID19 stats for patients already taking HCQ. How many lupus patients on HQC get COVID19 vs what is expected? Finally, I doubt that HCQ will be effective in controlling fully blown COVID19 disease. Perhaps it will be effective only when taken earlier during disease progression. This has to be taken into account. So, I personally hope people stop discussing this drug and let doctors analyze its effects properly. HCQ has nothing to do with Trump.

    1. Stephen says:

      It is risky to suppress the immune system. Hydroxychloroquine has a half life of 50 days, meaning it resides in the body for nearly a full year. If you react poorly to it, you are screwed.

      1. chemist says:

        that’s not how it works.

  30. Drug Developer says:

    1. CQ and HCQ: these are getting used interchangeably a little too often, which seems wrong.
    2. The working assumption seems to be that HCQ is “better” for this disease than CQ. Is that a good assumption (assuming that either might work)?
    3. I understand the urgency to just find something that works, but I haven’t seen any dose-response clinical work underway or proposed. For a variety of reasons discussed above this could be important information, even if it takes a little while to obtain.

  31. Michael Kinder says:

    I am the founder of Kinder Scientific, which made a number of GLP level pre-clinical measurement devices for toxicology.

    Great information Derek!
    Would I take the drug(s) if I were on my death bed? Maybe.
    Would I ask that it be broadly used without sound science behind it? Not in a chance.
    Misleading people does not give them hope, it gives them a false sense of hope, which is a very different thing.

  32. Freon Sandoz says:

    Very good article, but where does the 0.1% estimate for mortality of seasonal flu come from? I think the estimates that I’ve seen (e.g. are 0.02% or lower, which means that Covid-19 is at least 50 times as deadly. Am I reading the seasonal flu mortality estimates wrong?

    1. Stephen says:

      Percentage of patients that die who tested positive.

      1. OC says:

        If that is the measure then it is self evidently NOT the true case fatality rate then is it?

        Almost ALL influenza fatalities will be captured in the numerator given a patient who is going to die of influenza is very, very likely to be hospitalised for complication prior to death and tested for the virus.

        On the other hand there are huge numbers of flu patients who recover at home after having never been tested (or even going to see a Doctor).

  33. Gareth Wilson says:

    “One more point: someone last night was trying to tell me that my job was to “bring people hope” and that my attitude wasn’t helping with that task.”

    Stephen Colbert asked Ta-Nehisi Coates something similar once, and was told to talk to his pastor.

    1. Druid says:

      I would talk to my pasta if I could find any

  34. Brovid-69 says:

    Have any commenters here had COVID yet?

  35. anon says:

    Who is financially benefiting from all the prescription of HCQ? When in doubt, follow the money.

  36. Dan Wilson says:

    Do you have any thoughts on this paper that says that Covid-19 should possibly be treated the same way as High Altitude Pulmonary Edema using acetazolamide, nifedipine and phosphodiesterase Inhibitors because the pathophysiology of Covid-19 is very similar to HAPE

    1. OC says:

      I’m surprised at the lack of impetus behind getting a clinical trial done for these drugs in patients whose ARDS is presenting more like HAPE than classical viral induced ARDS (i.e. high compliance, low recruitability).

      It would seem like a pretty obvious candidate for a randomised clinical trial to assess the benefits these drugs may have:

      1) Randomisatiom occurs at the point in time where clinicians would normally intubate a patient on oxygen therapy.

      2) Control patients would be intubated as normal.

      3) Active arm patients would continue on oxygen therapy and be given acetazolamide.

      4) Primary endpoints would be survival at 3, 7, 14 and 28 days. Improvement in oxygen saturation could be tracked continuously also.

      Given somethongmlike 2/3rdsnor more of intunated patients are dying would seem like a worthwhile trial. These drugs are cheap and are given in the outpatient setting normally so should be relatively safe in the ICU environment.

      E.g. Findings from northern Italy suggests patients ARE NOT presenting with typical ARDS (at least prior to intubation) but with an issue around effective diffusion and vasoconstriction of the alveoli.

  37. Ed Ostrin says:

    A basic fallacy is that somehow suppressing an immune response in ARDS will somehow avoid the worst of it. We’ve had decades of experience with steroids in ARDS and the effect is modest if any. Many other anti-inflammatories also have weak or mixed support as well (plasmapheresis, antioxidiants, NSAIDs, etc). In fact, a profound initial inflammatory response, mediated through those same TLRs that HCQ inhibits, may be preventative. Trials of numerous TLR agonists are underway and several have shown promise.

    There is likely tight interplay between innate immunity provided by the respiratory epithelium, cell mediated immunity against virus-infected cells, death of those cells, and secondary inflammation from the denuded respiratory tract and alveoli balanced with late suppression by Tregs and other repressive cells. This balance is subject to countless host and environmental factors. For instance, if early viral clearance is associated with profound airway damage by cytotoxic T lymphocytes, followed by profound danger signals or secondary inflammation, maybe it could be counterproductive…

    Like always, we will need to wait for the science to see what HCQ is actually doing. I’ll cross my fingers that anything will work. But I definitely think we need to proceed with caution.

  38. Rtah100 says:

    Chloroquine is available over the counter in the UK. Going somewhere malarial and not resistant, here’s a week/month’s worth. Yes there’s a long list of contraindications but seriously, you wouldn’t roll the dice. The odds of CQ killing you are a lot lower than C19 and if it doesn’t do anything at least you didn’t catch malaria! 🙂

  39. Farva says:

    And there are already studies in humans taking metformin and HCQ; I stopped after the first few pages of results but there are a lot of abstracts and papers where the two are combined in humans without adverse effect:

    Chandra AK, Ahsan S, Ranjan P, Sinha AK, Kumar RR. Efficacy of Hydroxychloroquine as an Add on Drug with Basal Insulin, Gliclazide and Metformin in Subjects with Uncontrolled Type 2 Diabetes Mellitus. International Journal of Diabetes and Endocrinology. 2019 Jan 7;3(4):58.

    Baidya A, Pattanaik SR, Shankar A. Efficacy and Safety of Hydroxychloroquine as an Add-On Therapy in Indian Patients with Type 2 Diabetes Mellitus Inadequately Controlled With Two Oral Drug Combination and Basal Insulin: A 72 Week Observational Trial. International Journal of Research and Review. 2019;6(11):218-24.


    1. Farva says:

      This study used flawed allometric scaling with body surface area and administered lethal doses of each compound to the mice. This had nothing to do with any supposed drug interaction. The LD50 for metformin in mice via ip administration is 247 mg/kg (they gave them 250 mg/kg) and for CQ it is 66 mg/kg (they gave them 60 mg/kg). It shouldn’t come as a surprise that these mice died. This is a terrible design flaw. These doses are not equivalent to the therapeutic doses that humans use.

      1. Zephir says:

        And guess what? Just few months before coronavirus outbreak hydroxychloroquine did show excellent results just for prophylaxis of diabetes – actually much better than many super-duper modern (and expensive) drugs, like canagliflozin from SGLT2 group of antidiabetics. So I wouldn’t definitely take hydroxychloroquine interaction with metformin way too seriously.

      2. Jennifer Herman says:

        I was about to make this same comment. They appear to have given oral dose via intraperitoneal injection (which has much lower LD50). There might be some synergy between HCQ/CQ and metformin (both lowering blood sugar) but simple explanation is that mice died because of the inappropriate dosing. Moreover, there are no documented contradictions for using these medicines simultaneously in humans. At least some would be expected if there was deadly drug interaction.

  40. Pedantic Speaker says:

    “Ah, but the effect size of having a parachute at 10,000 feet is very, very large. And the larger the effect size, the smaller a trial can be and still have meaning.”

    With an effect size *that* large, you don’t even *need* a control group.

  41. JP Leonard says:

    Well, seems to me like the reports by Dr. Zelenko in NY and Dr. Castillo in LA – 100% cure with HCQ plus zinc – are in the parachute class of “With an effect size *that* large, you don’t even *need* a control group” – if it works it works!

  42. David B says:

    Note that “anecdotal” in the Bayesian context means “positive but weak” not “anecdotal” in the ordinary sense of the word. As I understand it, evidence that has a BF of over 1 but under 3, is referred to as anecdotal, but that includes evidence, as in this reanalysis, of a BF of 2.6, which means over a doubling of the odds of a difference from the Bayesian prior (I think).

    1. Chatfield says:

      and why did they need to introduce a Bayesian prior to “reanalyze”what is claimed to be a statistically significant result? The significance tester is free to do her reanalysis of the Bayesian result, and thereby find the result significant.

  43. Dr Aust says:

    I suppose there could be one silver lining. With all this crazy hoo-ha about chloroquine/ hydroxychloroquine, the trials of other candidate drugs like remdesivir and the Japanese antiviral might be able to get done properly, since no-one will be yelling about them as ‘miracle cures’.

  44. ex-Glaxoid says:

    Has anyone simply looked at blood zinc levels verses degree of sickness from CV19? I seem to remember that lower zinc levels are common in diabetes, and mutations in zinc dependant proteins are amoung those that are found in type 2 diabetes, so maybe low zinc or intracellular zinc has some effect on CV19 seriousness. Just a thought.

    I certainly would be willing to try HCQ and AZ along with zinc, in controlled or not trials, if I was sick and thought it might have any effect. While it clearly is not a miracle drug, it can’t hurt to test it, as long as normal care if used. i’m guessing that most doctors are going to watch for side effects and contraindications, although they are clearely overwhlemed in some places.

    Lastly, has anyone written about EIDD-2801? It looks easy to make, compared to Gilead’s drug, something even I could make in the lab in a week, and is also going into trials soon. It, along with favipiravir (in between the two in cokplexity) look much simper to scale up quickly and has some limited in-vivo data that looks good. Not that ease of synthesis is that important, but in a crisis, I would prefer something that can be made in bulk quickly.

    1. A Nonny Mouse says:

      Favipiravir is a pain to make; black and brown crud everywhere…… Costs a fortune to clean the bessels… Although now off patent and should be open for all, the purification via a DCHA salt is heavily patented.

  45. Bob says:

    With the parachute analogy, his many broken ankles/bones would it take for the parachute to be considered to have a dangerous enough side effect for it not to proceed to wide usage? How many would say that money is better invested in better planes as opposed to parachutes?

  46. Pedantic Speaker says:

    “Well, seems to me like the reports by Dr. Zelenko in NY and Dr. Cardillo in LA – 100% cure with HCQ plus zinc – are in the parachute class of “With an effect size *that* large, you don’t even *need* a control group” – if it works it works!”
    With a parachute at 10000 feet, the effect size is “you’ll survive just about every time, assuming you know how to use the parachute and it was prepared properly” (I remember an NCIS episode involving a defective parachute) vs “you’ll definitely die”.
    There *are* some medical situations in which the effect size is almost this stark; I remember in Ben Goldacre’s book, Bad Pharma, in which he uses (IIRC) antibiotic treatment of Mycobacterium tuberculosis-caused encephalitis (a complication of tuberculosis) as an example of a situation in which such an effect size is relevant: If they cure even one or two people, you know that they work.
    However, even when the treatment is highly effective, he noted that ordinary tuberculosis (ie, Mycobacterium tuberculosis infection of the lungs) was *not* such a case, even when it universally went untreated because the antibiotics needed hadn’t yet been invented. In fact, he described how the first modern clinical trial was run by the NHS to find out whether this new antibiotic worked against tuberculosis; they used the fact that the government had Britain’s only supply of the drug as leverage to enroll them in a trial to see whether the drug even worked (sort of like what New York is planning with HCQ against COVID-19).
    In this case, even assuming you and ABC7news are communicating the study correctly, the effect size is approximately “100% cured” for HCQ+Zn versus “99% recovered anyway 1% died” for the general patient population; you *do* need a control group for an effect size of this order of magnitude, simply to prevent the result from being distorted by recruitment bias; also, the study has to be large, to account for the fact that the adverse effect you’re measuring is so rare; this is one reason why a practical study is going to require more common endpoints (like Lowe, I’m not a medical professional, but I’d suggest
    “complications requiring intensive care/assisted ventilation” and “days in ICU/on AV” as an absolute minimum, even without knowing of hospital capacity issues and lack of ventilators).
    Also, no discounting patients who die, like *some* COVID trials I’ve heard of.

    1. Ed says:

      100% cured within 8 to 10 hours, vs 99 percent recovered within 2 weeks and one death. That’s my understanding of what is being claimed.

  47. Gary Cornell says:

    Given what is in the Hopkins preprint cited in this post. if you are on Metformin you would have to be pretty stupid to take HCL. Even if the effect is off by a factor of 10 in humans as opposed to mice, HCL would be a pretty deadly drug for all the people taking what is, after all, the fourth most prescribed drug in the United States.

  48. Gus says:

    Here is a review of the HCL and ZN combo.

    1. Gus says:

      Based on this one, it seems taking OTC Quercetin and high-quality ZN would be beneficial.

  49. Professor and Chair John Cooper says:

    Mayo clinic prescribes hydroxychloroquine for patients with QTc<470 and exhibiting severe respiratory illness associated with Covid-19 as long as delta QTc remains below 60 after treatment to prevent side effects (ventricular arrhythmias).

  50. Herbert Jacobi says:

    I would say it was how bad I had it. If it was just chills\fever, aches etc. Sort of like the regular flu but worse I would say no. If it got to the point where I had to go on a ventilator and had problems breathing I’d change my mind.

  51. Carl Pham says:

    I think sometimes these issues have an unfortunate aspect of things seen versus things unseen. We see the people with the disease right now, and think — how can we not do everything possible for them? To hell with the careful data collecting, just throw whatever looks like it’ll float to the drowning man. If it doesn’t work, oh well, but if it does — we’ll have done something good. There’s no downside to trying.

    But what this perspective does not take into account is the many more people who are unseen — those who will come down with the disease in the future. By throwing away the insistence of doing careful measurement now, we delay, or even derail entirely, the development of knowledge that will help them. When they get sick, unless we have use our present time wisely, doing the solid research that gets us reliable answers, then we will be in no better position than we are with the people who are sick now. We’ll again have to just throw everything in and hope something floats.

    If the people currently sick were all that would ever get sick, then it would be reasonable to go with desperation measures. But that’s not the case. The odds are good that there are many more people who will get sick in the future than are sick right now. It may be hard on the people who are sick right now, but if we throw away science we do much greater harm, because we betray all those people in the future who are going to get sick.

    1. OC says:

      I would vehemently disagree with you that those who are in favour of treatment without waiting around for readouts from conclusive randomised double blind studies are ignoring those yet to contract the disease.

      The fact is evidence from the UK suggests 50% of those who go into the ICU due to COVID-19 are dying.

      If in fact HCQ treatment does reduce the incidence of disease progression (and those requiring admission to the ICU) then continuing to only give supportive treatment is dramatically increasing the risk of ICU beds / ventilators being insufficient to meet the peak of the patient flow. In effect those surplus patients who cannot be treated in the ICU have been consigned to near certain death.

      Additionally if HCQ does clear the virus faster than supportive care alone then it should help reduce the incidence of infection of health care workers treating those who have been hospitalised but not admitted to ICU thus further reducing the risk of future mortality.

      On the other hand if in a couple of days / weeks we receive strong evidence of the effectiveness of other therapies (e.g. remdesivir) there is nothing that stops treating clinicians from shifting to the new therapy (in the highly unlikely event that Gillead has anywhere near the volume of the drug to treat the caseload that is).

      Further if HCQ becomes a widely prescribed treatment there is nothing that stops new potential anti-virals from being tested as the active arm in a randomised double blind clinical trial while HCQ is used as the control arm. Similarly there is nothing that would prevent those patients who haven’t responded to initial HCQ treatment being involved in clinical trials of treatments to treat cytokine storm etc.

      Finally while HCQ undoubtedly has side effects these are fairly well understood after decades and decades of use. Obviously clinicians should be screening patients for contraindications but the fact the drugs have been sold over the counter for decades as a prophylactic in many jurisdictions suggests the concerns here are vastly overstated.

      At the end of the day the decision should be left in the hands of the treating clinician (NOT the hospital administrator) and the patient (or patient’s family).

  52. Guessed says:

    People often criticize my skepticism about HCQ by saying it would be unethical to do a controlled study since we “know” it works; and what is the harm?

    If you look at drug labels for products licensed in the last 20 years or so, there will be a list of adverse events/side effects according to their frequency and severity, broken down by body system. So, you might find that Wonder Drug from 2012 has a 3% chance of causing neutropenia, a 1.2% chance of causing diarrhea, etc, etc.

    If you look at the label for drugs like hydroxychloroquine, you will not find that information in any detail. It may say that it can cause arrhythmias, or should not be used in pregnant women, is contraindicated in patients with macular degeneration, or prolonged QT intervals. It may also point out that it is contraindicated in G6PD deficiency, a variant enzyme that is common in the general population.

    But there will not be data that you can use to formulate an analysis of risk; it is said that these drugs have been around a long time and are well tolerated (true, and true), but you won’t find the risk of serious harm in patients in the label for the drug.

    Now, we are in an epidemic where people want to believe something works, and it has become a political litmus test for some, instead of a medical question. And they say that if you propose a controlled trial you have to attend the funerals of the patients who die in the control group because…we know it is safe and we know it works.

    So, if we conclude that it is unethical to withhold this drug because we know it is “safe” and it works, do the proponents of its use have to attend the funerals of patients who get fatal arrhythmias, or hemolytic anemia from oxidant stress? Do they say this should be used in children, who are known to have fatal overdoses with relatively small amounts of the drug, and whose chances of dying with this virus are extremely small?

    And the things that make the virus more deadly (advanced age, diabetes, renal failure, heart disease) are also the things that can make the drug more dangerous (elderly diabetic with heart disease and mild renal failure, on metformin; not an uncommon situation).

    There are likely some poor unfortunates who have cadged plaquenil prescriptions from their doctors and are taking it as prophylaxis, even though they don’t even have coronavirus. Wait until stories of deaths from fish tank cleaner is replaced with deaths from the worried well taking prescription plaquenil. It bet it will happen, if it has not already.

    The contraindications to this drug suggest a perfectly acceptable (if slightly flawed) clinical trial design. Compare outcomes of 1000 patients given HCQ to that of 1000 patients at the same (hopefully wide array of) institutions, same time, getting standard care, without HCQ due to G6PD deficiency, long QTc interval, pregnancy, renal failure. We are accumulating coronavirus cases at the rate of 8000 per day in NY, alone, and 30,000 per day in the US, overall. This study should not take long to perform, and would be a valuable performance. If only the true believers would be bound to honor the results. The true believers should be asked to specify what clinical trial outcome would convince them that the drug does not work, and show their math.

    There are also ways of conducting a clinical trial with continuous assessment of outcomes (adaptive trial design). You could conduct controlled trials of HCQ in asymptomatic infected patients, in mild (outpatient) disease, or early severe disease, all with the option of either the HCQ or control group getting “salvage” with open label HCQ, which would score the current recommended dose regimen as a failure in the event of disease progression, leading to a test of longer dosing, or scoring better outcomes in the treatment arm as a reason to halt the trial early.

    For my part, I am open to the idea that HCQ may be effective in some subset of coronavirus patients, possibly according to age, severity of disease, or strain of virus. But please show it before the next wave hits this fall.

    1. Guessed says:

      Edit to withdraw the comment on HCQ causing hemolysis in G6PD deficiency. There is literature that it does not cause hemolysis, unlike other quinine drugs.

    2. Zeke says:

      The arguments against using are valid in theory but moot for the most part because HCQ is being given in high numbers throughout the world to treat Covid, including in the US. While clinical improvement can be subjective, QT prolongation leading to arrhythmias is pretty black and white and we have seen no reports of any cardiac arrests from this medication from any country during this epidemic. This doesn’t mean its not happening, but does mean that it isn’t happening to an extent noticeable by prescribing physicians.

  53. Guessed says:

    Bingo. The other unseen is that all the bona fide advances in medical science have come to fruition with hypothesis testing, possibly after some hunch or lucky guess; it doesn’t matter.

    If we toss rational inquiry out the window because we feel like something must be right, we will wallow in the equivalent of laetrile based on testimonials or appeals to authority (credulous credentialism). And there will be no more advances except by random happenstance.

    1. chemist says:

      We are in “there’s a big problem to be solved ASAP” mode. If you find something that works, then go with it.

  54. Steve Hubbard says:

    Cuomo said today that that NY doctors say hydroxychloroquine results look promising based on use in NY hospitals. There are also results from Dr Stephen Smith, Dr Anthony Cardillo and Dr Zelensky and a couple more. When you have no other option, this appears to be the best bet. Why are so many people against it? What other options do Doctors have that have shown results. I’m all for trying other things but so far HCL seems to have shown more positive results than anything else. China also did a study on it that was promising. Have you heard of anyone dying from HCL?

  55. Guessed says:

    Not common, but it can happen. It will happen more if we start giving it to millions of people as some kind of prophylaxis or treatment of mild/asymptomatic disease.
    FDA:“Children are especially sensitive to the 4-aminoquinoline compounds. A number of
    fatalities have been reported following the accidental ingestion of chloroquine, sometimes in
    relatively small doses (0.75 g or 1 g in one 3-year-old child). Patients should be strongly warned
    to keep these drugs out of the reach of children.”

  56. JP Leonard says:

    Italy Starts Mass Treatment with Hydroxychloroquine
    They didn’t think about zinc, though

  57. MJ Lott says:

    Leronlimab from CytoDyn Inc. Small biotech, huge drug! Research it and you will come away impressed with it’s efficacy against COVID-19.

  58. Derek Freyberg says:

    This is getting worse than penny-stock pushing!
    Let’s leave it to those who actually know what they’re talking about (in which group I include our gracious host).

  59. George Lastrapes says:

    I worry that persons suffering the flu or the heebie-jeebies, but not tested for covid-19, will badger MDs into prescribing hydroxyquinoline, get over the flu or whatever, and be unalterably convinced that HQ saved their lives, and say so on ‘Fox and Friends’.
    Enough people do this and a conspiracy theory is born. Dr. Fauci is replaced with Deepak Chopra. Millions die. But those who invested in the makers of HQ are wondering how to spend their billions.

  60. Marz says:

    We lack double-blind research with big enough groups, but we can’t wait for such.

    So not with some diabetes medicines and only exactly when tiredness, shortness of breath, deep muscle a/o joint pain starts?

    Can we differentiate the differences within the several researches, to maybe get more clues, when potentially effective and when not?

  61. Robert Clark says:

    I read that article in Swedish about the stopped trials due to side effects on

    I was surprised near the end it said they used “chloroquine phosphate”. If this is what they really used that is surprising since it is well known that hydroxychloroquine has fewer side effects. The article also notes the doctors suspect he was given an overdosage.

    Sometimes the terms “chloroquine” and ”hydroxychloroquine” are used interchangeably, but it would be important to find out here which one was used. Also, what was that dosage the doctors suspect might have been an overdosage?

    Robert Clark

    1. The Truth is Hard. says:

      The chloroquine phosphate was recommended and written in the 6th treatment guidelines of covid-19 by the communist China’s government. This disinformation given by the Chinese communist party is totally a disaster.

  62. The Truth is Hard. says:

    Are you sure your update 2 is about Hydroxychloroquine or chloroquine? I suspect how many commenters know the different aspects of these two medicines.

  63. Robert Clark says:

    On the question of whether HCQ is protective based on a claimed lack of lupus COVID-19 patients, this should be something easy to give a yes or no to, so why isn’t this being done nationwide? Obviously, when a COVID-19 patient is admitted their health history is taken, so it should be the easiest thing in the world to report on whether lupus patients appear in that group.

    At about the 6:30 point in this video interview Dr. Oz discusses that lupus patients aren’t seen among COVID-19 patients and asks for people who know of cases to contact him:

    Robert Clark

  64. TLSL says:

    I’m not a physician or a scientist. I’m a lupus patient taking Hydroxychloroquine and I pray it is a successful treatment for people. I just wonder why I don’t see more talk about trying to find out if there are lupus patients who are on Plaquenil that are getting COVID-19. Seems relatively simple to me to set up a system to track patients taking Hydroxychloroquine and see if they are in the states that have been hit hard and succumbing to the virus.

    1. Alan Goldhammer says:

      The OHDSI group that works on combing for observational medical data in large datasets is looking at lupus and RA patients that are on hydroxychloroquine for treatment and whether there is a protective effect against SARS-CoV-2.

      1. stephanie wright says:

        Excellent. That is exactly what I hoped someone was doing.
        There are many people – including me – who have been taking hydroxuchloroquine for a number of years for autoimmune conditions, and would like to know this. Some do have other risk factors, but there is a substantial pool of people who don’t.
        It would be good to know if it reduces risk of infection, and if it changes the chance of serious illness.

      2. Robert Clark says:

        Thanks for that reference to the OHDSI group, Note this idea of combing the data across many different patients could be used for all medications not just HCQ. And it should.

        The question in this case is do the classes of lupus patients and COVID-19 patients overlap, like with Venn diagrams? Or are they distinct classes?

        Note even if there is an overlap this could still be useful. For instance, there are about 400,000 COVID-19 cases in the U.S. now. Lupus occurs at about 1/200 people in the U.S. So statistically we might expect 2,000 or so lupus patients among the COVID-19 patients. But, hypothetically, suppose it was only 200, or 1/10th the expected amount. Then HCQ could still be 90% effective at protecting against COVID-19, a very important result.

        I don’t get why it is taking so long to find the answer to that if they have the data available. Clearly, it’s an important thing to find out since we would have a million cases to base our statistical conclusions on, not just a few dozen.

        Robert Clark

  65. Sam C. says:

    It really amazes me to read through these comments and observe how inflexible the minds of many medical ‘experts’ seem to be.. these are not normal times and you need to temporarily throw out some old protocols.

    We are literally in the middle of a rampant pandemic, where our response time is critical to fighting back against a virus that has a fatality rate between 1-4% of those infected, with 100% of the population susceptible to infection.

    Yes, many of the drug combinations being tested will not work, and yes sadly some people may even die. But ultimately the net benefit of finding a cure is more than worth the risk, particularly when it involves the use of existing drugs.

    Or in your great wisdom should we instead wait 3 months or so for a proper peer reviewed cure to be published, and another 6 months to test for unknown side effects, whilst in the mean time millions of people die around the globe?

    1. JP Leonard says:

      Side effects from zinc? 🙂
      What we have here is more likely a latent epidemic of zinc deficiency that was actuated by a virus.
      Chronic conditions related to zinc deficiency, that became acute and fatal when this virus struck.
      A good immune system is our best health insurance.

  66. JL says:

    I cannot understand how HCQ can be given for decades casually on a regular basis as a prophylactic for possible malaria infection for travelers after a doctors screening. But for a pneumonia inflicted COVID patient who may be headed for a cliff it’s just Oh so terrible a choice, and especially for those who have entered the 1 in 3 ICU lottery. It’s been said that Einstein’s approach was to imagine riding a light beam. I think it’s time everyone consider what it’s like to ride gurney into the ICU, and not for a GD mosquito bite. And the Math alone should bring you there. If it’s safe for even 90 percent of the population, which I round down here just to make the math easier for the illogically impared, then that makes the 30% chance of leaving the ICU, if the possibility that HCQ does work for 9 out of 10, turn a corner to a 9 out of 10 chance. And if you can’t understand that quick math, you shouldn’t be in this discussion. WTF, get off your high “data” horse and ride the Fn Math gurney.

    1. Bannem says:

      The problem with HCQ is that one of it’s side-effects is QT prolongation, which can lead to fatal cardiac arrythmias. Now read this :-

      posted previously on ths Blog, especially the parts I’ve pulled out below . . .

      “Thus far many are dying of cardiac arrest rather than inability to ventilate/oxygenate . . .
      Then over 12hrs, newly cold, clamped, multiple-pressor shock that looks cardiogenic, EF 10% or less, then either VT [ventricular tachycardia, rapid heartbeat] progressing to VF [ventricular fibrillation, heart quivering or beating erratically] progressing to death, OR, PEA [Pulseless Electrical Activity, got a waveform on ECG–or EKG for you German-loving chemists–but no pulse felt in the body] progressing to asystole [flatline ECG] in less than a day. Needless to say this is awful for families who had started to have hope.”

      So yeah, let’s treat an infection whose major cause of death is cardiac arrest, with a drug that can cause cardiac arrest . . .

      1. JL says:

        In the real world where COVID-19 is the authoritay and not you, 60% or more of those intubated don’t come out alive. Apply some Math.

  67. JL says:

    Also, BTW, another disappointment I keep encountering with all those that claim they need more research is the lack of their familiarity with all the research and data that is already out there, the lack of immersion in the topic to really speak about it. If they were following closely, even taking one day out to do a deep dive on HCQ and what the mechanism of action may be, the tests everyone would be pushing for would involve the use if zinc. It’s admirable that there are many doctors prescribing HCQ and antibiotics to get results from that have been the core of the protocol in South Korea (bet many of the “researchers” detracting from HCQ did not even know that), but it shows that they have failed to include zinc which is what the in vitro research about HCQ has been about. When are you going to think out of your comfy box and really truly dig in on finding Everything you can find before pushing your keys. Lives are depending on it. Get out of your box when searching for answers. If you don’t know how to do that maybe you’d best stop telling everyone the same old tired “that’s the way it’s always been done” story, because you’re boring people to death.

    1. ToXDoX says:

      At no point in the Chinese in vitro study (which is what set off Dr. Raoult’s study and interest in HCQ) do they mention zinc. Your deep dive must be putting a toe into the kiddy pool.

      Don’t you people have chem trails to follow or report?

      1. JL says:

        Take your time coming back up; wouldn’t want you to get the bends.

      2. JL says:

        URLs are taking in a comment for me, so just ask the Goog about “Chloroquine Is a Zinc Ionophore” and this research paper “Zn Inhibits Coronavirus and Arterivirus RNA Polymerase Activity In Vitro and Zinc Ionophores Block the Replication of These Viruses in Cell Culture”. There’s more, but you’re a new swimmer, and I don’t have time to give advanced instruction.

      3. Dean M. says:

        Arrogant SOB…

  68. JL says:

    As if “Official Approval” is some innate property of the drug. As if with “Official Approval” it will work, and without “Official Approval”. SARS-CoV-2 is working really well without anyone’s highest honor of “Official Approval”. But it is interesting that it also took a long time for many Medical Officials to figure that out.

  69. Guest says:

    Current reporting indicates that 85% to 90% of patients in critical care who are ventilated will die within ten days. This is a terrible outcome by any measure, and certainly far worse than the results being reported in cases using HCL. There are no randomized, double-blind placebo trials to support the contention that the 10% to 15% who survive being ventilated survived *because* they were ventilated. They may well have survived anyway. In the absence of a controlled study, for all we know maybe the ventilator is what is killing these patients.

    Moreover, placing the patient on a ventilator consumes massive quantities of ICU resources which could be redirected to other cases.

    If you are going to be logically consistent, you should oppose placing patients on a ventilator until such time as a controlled study can show that the ventilator is both safe and effective for these patients. Is that your position? If not, please explain the distinction.

    1. drsnowboard says:

      ARDS is not just caused by coronavirus and mechanical ventilation is standard of care.
      If you don’t maintain oxygenation , you die, something that’s even covered in the ABC of first aid.
      The damage has been done.
      That really is a parachute vs no parachute situation…. and a strawman to boot.

    2. Dean M. says:

      PRECISELY this MD’s point!

      1. drsnowboard says:

        Oh come on, linking to a doc’s observations which are then hijacked to support a 5G radiation weapon narrative? You know this is the comments on a science blog, right? Get back to your woo

  70. Richard Fowler says:

    Yes Derek as you said you are not a “physician” and you are not a “clinician” but you like to “stick to what you are good at” You are good at what? Do you have a drug on the market? Did you left long lasting scientific achievement in the all the companies you worked for?

    may be like the rest of the world you should take confinement form your blog for couple of weeks at let people do “what they are good at”.

    1. A Nonny Mouse says:

      In your case, it is not written English in a form that we know of, so I would refrain from doing so for the duration.

    2. march21 says:

      We readers including lay people like me love Derek’s blog irrespective of his political views. He’s doing us all a service.

  71. Critical Care Doc says:

    There are many published reviews of the effects of hydroxychloroquine over the last few years which show That the drug has widespread positive effects on multiple disease states including bacterial and viral infection, including coronavirus. One example is as follows: 10.007/s12016-010-8243-x.
    The drug is used safely for porphyria cutanea tarda. It has Positive effects for diabetes, etc.
    Unfortunately, our experience with COVID19 is that nothing seems to work once profound tissue hypoxia takes place.
    Intubation is not the answer, in fact, once intubated patients don’t seem to come off.
    It seems most reasonable to try and use combination therapy including hydroxychloroquine early, coupled with high dose zinc and azithromycin.
    These therapies may have Direct and indirect effects on immunomodulation, cytokine production, antiviral effects, etc.
    There is also the notion that the virus is leading to iron dislocation from hemoglobin, and this is the real cause of its devastation.
    HCQ binds to the erythrocyte and this may be having some stabilizing effect on iron dislocation.
    In any case, novel therapies hopefully will be forthcoming such as a trial in hyperbaric oxygen.
    Many of the comments above are ill-informed and seemingly politically driven.

    1. DK says:

      Could lactoferrin (an iron binder) supplementation work similarly to hydroxychloroquine without the potential side effects?

  72. Critical Care Neuro Doc says:



    These are interesting

  73. lawrence rosen says:

    I have heard that the best combination is hydroxychlorichrone and zinc. Supposedly hydroxy opens up the virus for the zinc to enter and kill the virus. Anyone else know anything about this?

  74. Critical Care Neuro Doc says:


  75. Duane says:

    Just in case everybody didn’t already see this coming (with the exception, of course, of the Trumplican koolaid drinkers), from The Atlantic/Defense One:

    The president’s family and friends have a “financial interest” in a manufacturer of the unproven drug Hydroxychloroquine, the New York Times reported with the help of more than a dozen reporters Monday evening. Various parties within the Trump orbit that have financial stakes of Sanofi include:

    “Trump himself has a small personal financial interest in Sanofi, the French drugmaker that makes Plaquenil, the brand-name version of hydroxychloroquine.”
    “As of last year, Mr. Trump reported that his three family trusts each had investments in a Dodge & Cox mutual fund, whose largest holding was in Sanofi.”
    “Sanofi’s largest shareholders include Fisher Asset Management, the investment company run by Ken Fisher, a major donor to Republicans, including Mr. Trump.”
    “Another investor in both Sanofi and Mylan, another pharmaceutical firm, is Invesco, the fund previously run by Wilbur Ross, the commerce secretary.”
    Relatedly, “Several generic drugmakers are gearing up to produce hydroxychloroquine pills, including Amneal Pharmaceuticals, whose co-founder Chirag Patel is a member of Trump National Golf Course Bedminster in New Jersey and has golfed with Mr. Trump at least twice since he became president.”

    1. David F OBrien CRNA,APRN says:

      Please stop listening to ill informed MSNBC Morning Joe and his even more unknowing cohost!! Plus the NY times had been less then factual for years as its bias against this administration hence FAKE NEWS. The facts are is that Hydroxychloroquine and Zithromycin are generic medications plus you can buy zinc supplements over the counter. The entire 5 day course of these medication combination is under $8. Boy Trump will make a ” finanical killing” I am a healthcare professional(CRNA,APRN) and am currently on Hydroxychloroquine/zinc prophylaxis as I’m at a very high risk of exposure

    2. theg9 says:

      Copied from my response to another commenter who held a similar view to yours:

      Sanofi does not have a patent on this medication. Numerous other generic drug manufacturing companies have been making this drug for decades, and selling it for very cheap prices. There is a huge amount of disinformation being circulated right now, from all sides of the political spectrum. The narrative that Trump is somehow going to benefit significantly by pushing chloroquine is yet another example. It also indicates that people who believe this don’t know much about the workings of the pharmaceutical industry.

  76. Dirk Johnson says:


    I’d like to hear your input on this:

    While it is obviously and unfortunately politically biased, the writer seems to have some core understanding of molecular biology.

    BTW- the writer was exposed here as — Andrew Gaiziunas

    1. Derek Lowe says:

      I’m still thinking about the hemoglobin binding idea, but the author makes a number of mistakes in the rest of his argument. The coronavirus does not have DNA (RNA instead), malaria parasites are not bacteria, there are patients with unilateral opacities, etc.

      1. Dirk Johnson says:

        THANK YOU

    2. therealestg9 says:

      I have done graduate work in bioinorganic chemistry.

      Two things about this:
      1) I strongly disagree that iron is being pulled out of the porphyrin ring of the heme protein. These hemes are used as catalytically active sites in numerous enzymes in our bodies, encountering a range of chemical environments and (relatively) harsh, oxidative conditions. There is no way that a simply glycoprotein from a virus is going to be able to dislodge the iron. Heme proteins are way, way too robust for that, otherwise they wouldn’t have been found in so many of our enzymes.

      2) I believe the author is on the right track when he meningitis zinc. Do a ctrl+F search on this page for “zinc”. There have been a lot of links and information posted about zinc and its combined effects with chloroquine to provide antiviral activity.

      1. Urukai says:


        I have found some data on COVID-19 patients bloodwork and ferritin seems to be quite high in severe patients when compared to moderate patients.

        1600 ug/L when compared to the normal range of 30 to 300 ug/L.

        I know ferritin is a rather unspecific marker for inflammation but in this specific case it would be high as a response to the increased iron in circulation.


  77. Karen Kilgore says:

    I have bronchiectasis, diagnosed approximately 10 years ago. My pulmonary physician, a well-known researcher at a major university, has prescribed Azithromycin, 250 mg, three times a week, to reduce inflammation. It has helped me (anecdotal evidence) but also been tested in clinical trials. I would follow the advice of my pulmonary physician, in the event that I were diagnosed with COVID-19. He is fairly clear about the need for clinical trials and I would respect his judgement with regard to interventions. As someone, who is familiar with managing both shortness of breath and pneumonia, I would be unlikely to do anything based on hunches. I hope to avoid catching COVID-19. I hope I still have my supply of Azithromycin based on my own personal outcomes and published studies regarding bronchiectasis treatment. My decisions would be based on conversations with my trusted physician. I ca imagine refusing a ventilator. I’ve lived with chronic pulmonary distress (non-smoker) for years — not being able to breathe is terrible, but taking action based on fear and panic is worse.

  78. Sunny says:

    Hydrocychloroquine and chloroquine have severe side-effects that range from increasing the risk for QT prolongation and arrhythmias to severe depression and blindness. These are well known and described. Given that the anti-viral effects of these drugs have been studied for decades and have been found to suppress viral production to some degree (not totally!) in cell culture in vitro, but then have failed each and every time in clinical trials, it is rather irresponsible to give to patients on the mere suspicion that it might work. There is no sound clinical trial that shows that the drug or the combination of the drug with an antibiotic really helps COVID19 patients – and that if such an effect existed it outweighs the risk of the drugs. One needs to keep in mind that most patients that get severely sick do have pre-existing conditions and thus may be even more susceptible to such side-effects.

  79. Gena says:

    Guys, if something is not statistically significant it does not mean it does not work. Perhaps, just bigger studies are required and one may also look at the patients stratification to see which patients actually benefit from the treatment. One can find a lot of statistically significant correlations that are completely meaningless. The best approach is to prevent the so called “cytokine storm” by starting the treatment earlier. This way other drugs (e.g., ACE2 inhibitors or others) may be beneficial.

  80. JP Leonard says:

    As another commenter noted, since HCQ is generic, the profit is going to be modest, so the golf link could be benign. Still it’s an interesting angle. Notice that Trump hasn’t said anything about Zelenko’s HCQ + Zinc cocktail, although the news is 3 weeks old.
    Dr Cardillo is now saying HCQ doesn’t work without zinc. That means Zinc is the active ingredient, and other zinc ionophores could be substituted, stealing the show from HCQ – unless it is also has immunoregulatory functions of its own. I looked that up and found this:
    “The HCQ immunomodulatory effects are mediated by its anti-inflammatory, immunosuppressive and photoprotective properties, and interfere with lysosomal degradation.”
    The anti-inflammatory feature may be useful, but I believe the beauty of the HCQ+Zinc combination is that it activates rather than suppresses the immune response. So the two may be a balanced match. While Azithromycin has both anti-inflammatory and immunomodulatory function, it might not be needed. Cardillo claims success without it, while Zelenko prescribes all 3 drugs.
    Looks like Zinc is the golfer, HCQ is just the caddy 🙂
    I doubt if anyone is going to make a mint from zinc.

  81. John says:

    I failed to see any mention of taking 220mg of Zinc with the Hydroxychloroquine. The Zinc is the entire reason for the Hydroxychloroquine because is helps the cells absorb the mineral at a much faster rate and it prevents the virus from replicating at the rate it has been.

  82. Geoffrey Bramhall says:

    I think what this article is trying to say is not to throw over scientific principals on
    evidence that (as in the French report) show 100% recovery when on average there
    is 99% recovery with the random population. The apparent success is masked by
    the disease’s 99% regular recovery rate. A larger sample (than the French report)
    might show no net improvement or even a decline. It is so easy for the average
    citizen to be swept up in these numbers and convince themselves that there is a
    cure and why should anyone try to deny it when a life is on the line. We can hope
    and pray that it will prove to be the answer, but don’t let it get in the way of something
    that actually might be what the doctor wants.

  83. Paul Nicholas Boylan says:

    Is anyone screening for thalassemia? I am Greek and have thalassemia B. It is easily managed, but all of my doctors over the years have warned me to avoid taking malaria medicates because they are lethal to thalassemia patients. Hydroxychloroquine is a malaria treatment.

  84. orden smith says:

    no one was saying this was a cure. I want to take it because clinical evidence are mounting that it may improve my chance of getting a favorable outcome. Even with taking this I may still die, But it is appearing that this may reduce that probability. Think in the moment, not like academics who belong in a classroom with ideal situation. classroom ideals are for finding trends that mat later be applied to real world. We have people dropping daily now, so adapt what little data on different treatments for now with a risk/reward. Maybe by Winter when this come raging back the classroom academics will have time to do a better clinical trials and come back with better answer. Between now we add HCLQ+zn to the regimen of treatment based on what little evidence we have. risk vs reward here.

    1. JasonP says:

      @Orden Hey, I get the frustration that comes through and I know where you are at because I have been there too. Just like @Mustafa reports when faced with a terrible outcome one is willing to try anything. Now in a similar situation the Doctor (PCP) had no objection to using the “thing” that wasn’t approved, because as far as science was concerned it would be ineffective. But because it was “generally safe” he didn’t object. Then he said something that stuck with me like a seed a seed that didn’t grow until later: “Even the placebo effect can account for 20% of the effect.” Yeah, in the long run, it didn’t work, but it did give me some “hope” and I think that is a natural thing humans need, especially in times of crisis or uncertainty.

      So what the PCP was saying is the the mind is a powerful tool in patient outcomes and recovery, often times. So “the power of positive thinking” or thinking that one is getting “the cure” is enough to improve the outcome for some people who take a trial drug or take a sugar pill as part of a double blinded clinical trial. So with so many other factors running around in the mix, it is often hard to tease out when a drug or intervention has a positive effect. That is why we need good trials and good statistics.

      Where I agree with you is along the lines of patients should be able to accept responsibility for taking something that is “off label” or isn’t proven to a 95% confidence level to work. I think there is a difference between taking snake oil and “experimenting” with FDA approved drugs that are used off label or in a way that the FDA has not sanctioned its use.

      One of the standard arguments against this are two-fold. First it is a waste of resources. Best I can see Hydroxychloroquine (HCQ) is generic and not particularly expensive or costly to make. So where is the waste of resources? Is it an issue of racing to manufacture something that is ineffective and that violates strict codes or ethics? I dunno. Seems like if the market demands it, is willing to pay, then there is an argument against a waste of resources?

      But then there is the argument along the lines of “it isn’t effective” or hasn’t been proven to be as such. And THE HORROR! It has side effects! But wait! Every time I pick up a prescription drug, it comes with a multi-page booklet of cations and possible side effects. Plus the Pharmacist spends a few moments “counseling” me on the use and those side effects. So to toss out a drug because “it has side effects?” Meh. From this chair that is a weak argument, most all drugs have side effects.

      Along this line, HCQ is an FDA approved drug. So I would trust that anyone who took an oath to “do no harm” is not going to write the script for HCQ if the patient’s chart show they have contraindications, complications or would be a good candidate for the negative side effects. At some point, seems like we can trust the education and training of the Docs? Why not allow the Docs to “practice medicine” on an anecdotal basis especially if they are convinced it will do no harm? Seems if I remember correctly one of the levels of evidence in drug discovery is indeed anecdotal evidence – or in the literature, called a “case study.” Sure the weakest form of evidence for sure, but of some value.

      So the general thought is not wrong. Where I do object, however is some of the language and its implications. One might wish to reconsider the use of “academics” or “classroom academics!” Oh I have seen this too. On occasion, I have let myself be intimidated by smart people or those with advanced degrees. Sure there are plenty of ‘eggheads’ out there, with grandiose ideas that never make it to reality. But to put down the maven of this blog is highly unfortunate. First, this dude isn’t some academic, but a smart guy that makes his living being smart and coming up with ways to address maladies and get cures for those things that scourge humans. Apparently he is rather successful at it because 1) he’s been around for a long time (if you are a dim bulb or not particularly creative or effective, one is soon rooted out of the research environment) and 2) One of the preeminent journals in the field invited Derek to move his blog to their website and use their resources. That doesn’t happen for just any “classroom academic”. But if nothing else, the last few blog posts should be demonstrative of the abilities of the writer: complex topics have been distilled down to a level that most can appreciate.

      So as Derek points out, a scientists job is to get “just the facts Ma’am” and do it in an unbiased way. So the process looks cold, calculated and detached. In many respect it needs to be just that, to be fair and not subjective. We need to know what works and what doesn’t. So that doesn’t particularly give anyone hope or solace. Sure, humans can “see” hope in a small study or some anecdotal report of “it worked for me”. That is just being human – having hope! But hope and anecdotes don’t make for science or proof. We have to learn to accept the process and hope for a positive outcome from one of these trials.

      Alternatively we need to come up with a better or faster process or something we can do in a crisis. Maybe someday we will get there? Until then we should be grateful for those who donate their time, experience and knowledge to us to help us understand what is behind the curtain as we struggle against a foe we can’t see.

  85. Curious says:

    The information that I have seen appears to show that hydroxyquinone alone is not adequate therapy, but that using zinc and an antibiotic in addition EARLY makes a difference. Understanding why the drug works for malaria patients, the addition of zinc which has been shown to have an antiviral effect and an antibiotic to handle opportunistic organisms would seem to explain this. Why are doctors reporting both lungs involved to the same extent? The rapid decline of lung function paired with hypoxia suggests that the virus is acting on blood cells and not the lungs.

  86. BobE says:

    There are two separate questions here.

    First, does HCQ give any provable benefit? After months of study, we have as many questions as answers. Does it really? In which cases? In the right combination with what other drugs? At what doses? For which patients? These are all interesting questions, where even small benefits could make a difference in many lives.

    Second, is HCQ a “game changer?” In an epidemic that grows this fast, a drug that reduced mortality by 50% is not a game changer. Early virus spreads before mitigation showed doubling every three days or so. A 50% reduction is three days of distancing. It’s useful. It’s helpful. It doesn’t change the game. To change the game, HCQ would have to reduce mortality by closer to 90%. If it did that, I doubt we’d be talking about equivocal studies and ambiguous results.

    We’d all like hope. We’d all like a miracle. Hope is not a plan. Hoping for a miracle is not even the distant relative of a plan.

    1. Tom Wallace says:

      “Second, is HCQ a “game changer?” In an epidemic that grows this fast, a drug that reduced mortality by 50% is not a game changer.”

      50% isn’t the silver bullet, but a 50% reduction in severity is roughly equivalent to doubling the number of ICU beds and vents.

      The results of anecdotal support for HCQ is that the logistics issues have been solved in the US for this. Based on the anecdotal buzz, doctors had been hoarding the drug, per The NY Times. Some of the other proposed therapeutics aren’t likely to be practical to quickly dispense at scale for milder cases.

      I would like to see more evidence before the drug is dispensed to potentially millions. I think it is safe enough, but when you give it to 1,000,000 people with mild symptoms, there will be some bad outcomes, for perhaps no benefits.

      Fortunately, unlike global warming, we will have results from clinical trials soon enough.

    2. JL says:

      That’s terrible math. Sometimes people do all they can do, follow the rules precisely and even then some, and still get infected. Tell Healthcare workers that that 50% chance is meaningless.

  87. rachidi says:

    as a medical surgical practitioner having the use of several types of medical treatment and having discovered fortuitously that several drugs intended for specific pathologies would serve other diseases as it has been proven by several learned societies of this fact in front of the scale of the pamdemia would not be not wise to give a better chance to this protocol while waiting for the discovery of an adequate drug
    thank you

  88. Island Doc says:

    Belgium Task Force on Supportive Care and Antiviral/Immunologic Treatment of Hospitalized Patients With Suspected or Confirmed COVID-19 (2020)
    Would it be better if more COVID 19 reporting remove political bias, but instead focus more on what medical frontline physicians are doing to help with this crises? I would be interested in seeing more articles in this blog talking more about what doctors or scientists in different countries like China, Italy, Spain, France or New York and now Belgium (which uses Hydroxychloroquine) are doing to handle this pandemic. Thank you for keeping an open mind Derek.

  89. Geo says:

    I’m a scientist, but not a doctor, so bear with me.

    Assume that HCQ works, then the next question would be why? Why should it work at all? It is an antimalarial drug. The only way it could work would be interrupting some of the same immunological response that causes malaria to be so problematic. It is somehow strengthening, or interfering, with the same chemical pathway that Malaria uses to cause symptoms.

    Thing is, the human natural response to malaria is highly variable. Different populations have genetically produced malaria resistance, to differing degrees, using differing mechanisms, over thousands of years. Ergo, there could well be a genetic variability in the response to the HCQ, as well as a genetic variability response to COVID19. Just like malaria, some people have a natural, varying, levels of genetic immunity. It would make sense that they also have varying levels of response to the drug HCQ.

    Backing up, the implications for that are that clinical trials are going to be even MORE difficult to prove out, since your response to the virus varies along with your response to the medication. What might work swimmingly well for one group, may utterly fail for another with a slightly different genetic make up. I don’t know how you resolve this dilemma other than having massive trials with hundreds of thousands of participants in several countries. I very much doubt we’ll get that opportunity.

    1. Stephen says:

      No. HCQ disables malaria by interfering with processes in the protozoa. If HCQ disables CV, it’s a mechanism on the virus, just like ethanol. The calming of immune system is an added clinical component.

    2. therealestg9 says:

      Do a Ctrl+F on this page and look for “zinc”. There have been a lot of links and other information posted already here. One proposed explanation is that the chloroquine compound serves as a zinc ionophore and results in increased intracellular zinc concentrations. Zinc inhibits the RNA-dependent RNA polymerase which slows down viral replication considerably. If this is true, then just testing chloroquine is not useful because not everyone will have adequate zinc levels in their bodies. People with conditions like hypertension and diabetes also have lower zinc levels (see the links I mentioned).

      1. LEEPERMAX says:

        Exactly . . . Ain’t gonna work without ZINC SULPHATE

  90. Question: Does anybody on this list treat AIDS patients?

  91. Mike Bentley says:

    I was corrected elsewhere, and notice that Derek said the Swedish hospitals have stopped using HCQ. The English translation of the article at says they stopped using chloroquine, not hydroxychloroquine.

  92. LEEPERMAX says:

    Hydroxychloroquine MUST include ZINC SULPHATE

  93. Aaron Fraser says:

    The best way to put this is to quote/paraphrase Zelenko, “scientists are treating this as a peacetime problem”. If you are doctor and you are waiting for “proven” treatments, you are harming your patients. Clearly there needs to be a risk/benefit assessment, but in the current situation, a drug like Hydroxychloroquine along with zinc should not be shelved waiting for the “perfect” clinical trial to finish. Chloroquine has been used in one form another since 1600s! At this point saying hydroxychloroquine and zinc are unproven is similar to saying ibuprofen is unproven for headaches while in airplanes.

  94. Agil says:

    Others are using doxycycline. There is a physician using it in a nursing home at Long Island, and will also be used in the clinical trial for preventive use at Detroit in WHIP COVID-19 Study, a 3,000+ subject look at whether the drug prevents front-line workers from contracting the virus.

    “Since we’re talking about the elderly being the most vulnerable, or people with underlying conditions, there is a theoretical benefit of doxycycline over azithromycin because doxycycline is not associated with cardiovascular disease,” said Dr. Sten H. Vermund, the dean of the Yale School of Public Health.

  95. Nocent says:

    Mr. Lowe, thank you for a well written and reasoned article. Might I make a bold statement: death is resistant to the placebo effect. With that said I make a suggestion for a study without placebo. Three groups, hydroxychloroquine, azithromycin, and combination of the two. Selection of the groups based on QTc day 0 and day 2 > 500 ms excluded or treated with magnesium with repeat EKG. Entry into groups is placement on ventilator or entry into hospital .All groups receive treatment, selection bias against cardiovascular disease balanced by improved safety profile. Then measure death outcome at 1, 3 and 6 weeks. Control group would either be historic outcomes from last month or similar socioeconomc group from neighboring hospital(s) and preferably both. This brings hope of being on a treatment with real world practice.

  96. Truth9834 says:

    A new interview with Doctor Zelenko.

  97. Truth9834 says:

    Long Island doctor tries new twist on hydroxychloroquine for elderly COVID-19 patients.

    Instead of using azithromycin he uses Doxycycline (which is an anti-inflammatory with properties similar to azithromycin but without the safety concerns and without cardiac toxicity).

    1. brian says:

      Doxycycline. Makes sense. Correct me if I’m wrong, but doesn’t an infected patient’s own immune response cause many of the symptoms and contribute to mortality? One’s respiratory system is not an ideal place for excessive inflammation.

      For patients without heart conditions, why not give all three?

  98. psoun says:

    Interesting discussion. Going to throw out an idea – I am not a lab scientist, so if this is way off course, I’m happy to be wrong.

    This preliminary research on IL-6 levels is interesting:

    Assuming future research validates this through larger trials, as HCQ has suppressive effects on IL-6, is this the primary mechanism by which it affects patients with Covid? If so, then perhaps the reported metrics associated with viral load and clearance time will necessarily be noisy because the effect of HCQ will be indirect through IL-6 levels and not by reducing virus on its own given heterogeneity in people’s immune systems. Perhaps metrics on IL-6 levels, admissions to ICU/need for ventilation, survival rates, etc. are more relevant to judge if HCQ works?

  99. Urukai says:

    Hi Derek,

    how is it possible that FDA is approving the following trial?

    The treatment is a combination of:

    Vitamin D
    Vitamin C

    for a maximum of 24 weeks and the main inclusion criteria being:

    – Healthy
    – RT-PCR positive for COVID-19

    Then the main endpoint is lack of symptons and testing negative.

    Assuming that 80% of infected have mild symptoms and resolve naturally with paracetamol only, this study without control group and in 60 subjects is basically a license for snake oil since around 80% of the subjects will be cured by the end.

    This is more of a safety trial to check the potential for interactions between the different drugs than to test any efficacy.

    Either I am missing something or I find it surreal that FDA approved this protocol.

  100. Mustafa says:

    My husband and I were both tested positive for SARS-CoV-2 (COVID-19) on Mar 22 in NYC. I’m extremely rational person a data driven and I don’t believe in opinions, I believe in hard facts and numbers (typical banking professional). Mummy husband was hit hard and albeit his vitals didn’t breach the critical thresholds his symptoms were very severe with extreme shortness of breath (he also has asthma and high tendency for pneumonia and bronchitis) and severe cough. He was gasping for air and ERs all over the city just dismissed him. I know it’s difficult to relate when you are not the one panicking for not being able to breath and I know you spent your life doing drug discovery without patient interaction, but if you had to go through this with ZERO help from failed states all over the world resulting in collapse of healthcare system you would not only take HCQ/AZ cocktail, you’d probably take Botulinum toxin/Dimethyl Cadmium cocktail if you were told it could help you breath and stop that feeling of drowning inside out. The scientific society is extremely slow compared to the speed at which people are contracting and dying from the novel coronavirus. The 1%, 10%, 0.01%! Who cares? The fact that matters is that EVERY PERSON DYING FROM THIS WHILE STATES AND GOVERNMENTS AND SCIENTISTS ARE TAKING THEIR TIME is someone important to someone else.

    HCQ/AZ helped my husband to be able to breath again and even though he’s still not very well he’s 10 times better than when we were dismissed from the ER. What’s gonna happen after the meds are over? I don’t know! But with lack of alternative we had to choose something and we chose to experiment over suffering and death.

    1. JP Leonard says:

      Dear Mustafa,
      Glad your husband is doing better with HCQ/AZ! Are you able to add zinc? Dr Zelenko in NY claims 100% cure with HCQ/AZ/ZN.
      “Zelenko has been prescribing a treatment plan of 200mg of hydroxychloroquine twice a day for 5 days, Azithromycin 500mg antibiotics once a day for 5 days, and 220mg of Zinc sulfate once a day for 5 days…. Fox News’s Sean Hannity read from the doctor’s regimen during an interview with Vice President Mike Pence, who is leading the White House Coronavirus Task Force.”
      Wow, So it’s been on Fox and ABC News (they also had Dr. Cardillo on) and it’s even been delivered direct to the White House.
      Stay wel, JP

  101. Sulphonamide says:

    “So as for my contribution to fighting the coronavirus, well, you’re looking a significant part of it right now. I can curate and annotate the news, add my own opinions after thirty years of drug discovery work and (I hope) make people smarter about what’s going on.”

    And quite possibly do that as well as anyone in the world could. The debt of gratitude many of us owe to Derek, built up over many years, continues to grow. When Nature Briefing links to your blog, to tell it how it (reasonably) “is” on a topic, it gets rather hard for anyone to deny the influence of – and lack of unreasonable bias in – your opinions.

  102. Otto Mann says:

    Thanks for pure, clear sanity.

    And where did all this trolling come from? Thank Defective Donnie for that. With the help of geniuses like Dr. Oz, Laura Ingram and Jared Kushner, DT spun a fantasy for fools to grasp at. Some call that “giving hope to people.” I call it fraudulent manipulation.

    The saddest thing is that the global response to COVID is unprecedented, and thousands of scientists are working around the clock on any number of potentially viable treatments and vaccines. These will roll out more rapidly than at any time in history. Expect a death-reducing, ICU-avoiding, legit treatment to be in use within 3 months — hopefully one with not too many hurdles to scaling distribution. I would not even be surprised by a vaccine coming out this year.

    1. chemist says:

      You’re a weak-minded and sad individual for placing politics above solving a humanitarian problem.

  103. Mike Moorman says:

    Very interesting and worthwhile article. Your parachute analogy caught my attention. While we know that the use of a parachute is much more efficacious than no parachute (placebo), so it would be unethical to do a placebo controlled study. To continue the analogy, you would need to do a large open label or real world study to fully understand the safety profile. Mortality is approximately 1 out of 100,000 jumps. I suspect broken bones, etc are much higher.

  104. Raphael Stricker says:

    OK, let me rephrase the question: Does anybody on this list treat AIDS patients or know anything about AIDS treatment? I think that I heard this discussion in 1987.

  105. Michael Ameres says:

    Are trials of early disease including Zinc? That is one of the proposed mechanisms of action of Hydroxychloroquine, facilitating zinc entry into cells.

    1. Rodney says:

      Exactly, the doctor has to give you Zinc. How do these other professionals not know this?

      Dr. Anthony Cardillo said he has seen very promising results when prescribing hydroxychloroquine in combination with zinc for the most severely-ill COVID-19 patients.

      “Every patient I’ve prescribed it to has been very, very ill and within 8 to 12 hours, they were basically symptom-free,” Cardillo told Eyewitness News. “So clinically I am seeing a resolution.”

      Cardillo is the CEO of Mend Urgent Care, which has locations in Sherman Oaks, Van Nuys and Burbank.

      He said he has found it only works if combined with zinc. The drug, he said, opens a channel for the zinc to enter the cell and block virus replication.

      He added that the drug should not be prescribed for those who are presenting only mild symptoms, as there are concerns about shortages for patients with other conditions who need to take the drug on a regular basis.

      Plus Dr. Zalenko:

  106. Richard Long says:

    “Update 2: some Swedish hospitals are reporting that they have stopped administering hydroxychloroquine and the HCQ/AZ combination due to lack of evidence and worries about adverse reactions.” If you read the actual article, they discontinued use of the older Chloroquine not the far safer and more effective Hydroxychloroquine. Would you issue an update 3 to correct this error?

  107. JP Leonard says:
    Here’s that 9 minute video demonstrating RNA transcription, how the virus replicates inside the cell, and showing how Zinc blocks viral replication in the cell as per the title of the study,* “Zn(2+) inhibits coronavirus and arterivirus RNA polymerase activity in vitro and zinc ionophores block the replication of these viruses in cell culture,” shows how an ionophore pulls the Zn across the cell membrane into the cytoplasm. Explains experiment showing how increasing the amount of Zinc or ionophore increases the virus blocking effect. “And here’s what they found in their experiments. They use SARS-CoV, the pathogen causing SARS. And they found if they added more zinc to their experiments, less viral RNA. So zinc could actually block viral reproduction… Now, here’s the explanation why chloroquine might be effective in the treatment of COVID-19, because it is a zinc ionophore in and of itself. In this paper, they used ovarian cancer cells to prove that chloroquine enhanced zinc uptake by these cells. (Explain tables of results) You can see that increasing doses of chloroquine cause increasing concentrations of zinc inside the cell. Similary, more zinc was found inside the cell with increasing zinc concentrations outside the cell and at each concentration of zinc, this effect was augmented by adding chloroquine to the experiment…. So obviously the addition of chloroquine had a really, really big effect on intracellular zinc, much more so than just adding zinc alone. If you want to improve your understanding of epidemiology, make sure to register for a free Medmaster trial account and attend our Epidemiology Essentials Course. We’ve just opened it up to trial users due to the huge demand.”
    674,000 views since Mar.17, 57.3 K subscribers.
    The ionophore in the video is pyrithione rather than hydroxychloroquine. Since so many people seem to object to HCQ, I have looked around to see if there are other zinc ionophores, but there doesn’t seem to be a whole lot choose from. (Pyrithione is a natural substance C5H5NOS and should not be confused with zinc pyrithione C10H8N2O2S2Zn which is an ingredient in dandruff shampoos and is very toxic.)
    Looking up pyrithione as ionophore led me to an interesting paper on the Wiley Online Library. from February. Two Chinese doctors offer a pharmacopoeia of China’s experience with the virus, including a whole array of nutritional interventions (vitamins, minerals, interferons etc.) Then they say,
    “Zinc deficiency results in dysfunction of both humoral and cell‐mediated immunity and increases susceptibility to infectious diseases.42 Zinc supplement given to zinc‐deficient children could reduce measles‐related morbidity and mortality caused by lower respiratory tract infections.43 Increasing the concentration of intracellular zinc with zinc‐ionophores like pyrithione can efficiently impair the replication of a variety of RNA viruses.44 In addition, the combination of zinc and pyrithione at low concentrations inhibits the replication of SARS coronavirus (SARS‐CoV).44 Therefore, zinc supplement may have effect not only on COVID‐19‐related symptom like diarrhea and lower respiratory tract infection, but also on COVID‐19 itself.”
    Oddly enough, altho the Chinese looked at Chloroquine, they didn’t mention its zinc ionosphore feature. I don’t believe Raoult did either. It seems we have an amazing ability to ignore zinc when it’s foundational to the immune system, but then, there is always more than one thing going on – like the old French RR XING warning, “One train can hide another.” CQ and HCQ aren’t ONLY ionosphores.
    From the Chinese entry on CQ: “chloroquine was also found to be a potent inhibitor of SARS coronavirus infection through interfering with ACE2, one of cell surface binding sites for S protein of SARS‐CoV.”

  108. Truth9834 says:

    S. Korea reports first successful case of convalescent plasma therapy for COVID-19 patients

  109. Brian says:

    The good news is that eventually we’ll have the data from several high quality clinical trials and all this speculating, guessing, and hoping can end. Which, of course, is kinda why things are done that way.

    If doctors want to prescribe it, or patients want to take it, then I think they should be able to, which seems like is the case in a lot of places. But scientists and doctors also have the responsibility to accurately interpret the current data. The current data is weak. In the future that may change, but right now, that’s where we’re at.

  110. Alan Troy, MD says:

    It is hard not to be skeptical, since successful antiviral therapies have taken decades to develop, e.g. Hep C, HIV, etc, not to mention the multitude for which no antiviral has been successful. The hazards of untested therapies have all too often proven greater than initially appreciated, e.g. antiarrhythmics for ventricular arrhythmia, NOACs for mechanical heart valves, cisapride for GERD, Vioxx for DJD, etc. Primum non nocere.

  111. JP Leonard says:

    Here is the video of the Hannity-Pence phone call where Hannity reads out Zelenko’s dosages for HCQ, AZ and ZN.
    Pence responds that “what we see in those anecdotal studies we’re going to put to the test.”
    OK, well Zelenko has been making these claims for almost a month. Where is the test? If he is not making this up about a100% cure rate, we could have saved 1000’s of lives and trillions in losses, if they had put it to the test right away.
    I still can’t believe when a godsend like this is reported by a licensed MD – two of them now with Dr. Cardillo in LA – that the city, county, state or federal health department can’t send someone to check it out. Look at his charts, talk to a random sample of patients. UCLA could send an intern for goodness sakes. No but that isn’t anybody’s job. This is anarchy. This is incompetence, dysfunctional, botched beyond belief. People are dying while Nero fiddles.
    I’ve had to design my own online crash course on zinc vs. viruses to try and indirectly confirm that this therapy is at least plausible. Spent a lot of time on it the last few weeks. I am trying to share it so people will at least consider that the 2 doctors could be on to something.
    Of course Pence doesn’t even mention zinc in his reply, nor does the text accompanying the video.
    There is an order of magnitude more press about allegations Zelenko exaggerated the number of sick patients in his village or his practice, than there is about his treatment.
    Why do people get distracted by red herrings and politics instead of focusing on important opportunities?
    We have peer reviewed studies reporting that zinc is effective against viruses, yet 99% of pundits and medical professionals turn up their nose at it, why, because it’s just a plain common mineral, nothing fancy? Sort of like Cinderella, fated to be ignored.

    1. theg9 says:

      That article you posted is simply ludicrous with its bias and slanted journalism. They make no effort to investigate if in fact, the doctor got a 100% success rate with zinc and hydroxychloroquine. Rather, they point to a failed prediction of his, in which he wrongly predicted that the infection rate of a particular town would be high, but in reality it turned out to be low. And they’re using this one failed prediction about an infection rate to paint his entire hypothesis as invalid?

      Here’s why I think this has been flying under the radar so much:

      Worst care scenario: The pharmaceutical companies can’t make any profits off a generic drug (hydroxychloroquine) and a mineral (zinc) so they’re going to try to find another route for achieving the same end goal.

      Best case scenario: Arrogance. “Oh, it’s just a simple mineral, there must be some reason why other people aren’t trying this, so we’re not going to bother trying it.”

      The truth might lie somewhere between these two extremes. If it’s leaning more towards the best case scenario, then at least people can raise awareness about this proposed mechanism of action of HCQ/zinc and persuade actual doctors (who are already treating patients using only HCQ) to try it out.

      1. Donna says:

        I’m a lay person reading. I’ve enjoy reading and not commenting, because I’m here to learn. However, I think this might answer your question about Zelenko.

  112. JP Leonard says:
    My earlier post was so long that people might overlook the part where Chinese researchers recommended to *Combine Zinc with a Zinc Ionophore* back on February 13.
    “Increasing the concentration of intracellular zinc with zinc‐ionophores like pyrithione can efficiently impair the replication of a variety of RNA viruses.44 In addition, the combination of zinc and pyrithione at low concentrations inhibits the replication of SARS coronavirus (SARS‐CoV).44 Therefore, zinc supplement may have effect not only on COVID‐19‐related symptom like diarrhea and lower respiratory tract infection, but also on COVID‐19 itself.”
    Of course the zinc concentration will still work if you use Hydroxychloroquine for a zinc ionophore instead.
    By the way, China had no new deaths yesterday. USA had almost 2000.
    While we waste our time arguing about whether to call it the Chinese virus. Listen up to the Chinese advice instead, people!

    1. Zeke says:

      Reduction of excessive cytokine production may also reduce cardiopulmonary damage which is why if you are going to use it you should use it early in high risk patients.

  113. Thomas says:

    Derek, I was drowning in day 6 and took the malaria dose of Quinine. I felt relief in a few hours. It wasn’t a cure but it got me through the drowning episodes.

    Every time my quinine got low I could feel the virus coming back. Quinines half life is only 8-12 hours whereas HCQ is 42 days so I could really feel the difference in the virus getting stronger after the quinine got low.

    Does this correlation in me in itself intrigue you as being actual evidence?
    now after 23 days of shortness of breath I can breath again

    Of course Quinine is nasty compared to HCQ but I wasn’t able to get HCQ

    1. tristan says:

      Hydroxychloroquine half-life is 22 days, not 42 days.

  114. JP Leonard says:

    Extraordinary claims require extraordinary evidence? But the claim is not all that extraordinary. People recover from respiratory viruses all the time, thanks to their immune system. What HCQ+Zn does is help your immune system do its job. What would be extraordinary is if any of this synthetic weirdness they love to work on did anything against a virus.

    Why such resistance? Inertia, groupthink, the usual resistance to new ideas? It’s easier to argue about details than taking action? No money to be made in zinc, except in buying up assets cheap now before we revive the economy? No money to be made from a working immune system, or from healthy nutrition. Could be all of those things.

    Innovation is wunnerful. Our immune system has been innovating for a billion years to get us here. Can we please let it have the minerals it needs?

  115. Truth9834 says:

    Take a look at this non-peer reviewed study

    Maybe the way to go is Hydroxychloroquine with zinc supplements? This is the approach used by the LA doctor – – thoughts?

  116. Truth9834 says:

    Zinc for the common cold—not if, but when

    1. JP Leonard says:

      Hi Truth9834, the abstract says,
      “A new meta-analysis shows that zinc supplementation can reduce the duration and severity of a cold, if it’s started early on.”
      Could the reason be that later on there is too much virus ?
      What if you could take a zinc ionophore along with the zinc, that would multiply the effect so it might work also in a later phase?
      “zinc lozenges reduce the duration of cold symptoms by 12% to 48%, but only at daily doses >75 mg”
      The HCQ-Zinc cocktail is 200-225 mg of Zn . HCQ also works better early phase. I don’t know how late HCQ/AZ/Zn still works. I wouldn’t wait too long!

  117. Sulphonamide says:

    When zinc was first brought to my awareness (probably I was still at school, where I suffered endless colds) I tried capsules suitably loaded with it…and promptly got the worst cold of my life. When really bad debilitating flu struck my university I ate 5 oranges a day and was the only person not to get sick. Do I believe that either of these represents anything more than pure chance? Nope – though the oranges probably had some modest benefit. I had also tried garlic capsules and goodness knows whatever other products hearsay suggested would be beneficial – all to no avail. All meaningless anecdotal data. However, there are enough people like me nationwide and worldwide, desperate not to be suffering a lengthy cold 6 times a winter, that if there were anything that actually worked reliably, we would be taking it (yes, I know the joke of the 50 dollar bill that everyone walks past because obviously it must be fake or someone else would have picked it up). The evidence may eventually show that for a statistically-significant proportion of people, there will be a statistically-significant improvement in something measurable…but overall it was a clinically-meaningless waste of money. People don’t deny the benefits of zinc or any other cure because they are fools or have nefarious ulterior motives…just because it doesn’t do anything worthwhile for enough people. We would all love a cure for the common cold – in the same way as everyone reading this blog would love to see something that gives meaningful benefit for those with Covid-19 (I fear we will all have friends and family who have died from it). Likewise, we would love to eat humble pie and admit that we were wrong about zinc and HCQ….but if they are working to a really meaningful degree (a cure / reduction in recovery time etc) we would doubtless know about it already – if not, we soon will….but those who try to present these facts will still be shouted down as being complicit in some evil conspiracy. We all want cures for everything – especially Covid-19 – we don’t deny anything that is of genuine benefit (and yes, were it me seriously ill, I would probably be taking chloroquine – but then I know I can tolerate it for extended periods, so at worst it would probably do nothing).

    And as for not acting on extraordinary claims? They do rather tend to come out on a daily basis for everything from hair loss to virility to…Covid-19. ….(genuine question – would be delighted to see some examples) have there ever been instances in which the snooty-scientist deniers have in fact been proven wrong and the snake oil was in fact a global panacea (in recent times that is – vitamin C for scurvy would be a fair response otherwise)

    1. loupgarous says:

      “And as for not acting on extraordinary claims? They do rather tend to come out on a daily basis for everything from hair loss to virility to…Covid-19. ….(genuine question – would be delighted to see some examples) have there ever been instances in which the snooty-scientist deniers have in fact been proven wrong and the snake oil was in fact a global panacea (in recent times that is – vitamin C for scurvy would be a fair response otherwise)

      Successful treatment for scurvy was not a snake oil cure. British sea captains discovered that sailors who ate fresh greens and citrus were less troubled by scurvy, and made sure their men ate plenty while at sea. The discovery of a specific preventative for scurvy involved scientists doing a lot of work to identify the thing in an anti-scorbutic diet that prevented scurvy, and “ascorbic acid” – literally “scurvy-free acid” – was discovered to be what cured a disease that killed many, and given its popular name, “vitamin C”.

    2. JP Leonard says:

      Hello, Sulphonamide,
      Thanks for sharing your sobering experience with zinc and Vitamin C.
      It nonetheless remains a fact that the elderly and people with the other co-morbidity conditions tend to suffer from zinc deficiency, as I have related earlier on this thread. Here is another source: “Zinc deficiency in elderly patients” (1993)
      “it has been estimated that people older than 65 have an intake of zinc below the 50% recommended level (2). A recent study in a group of 102 elderly European people revealed that 44% of them had Zn deficiency and 20% had high Zn deficiency (62).”
      Of course, you wouldn’t try to cure Covid-19 with zinc supplementation alone. An ionophore (like HCQ) is needed to get an extra high level of zinc into the cells, to meet the viral load challenge of Covid-19.
      With dietary intake there is always the problem of bio-availability. I couldn’t find any good explanation why elderly people and those with co-morbidity conditions are not able to absorb enough zinc from their diet.

  118. loupgarous says:

    For those of us repeating the New York Times story that Trump has YUGE investment in Sanofi, a manufacturer of hydroxychloroquine, that story has been debunked as “mostly false” by I don’t like anyone, including Trump, creating hoopla from a dark, smelly place. Nor do I like the New York Times running defamatory stories their business model depends on going viral from the same dark, smelly place.

    The fact is (from that as most billionaires do, Trump had the J.P. Morgan bank administer a family trust, which invested in several mutual funds, one of which put some of Trump’s money in Sanofi. Which is a good investment for several reasons, as many long-time commenters here can attest.

  119. Demetrio Freitas says:

    Everyone have been follow the recent controversy regarding the use of hydroxychloroquine in the treatment / prophylaxis of COVID-19.

    Unfortunately, it is safe to say that a definitive answer about the possible benefit of this medication should take a few months, which is the time necessary to obtain the first results of clinical trials with more careful methodology that are in progress.

    However, there may be some prior information obtained from monitoring patients who are already using this medication continuously since before the pandemic, such as, for example, patients diagnosed with lupus erythematosus. Using very primary reasoning, if hydroxychloroquine brings any benefit in the prophylaxis or treatment of COVID-19, it is very reasonable to expect that this particular population has a different epidemiology, due to some hypothetical protective effect of the medication.

    Thus, I ask whether there is any study worldwide on the incidence of COVID-19 in individuals who had previously used chloroquine / hydroxychloroquine regularly, such as rheumatological patients.

    In places like Italy / Spain / China / USA, it is possible that there are a sufficient number of COVID-19 positives to allow a comparison of prevalence. That is, a comparison of the incidence of COVID-19 cases in the general population versus continuous users of hydroxychloroquine.

    Kind regards,

    1. JP Leonard says:

      Dear Demetrio,
      You commented that “it is safe to say that a definitive answer about the possible benefit of this medication should take a few months.”
      Conversely I would say it is very dangerous to our health to wait months, when the worldwide death toll is supposed to be around 6000 daily.
      We already have 2 MD’s who have tried it and announced they are getting 100% cure rate.
      Another MD has written an explanation in lay terms why it works.
      Chinese researchers have also said this will work.

      1. Treatment with HCQ and zinc only – Dr. Cardillo
      LA doctor seeing success with hydroxychloroquine to treat COVID-19

      2. With HCQ+AZ+Zn
      NY Dr. Vladimir Zelenko: Cocktail of HCQ, Zinc Sulfate and Azithromycin showing phenomenal results with 900 coronavirus patients treated –

      3. Nevada MD explains why zinc ionophore therapy works

      4 Re Chinese research, I have posted many references to the literature supporting the zinc ionophore therapy on this thread e.g. where the Chinese found that zinc with an ionophore “inhibits the replication of SARS coronavirus.”

      What we need now is for more doctors to try this therapy and publicly corroborate the results of Drs. Zelenko and Cardillo. I’m going to ask my doctor if he can do this, but I’m not too optimistic because he works for a large clinic. The 3 doctors above have their own independent practices. I’d be very surprised if corrupt agencies like the WHO or CDC would run a trial of HCQ+Zn, when these medications cost less than $10 per treatment.

  120. harry says:

    Rather than guessing which medications might work as effective treatments of Covid-19, has anyone done a statistical analysis of comorbidities of people who have had serious respiratory symptoms. Since over 88,000 have died, one would expect that we would have reasonable comorbidity data on around 200,000 cases.

    If there are significant differences in the statistical occurrence of particular comorbidities amongst this sample, it would indicate that the drugs that are commonly used for those diseases have an effect on the severity of covid-19 infection.

    For example, in the US with over 16,000 deaths particularly amongst the aged, if there were statistically fewer lupus sufferers amongst the dead and serious cases, one could some positive effect of hydroxychloroquine without having to wait for clinical trial data.
    With say 100,000 serious cases, we should be seeing ~200 people with lupus. Do we?
    The same analysis can be conducted on other chronic diseases to narrow down the likely medications that have some positive effect.

    1. Robert Clark says:

      Yes. Lots of people are asking this same question and it is mystifying why nobody in any country seems to doing those statistical studies. Rather than taking months as with a drug trial, this could be done in days since you’re just collating data already collected, health histories, and the like.

      Robert Clark

  121. JP Leonard says:

    (2020). Does Zinc Supplementation Enhance the Clinical Efficacy of Chloroquine/Hydroxychloroquine to Win Todays Battle Against COVID-19?. 10.20944/preprints202004.0124.v1.
    Currently, drug repurposing is an alternative to novel drug development for the treatment of COVID-19 patients. The antimalarial drug chloroquine (CQ) and its metabolite hydroxychloroquine (HCQ) are currently being tested in several clinical studies as potential candidates to limit SARS-CoV-2-mediated morbidity and mortality. CQ and HCQ (CQ/HCQ) inhibit pH-dependent steps of SARS-CoV-2 replication by increasing pH in intracellular vesicles and interfere with virus particle delivery into host cells. Besides direct antiviral effects, CQ/HCQ specifically target extracellular zinc to intracellular lysosomes where it interferes with RNA-dependent RNA polymerase activity and coronavirus replication. As zinc deficiency frequently occurs in elderly patients and in those with cardiovascular disease, chronic pulmonary disease, or diabetes, we hypothesize that CQ/HCQ plus zinc supplementation may be more effective in reducing COVID-19 morbidity and mortality than CQ or HCQ in monotherapy. Therefore, CQ/HCQ in combination with zinc should be considered as additional study arm for COVID-19 clinical trials.

  122. Cyth says:

    We don’t know who will recover and who will not recover without any treatment other than what’s called “palliative”. I currently seems as though around 95% to 99% of people will recover “on their own” with good nursing care without drugs. So how can we know, without controlled trials, what difference a particular drug or combination of drugs makes?

  123. Frank d says:

    *(printed on the front of every bottle produced by big Pharma and the pseudo-intellectual‘s running the FDA.)

  124. Vaclav Subrt says:

    Well, we need more data from large-scale use of hydroxychloroquin but we’re not gonna get them until physicians remain reluctant to prescribe it due to its alleged adverse effects. As what I’ve heard on the topic, only chloroquin is associated with severe adverse effects, while hydroxychloroquin not (just usual contraindications). I am aware though that not every patient is the same and can be safely treated the same way.
    There is growing consensus among medical care professionals that hydroxychloroquin treatment is promissing, it is not unknown drug, it’s approved (though for other illness’ treatment), not a “killer medicament” with severe adverse effects. On the top of that all: it is available and relatively cheap. So, I think, it is a clearcut case: we should use it in the treatment of covid-19 as much as possible. But this seems not to be taking place so far.
    It is easy to mock politicians like Trump or Macron for pushing this without having a strong evidence that it works. But they’re absolutely right in some sense. In unprecedented situation like this there is no time to process trials, make peered studies and meet all standards as usual. It is necessary to make decisions based on unsufficient evidence, even medical ones, although I can understand why proffesionals are not comfort with that.

    1. ToXDoX says:

      There’s literally a randomized control trial coming out from UMN within a couple of weeks that has a n = 8000 or so. The growing consensus that it doesn’t work because…maybe…it doesn’t work.

      Grab your 5G tinfoil hats before then and buy up those chloroquine tablets before the prices goes high! High! High!

      1. theasdgamer says:

        Maybe patients take zinc supplements without their doctors’ knowledge and maybe the doc doesn’t ask them during history so maybe the HCQ/zpak cocktail or HCQ mono only APPEAR effective and it’s the HCQ/zinc that is REALLY effective?

      2. theasdgamer says:

        And isn’t it interesting that it’s the red states that are doing the best while the blue states have the highest mortality from covid. And it’s being reported that only 18% of democrats say that they would take HCQ while 53% of republicans say that they would take it.

  125. Bernard says:

    The published update of the Raoult’s treatment HCQ-AZ are there:
    Tests on 1061 patients positive to COVOD-19 .
    Until now
    Positives treated at the IHU Marseille 2397 -> 10 deaths
    AT Marseille Hospitals system including IHU acting with the same protocol
    Treated: 3998 Deaths: 39

  126. Sarah says:

    I have had scleroderma, Sjogrens, Raynauds, Barrett’s Esophagus for 12 years (dx date). Last month’s labs show I had hyperuricemia along with a CRP of 15.4 (inflammation marker) and an echocardiogram I had developed left ventricle hypertrophy (not present in 2017). I have taken 400mg of hydroxychloroquine every day since August 2008 with no negative side effects or retinal toxicity. I also give myself weekly injections of methotrexate since 2013 along with a plethora of other drugs.

    My husband and 13 yr-old son got COVID, both are very healthy normally, and got moderately ill with fever, cough, and shortness of breath. Despite not isolating, I only got some abnormal joint pain, stomach upset, and a slight fever (<100). I never developed lung involved symptoms and didn’t experience any increased shortness of breath beyond my normal. My PCP for 20+ years prescribed a Z-pac with supplemental zinc and vitamin C for me when the boys got sick.

    Anecdotal, yes. But I’m high risk and catch these bugs very easily, including influenza despite vaccines. Somehow I came through unscathed. Maybe it was the Plaquenil combination, dumb luck, or just the Grace of God. Maybe a study should analyze rheumatology patients like me with a history of long-term Plaquenil use and our susceptibility to COVID-19.

  127. Gogs says:

    Hi can you write something about the ivermectin medicine. Its been found to stop virus growth in lab trials….

    1. Len says:

      Gogs, this report by LeonCaly, et al. may interest you.
      The FDA-approved Drug Ivermectin inhibits the replication of SARS-CoV-2 in vitro

      They stated “This Brief Report raises the possibility that ivermectin could be a useful antiviral to limit SARS-CoV-2, in similar fashion to those already reported [5 refs]; until one of these is proven to be beneficial in a clinical setting, all should be pursued as rapidly as possible.”

  128. Len says:

    Re: Supplemental zinc enhancing the clinical efficacy of Chloroquine/Hydroxychloroquine (M Scholz & R Derwand, DOI: 10.20944/preprints202004.0124.v1).

    Perhaps zinc supplementation by itself would be a good course of therapy. It is well known that zinc at normal levels in blood optimizes the immune response and it is increasingly being shown to regulate the anti-inflammatory response whereby cytokine cascade is mitigated.(1) Meenakshi Kar, et al.(2) reported that modulation of zinc homeostasis during virus infection in vitro could be a component of host antiviral response and altering zinc homeostasis may act as a potent antiviral strategy against flaviviruses (dengue virus and Japanese encephalitis virus were studied) by activating NF-kappaB leading to induction of interferon signaling.

    In a review by Scott Read, et al. The Role of Zinc in Antiviral Immunity,(3) concludes that “… zinc treatment applied at a therapeutic dose and in the right form has the potential to drastically improve the clearance of both chronic and acute viral infections, as well as their accompanying pathologies and symptoms. Consequently, the role of zinc as an antiviral can be separated into 2 categories: 1) zinc supplementation implemented to improve the antiviral response and systemic immunity in patients with zinc deficiency, and 2) zinc treatment performed to specifically inhibit viral replication or infection-related symptoms.”

    Zinc supplementation when given to Thai children (2 to 60 months old) for just 2 to 6 days was found to reduce the number of days they were afflicted with Acute Lower Respiratory Tract Infections, as well as their stay in hospital.(4) In addition to the primary result, the study also suggests supplemented zinc may be able to begin providing benefit early during infection. However, the elderly may take longer because of their “associated malabsorption” that my wife cautions me may actually (and/or) be a result of poor eating habits including when they may not be hungry for whatever reason some days.

    I am unaware if zinc supplementation has been tried or if serum zinc levels of Covid-19 patients are or have been determined upon hospitalization. Since hypozincemia is strongly associated with poor outcomes in infectious diseases, knowing a patient’s zinc status should be useful to guide therapy for any infectious disease patient.

    This view begs the question, does a Covid-19 patient’s zinc blood level predict the severity of desease & outcome? If it does, supplemental zinc provided to those who are hypozincemic may achieve better outcomes and less mortality. Since every patient’s zinc status can be determined, would not knowing it be the medically smart thing to do?

    1. Magdalena Jarosz, et al. Antioxidant and anti-inflammatory effects of zinc. Zinc-dependent NF-κB signaling.

  129. Anthony S.Pervan says:

    Administration of Hydroxychloroquine + Azithromycin does NOT stop the increase in viral load.

    ZINC SULFATE is the chemical compound that stops the viral load increase.

    SO, the “drug cocktail” to treat COVID-19 patients is : hydroxychloroquine+azithromycin+ZINC SULFATE.

    ZINC SULFATE is the “key” and why it is capitalized.

    COVID-19 patients are being SAVED in NY, FL, MI, and CA. I “know for a fact” that ZINC SULFATE was included in the New York and California “drug cocktails.” Given the extremely fast improvement in breathing in the Florida and Michigan patients, I assume ZINC SULFATE was included.

    I do not think Dr. OZ is pedaling “CRAP.” I believe any treatment that involves hydroxychloroquine is resisted BECAUSE “Doctor” TRUMP uttered the word “hydroxychloroquine.”

    I conclude that Liberals would rather diminish Trump than save lives.

    1. JermRem says:

      Anthony is absolutely 100% correct. Hydroxychloriquine opens the doors (if you will) on the cell membrane, which allows ZINC Sulfate to enter the cell and interrupt the mitochondria. This stops cell replication. Honestly, the whole article appears to be mostly slanted against hydroxychloriquine. Maybe if the author were to look a little further into which meds in combination were 100% effective instead of just one insignificant example with only 2 of the 3 drugs (missing the most important-ZINC), more people would get the truth in order to “do no harm” by having people scared of a drug that’s been around for 60+ years and is very tolerable even for 2 yr old children as prophylaxis for malaria.

      1. theasdgamer says:

        Zinc gluconate is preferable to zinc sulfate since there is less of the toxic cadmium salt in the supplement. I would like to see HCQ/zinc as one of the study arms tried somewhere.

        Zinc is essential, but a zinc ionophore is also essential.

        As of now, the best evidence is anecdotal for HCQ /inc, but it is quite strong. I’d like to see clinical trials so that we get better evidence.

    2. theasdgamer says:

      Zinc gluconate is preferable to zinc sulfate since there is less of the toxic cadmium salt in the supplement. I would like to see HCQ/zinc as one of the study arms tried somewhere.

      As of now, the best evidence is anecdotal, but it is quite strong. I’d like to see clinical trials so that we get better evidence.

  130. Elizabeth says:

    For people who’ve safely taken a Z-Pak (several times) before, like myself, and who have been prescribed Plaquenil for Sjogren’s Syndrome (but who opted not to take it because of long-term potential adverse vision impact – I have a 3-month supply lying around somewhere), I’d be more than happy to try this “cocktail” if I come down with COVID-19. These two drugs do not sound that dangerous. A bit wary about the potential cardiac side effects, but if I’m monitored for that, I’d have no problem trying this as an experimental treatment for COVID.

  131. Felipe Tiosse says:

    I agree that we cannot create hope like miracles when we talk about medications, but when you said that we cannot believe in articles without representative data you shoot down in your foot.

    Your article have a population with 11 people with several deseases and probably with this new virus they haven’t big recovery chances with any other treatment.

    Just my opinion!!

  132. Ed O’Connor says:

    I understand that lead, arsenic and cyanide completely disable the virus and prevent infection. There is even a possibility of surviving the “cure”. Copper bracelets, socks and girdles seem to be preventative. For a nominal fee a wicka will bestow a protective spell. For a few dollars more you can smear lambs blood on your door, non Jews and non moslems can use beef chicken or pork.

  133. Larry says:

    I find these discussions fascinating. I am a physician and I have recently recertified for Advanced Cardiac Life Support. I am no cardiologist, but I do understand the QT interval. It is basically the time from depolarization of the ventricles to their repolarization. Its upper limit is 450 msec. It seems to me that an EKG should be done just before starting HCQ therapy and then after therapy has started. (The less than $100 portable unit by Kardia works great for this.) The literature shows that increasing doses of HCQ is correlated with increased QT intervals in some patients.

    It is my understanding that 200 mg twice per day of HCQ for 5 days is well tolerated by most patients. They could be followed by EKG to keep it safe.

    I think Zinc must be given. The presence or lack of Zinc in the body may be related to the plus/minus results of HCQ therapy. Giving Zn for five days makes sense to avoid Zn toxicity.

    I found the following article fascinating. It views the invasion of the cell by the virus as viewed with an electron microscope, and how Zn works to stop the replication by the virus.

    I am sure most have viewed the article. It is by Dr Zelenko.

    I would also add an antibiotic to the regimen.

    If I become Covid-19 positive, and am symptomatic, will I take the HCQ/Zn regimen?
    With EKG monitoring, absolutely.

    Remember the little Kardia unit. It will give a 6 lead EGK in one minute. Go to YouTube for the “QT interval.” You can become your own expert.

    1. Trevor Marr says:

      Hydroxychloroquine combined with Zinc was found to help, not just straight Hydroxychloroquine. I see the Left Governments saying Hydroxychloroquine is not the answer, but it appears Hydroxychloroquine combined with Zinc was found to help, not just straight Hydroxychloroquine. I question the intent of the WHO and UN and Left. There needs to be REAL discussion, not Agenda pushing from Bill Gates!

  134. JessicaJoyce says:

    many of them are infected with COVID-19 and with this low immune power . many of them leaving their life. It’s a new virus, a new disease. You are just another pretentious pseudo-intellectual.

  135. Charles McClendon says:

    Is there any scientific evidence that the lockdown has prevented the spread of Covid-19 and saved lives or is that evidence all anecdotal as well?

    1. Wendy P says:

      How scientific do you need? The math is pretty straight forward. Canada locked themselves down willingly and fast. Their infection rate per million is less than HALF of the USA who dragged their feet and spent spring break in denial. It’s one big Ven Diagram of unadulterated and unchecked virus spread.

  136. William Mackey says:

    Can someone mention an appropriate Zinc dosage for those of us cowboys taking responsibility for our own future?

    1. Fapnado says:

      Since people are discussing daily Zinc dosage – it MUST NOT BE above 150mg, since Zinc is highly toxic! Pay attention that you could get poised and die.

  137. Wendy P says:

    I love how everyone was so quick to call this guy a quack… when now data is showing that the death rate is HIGHER in people who were treated with hydroxychloroquine. I have to take it for my RA. RA is caused by an OVERACTIVE immune system. It’s already on overdrive to the point it looses control and attacks my own cells… hydroxychloroquine works by suppressing that overactive immune system. Y’all need to use your logic and connect the dots here that a suppressed immune system is compromised and faces greater challenges in fighting off anything, never mind a vicious, cytokine storm causing virus that leaves destruction in its wake in uncompromised immune systems. All he is asking for is supportable data instead of Craps or Russian Roulette to prevent harm. You know, like the harm of higher death rates in those treated with or using hydroxychloroquine. It’s actually quite simple and logical.

  138. Andrew Johnstone, RPh/MD says:

    Mechanistically it makes more sense to use the hydroxychloroquine EARLY, during the viral proliferation, and to use it WITH zinc (25-50mg for females, and 50-100mg for males due to prostate taking much of it up). The fact that it fails to help severely ill patients, especially if given without zinc, doesn’t disprove that it could help CV19 patients at all. Of course it doesn’t prove that, either – but I certainly wouldn’t use the referenced study, nor the one more recently from the VA, which suffered from the same flaws.

    In the later stages where the cytokine storm is the problem, I am so curious as to why there is no evident effort to reduce the PRODUCTION of those cytokines – only to block the receptors with antibody-drugs. Why not use something like low dose naltrexone, which reduces productdion of TNFa and IL-6, in conjunction with the ‘abcd’-imab of the day…? Or even something as basic as high doses of Omega-3’s…? Yes, those things “might affect other things” but when you have a 90% death rate for patients going on to ventilators, it is hard to justify insisting that be the “standard of care” one can’t add anything to without proving it will work splendidly.

  139. Andrew Johnstone says:

    The other thought is why use azithromycin with hydroxychloroquine, when they have additive cardiotoxicity as far as QT prolongation…? Why not add doxycycline to the HCQ instead…? It has similar ribosome-disrupting effects, yet is also a zinc facilitator.

    1. Forrest says:

      Perhaps because Zinc Sulfate can decrease the absorption of the tetracycline antibiotics, which includes doxycycline —

    2. Kirk Shrewsbury says:

      Someone has tried that and it worked. You can probably find it with a google search.

      1. Forrest says:

        This clinical trial should answer the question –

  140. Kirk Shrewsbury says:

    HCQ works in malaria by protecting hemoglobin, and I suspect something similar in COVID-19. The problem with waiting to use it only if the disease becomes very serious is that then it might be too late. The patient’s oxygenation is heading down toward zero, serum ferritin is through the roof, and the person’s hemoglobin supply has been ravaged. They will die from the equivalent of hypoxia, and HCQ will not reverse that. If it dies work by protecting hemoglobin, it must be given before most of the hemoglobin is harmed.

    1. theasdgamer says:


      Do you have a reference for your claim that HC protects hemoglobin?

  141. Kirk Shrewsbury says:

    This is an RNA virus. Can someone please explain to me why they don’t try reverse transcriptase inhibitors? They seem to work for HIV.

    1. drsnowboard says:

      Because RNA replication in COVID occurs through an RNA polymerase , not a reverse transcriptase. Wrong shaped spanner to throw.

  142. Karen says:

    First the author is not a Doctor. Second, not one mention of the results of trials using Zinc. You have to use Zinc along with HCQ.

  143. Cory Curtis says:

    Well Derek, you started a real poopoo storm here.
    The pros and cons each seem to have two things in common individually of each other.
    Cons two common denominators:
    1. They were already close to death
    2. They were being WAY overdosed (Hydroxychloroquine 600 mg a day, Azithromycin 500 – 250 mg)
    Pros two common denominators:
    1. Hydroxychloroquine 200mg dose
    2. and Zinc

  144. Jeremy says:

    “Chloroquine is a potent inhibitor of SARS coronavirus infection and spread”

    “Hydroxychloroquine Has about 90 Percent Chance of Helping COVID-19 Patients”

    1. Derek Lowe says:

      Keep in mind that the AAPS is not a reliable source.

      1. theasdgamer says:

        Oh, did AAPS push the Russia Collusion Hoax, the Jussie Smollett Hoax, or the Pee Dossier Hoax?

        Bathwater occurs everywhere. We each have to do our own due diligence.

  145. Jose says:

    Sorry for my poor english but I hope I can make myself understand.
    In France, the statistics of public hospitals that have followed the HCQ + AZM protocol, as soon as patients have been tested positive for PCR, have got a lethal rate divided by 2 compared to hospitals that have not used this therapeutic protocol. This protocol only works in the first phase of the disease. It no longer works in the second phase of the disease when the patient has pneumonia.
    These results triggered a parliamentary investigation to understand why the Ministry of Health had banned the sale of HCQ in pharmacies and advised hospitals not to use this protocol. In fact, no one in the department has been able to explain the good statistics of a protocol that officially ‘is not working’. None of the experts who advise the minister can explain why the hospitals that used it had half the deaths.

  146. albert can says:

    Interventional Cardiologist Dr Karl Poon outlines the classic triad of symptoms severe aortic stenosis patients may present with. He also describes the signs doctors should look out for in their patients, including heart sounds, blood pressure and pulse.

  147. ap setup says:

    Thanku so much for sharing

  148. When I am alone, I come to see your comments. It is a very good comment, how strange is your loneliness in this city, there are thousands of people but no one is like that. One is changed because you are not there, yesterday even the sunlight did not come on the wall. Thank you from my heart.

  149. peterboyce says:

    Your best knowledge and kindness in playing with all the pieces were very useful. I don’t know what I would have done if I had not encountered such a step like this.

  150. Androkim says:

    Thanks for posting

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