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Hydroxychloroquine Update, May 4

It’s been some days since I posted on the hydroxychloroquine situation versus the coronavirus epidemic, but I have been getting plenty of inquiries. So let’s have a look at what’s been going on!

Several people have pointed out this new preprint, a retrospective look at 568 patients in Wuhan. Update: there is something odd about this study. As pointed out below in the comments, the review board number quoted for it in the preprint is for a different-sounding study entirely, although with the same investigators and at the same institution. The Chinese Clinical Trial registry shows a study instead on the efficacy of an herbal medicine treatment (!), which raises the question of whether the “control” group here was being treated with that as standard of care. The preprint says nothing about this, and does not mention the herbal medicine manufacturer as a funding source, although the trial registry does. More details when and if they become available.

All of the patients were confirmed positive and on mechanical ventilation, median age 68, 63% male. 520 of them had standard of care (various antivirals and antibiotics), and in addition 48 patients were treated with 200mg hydroxychloroquine (b.i.d.) They measured hospital stay, mortality, and (interestingly) IL-6 levels as well. And their results were quite striking: mortality was 18.8% in the HCQ group and 45.8% in the others. That’s a much larger effect than anyone outside of Marseille has reported, I have to say. Patient IL-6 levels declined significantly in the treatment group, but not in the other cohort. The preprint’s Figure 3 also indicates that IL-6 went back up after hydroxychloroquine was discontinued.

That’s interesting indeed, and ties a possible mechanism of action to the same one that has led to HCQ’s use in rheumatoid arthritis and lupus: suppressing cytokine signaling in the immune response. This, however, runs against a lot of the theories advanced by the drug’s boosters. You’ll note that this mechanism has nothing to do with viral replication, for starters. And there is no azithromycin involved, as opposed to the Marseille protocol – in fact, I would expect Prof. Raoult there to denounce this paper for not following his recommendations (remember, his early results seemed to show that HCQ alone had some effect, but that HCQ plus azithromycin had a much greater one). There was also no zinc involved in this study, and if you’ve had the courage to look at the comments section here, you have been assured over and over that zinc is necessary for HCQ to have any effect and that people dosing without it are wasting their time. You will also find yourself being assured that it’s crucial to give HCQ as early as possible in the disease, and that studies that have shown no effect have failed because only severely ill patients were being treated. But this one has only patients on ventilators, in very bad shape indeed. In fact, if this IL-6 mechanism has something behind it, dosing early could be a bad idea – you probably don’t want to turn down cytokine signaling and immune response at first, just later on, when it gets to be a problem.

Thinking about that disease course question, some people have (very vocally) suggested that HCQ be given prophylactically, and a study testing this is underway in the UK. We have, though, a possible source of data already, that is, the many RA and lupus patients who have already been taking the drug. One of the features of my emails has been a reference to this report in the Italian press (near the end of the article) that the Italian Rheumatological Society (SIR) has been collecting data on just this question from 1,200 physicians there. The article says that there are 65,000 patients in Italy taking HCQ chronically and that only 20 of them have tested positive for the virus. Now, you’d want to compare that to RA and lupus patients who were not taking HCQ, but it would still be quite interesting. If it were true.

But I can’t see where that figure comes from. That one Italian press report is the source that everyone else refers back to. And when I look at the SIR itself, I find that it is part of the COVID-19 Global Rheumatology Alliance, a worldwide data collection consortium. Their worldwide provider-entered database of coronavirus-positive patients says that it’s up to 1072 cases (on the front page) and 777 of those have data broken down into categories here. According to this map, 84 of these patients are in Italy (not 20 as stated in the article). The provider registry is just of people reported by physicians, and it shows that 24% of those 777 patients (188 of them) were taking antimalarials such as HCQ when they tested positive for the virus, so if that percentage holds up, then there are indeed about 21 Italian rheumatology patients taking HCQ that have have tested positive and been reported on in detail by their physicians. But as for those 65,000 Italians who are taking HCQ, I can find no evidence of that at all, and I have no idea how many of the Italian HCQ patients are being so monitored. The 65,000 number may well be coming from Italian researcher Annabella Chiusolo, interviewed here at the Jerusalem Post, but the worldwide patient survey numbers at the Rheumatology Alliance are only 11,762. The most recent breakdown of those numbers look at 9,541 patient responses, with about 28% of them were taking antimalarials, and a total of 465 coronavirus cases.

Update: here’s the answer. The number is completely fictional. As mentioned here in the comments, the president of the Italian Rheumatology Society was contacted directly and states that this number is completely wrong, that the society is monitoring 150 patients in its registry, 20 of whom are taking hydroxychloroquine. The 65,000 number is bogus.

That’s not the only new hydroxychloroquine-related preprint out there, although it’s certainly the one that people have been sending me. Here’s another from the Cleveland Clinic-Abu Dhabi (didn’t realize that they were over there) with another retrospective study looking at viral clearance in HCQ-treated coronavirus patients. It’s a small study, but out of 34 positive patients, the 21 treated with HCQ had significantly delayed viral clearance compared to those received other standard of care. If the early hydroxychloroquine studies had shown numbers like these we probably wouldn’t have heard much more about it, to be honest, although with such small patient groups one result is probably as nearly likely as the other. And here is a joint preprint from NYU and the University of Milan on the hydroxychloroquine/azithromycin combination specifically, a retrospective study of 251 patients on that regimen who were monitored by ECG. QT prolongation is of course the worry here, and it was certainly picked up in an exposure-responsive manner, with 16% of the patients showing clearly dangerous levels. Overall, the cohort did not completely return to normal after HCQ/AZ dosing ceased, either, and the paper concludes that the efficacy of the drug combination remains unproven but that the risks seem much more clear. Similarly, this team from Cedars-Sinai in Los Angeles reports analysis of a series of 490 positive cases, who received no HCQ, HCQ alone, and HCQ-azithromycin, mostly that last combination. QT prolongation was again noted, with 12% showing dangerous levels and with a trend towards being most prolonged on the combination (especially when compared with azithromycin without HCQ). Interestingly the cardiac effects were noted only in men – I haven’t seen anyone else mentioning that. This group also concludes that the benefits of this treatment are unclear but the risks are much easier to quantify, and urge caution.

So overall we have one positive report (very positive indeed, and an outlier in that respect) and two safety warnings. Make of this what you will. We have more controlled trial data coming, and the arguing can re-commence when it hits. . .

248 comments on “Hydroxychloroquine Update, May 4”

  1. metalomaniac says:

    The Wuhan water supply must have high levels of zinc…

    1. garcol says:


    2. “inhibit the virus from reproducing or infecting other cells in a test tube. Within a week the highly regarded journal Cell Research published a PEER-REVIEWED letter by researchers at the Wuhan Institute of Virology that reported on two of these in more detail: chloroquine”

      1. Mark McNulty says:

        Why is everyone so obsessed with peer-review? I’m afraid it’s become a fallacious backhanded appeal to consensus. Don’t you realize that peer-review is not the same thing as independently reproduced results? Peer-review is nothing more than glorified proofreading and in fact, before about 1970 peer-review wasn’t even done formally. Was all science bunk before 1970 due to the lack of peer-review? I don’t think so.

        1. Lester Kobzik says:

          imperfect, agreed….but better than nothing, and generally a useful screen for interested parties who can only read/analyze a limited fraction of the torrent of papers published….

        2. metalomaniac says:

          I’m not obsessed. I just think that it helps to weed out the junk, so long as the peer cadre are credible.

          BTW, zinc is my sacrificial anode!!! 😉

          1. loupgarous says:

            A beverage warning for those of us typing on nonreplaceable keyboards, huh? 🙂

            And yeah, peer review, like reports of clinical results themselves, is an imperfect tool but necessary.
            Retraction Watch, I find, is a good resource for when peer reviews themselves don’t pass the smell test.

  2. Stat Reck says:

    Very frustrating that the only mention of exposure-response is for safety.

    “Don’t tell me what to use without telling me how to use it.”
    – Every doctor, ever

    1. Michael Mantion says:

      you can tell me what to do, or how to do it, but not both.

      Every intelligent person ever.

      1. Stat Reck says:

        Well, cute but wrong, at least in this case. The regimen is everything in drug development, and your statement equates to saying, “I refuse to listen to what you have to say.”

        Which is inconsistent with taking an evidence-base approached to things.

    2. Harvard Medicine, Kaiser Health: Growing number of reports now say coronaflu itself causes heart damage and arrhythmias, possibly due to lack of oxygen

      1. Jeremy says:

        As someone who suffers from sleep apena before it was controlled it absolutely did damage to my heart. The low oxygen levels can be disastrous to the body/organs.

  3. IneedToGetOutMore says:

    In before
    “Zinc Ionospore!! Ya gotta start it right away, like before they get a virus test! Use, like, a truckload, don’t be such wimps!!
    People, just let me handle this, I’ll get it knocked out STAT! “

    Einstein didn’t count on the internet magnifying human stupidity.

  4. blogreader01 says:

    Who the hell is the AAPS and where do they get off implying that the Governor of AZ has erred by issuing an Executive Order forbidding prophylactic use of chloroquine (CQ) or hydroxychloroquine (HCQ) unless peer-reviewed evidence becomes available?

    1. Oblarg says:

      AAPS is a known quack organization.

      1. theasdgamer says:

        Weak minds base their decisions about data on the reputation of the author. A thoughtful person who has critical thinking skills will consider the data and filter the baby from the bathwater.

    2. Derek Lowe says:

      Recommendations from the AAPS do not sway me much, despite their impressively official-sounding name. They hold a number of positions that I regard as fundamentally unsound.

    3. “inhibit the virus from reproducing or infecting other cells in a test tube. Within a week the highly regarded journal Cell Research published a PEER-REVIEWED letter by researchers at the Wuhan Institute of Virology that reported on two of these in more detail: chloroquine”

  5. blogreader01 says:

    Moreover, everyone with a lick of sense knows that HCQ is pure snake oil being nefariously hyped by that Trump guy (i.e., the huckster who had the audacity to beat our wonderful Hillary in the last election). It’s a crime against humanity, I tell you…

    1. loupgarous says:

      Where’s DJT’s medical degree? Oh, DAMN. He doesn’t have one. After residency, he can join the debate over how to treat this virus.

      1. Jon Doe says:

        Trump’s medical doctorate is in the same place as that of Billy Gates, the high school dropout who is a (computer) virus expert, who makes billions from pushing vaccines.

        1. Some idiot says:

          How does he do that exactly? I know he donates money to vaccines research, but I am not aware that he makes money from them…?

          1. Beebee says:

            He owns patents on the on a previously coronavirus vaccine, for some reason. To produce this vaccine, you will have to buy the contract from Gates.

          2. Some idiot says:

            Do you have a (reputable) source for that? Incidentally, if that is true, then he is not earning money on it, because there _are_ no commercial Coronavirus vaccines…!

        1. Some idiot says:

          Do you have a reputable source for that?

          1. Lester Kobzik says:


            According to this, the incorrect idea that Gates has a patent on otential coronavirus may be linked to the fact that the Pirbright Institute in the UK (recipient of 2 Gates foundation grants) has one but for chickens only!
            “While the institute does hold a patent for a coronavirus that primarily affects chickens, it does not hold a patent on any part of the novel coronavirus causing the current COVID-19 pandemic.”

          2. Some idiot says:

            Ah, thanks Lester! Always nice to see where the whole thing grew/ was spun from…!


    2. Charles H. says:

      Well, I’m less likely to believe something if Trump proclaims it, but that doesn’t mean he’s *always* wrong.

    3. chuck says:

      You are a blatant Moron, for stating something like that about Clinton,,,,,imagine what would be going on right now in this country if that filthy lying witch was elected,,,,you evidently have no comprehension skills, or all you follow for your information is MSNBC and CNN……people like you are Disgusting to Normal American’s

      1. Bill says:

        You seem nice. How about we focus on the administration that actually exists and its actions? For whatever reason, there seems to have been a lot of irresponsible hyping of HCQ. And the evidence remains mixed to negative for its efficacy.

        1. Jayne says:

          Here’s a thought. How about if you get the virus, then you don’t have to take HCQ.

          This INSANE opposition to it – especially by millions of people who don’t have a clue what they’re talking about and are driven exclusively by their hatred of Trump – needs to end.

          Let people who think the quite definitive study from the French epidemiologist (who is highly regarded whether Fauci recognizes it or not) showing HCQ + AZ to be over 90% effective as well worth the risk.

          I find it fascinating that it’s the same crowd who’s perpetually screamed that it’s a woman’s choice to abort her baby are the same one screaming now that people can’t take the antiviral they want to take when they’re sick or to keep them from becoming sick.

          You people need help. And I promise you that someday you’ll realize it’s YOU who has been duped. The drug really does work. And at this point you appear to be cheering for deaths.

      2. loupgarous says:

        blogreader01 was very probably being sarcastic.

        1. drsnowboard says:

          blogreader01 was probably being sarcastic, but chuck ? Not getting that vibe, maybe It’s tHe CaPitaLs…
          I don’t doubt that China wanted to cover up the initial outbreak, but the really scary aspects of this pandemic is the swirl of nonsensical conspiracy theories it has generated (5G spread, Gates Illuminati rebalancing, HCQ suppression etc) , the deep deep mistrust of the federal government, the long loud dog whistle now being blown by the Trump administration to mobilise public opinion against China as an outside actor to be attacked. Where does this deep seated paranoia come from? Is it the realisation that China has been the manufacturing power in the world for the last 10 years? Strikes me we are in danger of reversing into the Dark ages, via McCarthyism etc and …etc.

          1. loupgarous says:

            Doc, you’re generalizing about 330,000,000 people based on Chuck and a few people like him. It’s not a good look.

            As far as Chuck’s statements, they started not with distrust of the Federal government but of a single politician (although voiced in a massive non sequitur). You don’t seem moved that deeply when someone prangs Trump here. The fictional detective Harry Callahan summed up my feelings about political opinions here. It’s a med-chem blog, not

      3. Beekeep says:

        Yes! She would have just said (referring to the thousands of lives lost), “What difference does it make!”

      4. Beth says:

        “Person. Woman. Man. Camera. TV.”

    4. Jack says:

      You’re a scientist. Politics should not enter into your mind with regard to any drug or treatment. Objectivity is paramount. Yes, DJT is absolutely wrong about HCQ. I am a Republican (not a support of DJT) and the lack of objectivity from both sides of the aisle is absurd and dangerous.
      This needs to end and it needs to end now. Take a deep breath and divorce yourself of your “feelings” and examine the evidence with an impartial mind or suffer the same fate as scientists and physicians throughout history. Just moronic.

    5. Crash Brown says:

      I flew back from London in late February to New York, and then flew New York to San Francisco. Two of the flight crew and myself were probably the only Caucasians on board. Everyone else was Asian. Everyone was coughing, hacking, gacking, and snotting the whole flight. I was fine for about two weeks, then Bam!!! No smelling, no taste, headaches, joint pain and 103.4 temperature. I fought hard for every breath in the hospital for two and a half days. They didn’t want to put me on a ventilator and kept encouraging me to get through another hour, then another hour, and another hour. My family doctor came in and gave me 500 mg of HCQ. In two hours my fever broke, and my oxygen levels begin to rise. I continued taking it for five days. It works. Sickest I have ever been in 64 years of my life.

      1. Derek Lowe says:

        Glad to hear you’re better, but 1 dose of HCQ as a cure is something that you couldn’t even convince Didier Raoult of. . .

        1. OC says:

          Pretty sure he clearly said he took the drug for another 5 days.

          1. loupgarous says:

            Crash Brown (after an asian-phobic intro):

            “My family doctor came in and gave me 500 mg of HCQ. In two hours my fever broke, and my oxygen levels begin to rise.”


            That seemed to me to indicate a one-dose cure followed by five days of continued medication. Usually medications require a certain level of medication to be present in the target organs before symptoms of the disease go away.

            Have to agree with Derek here. This is a clumsy troll promoting HCQ with a story that doesn’t jibe with descriptions of its activity in actual clinical trials.

          2. theasdgamer says:

            500 mg of HC is a VERY large dose. Don’t know what his zinc levels were–if he had been on prostate supplements and Men 50+ vitamins, his zinc levels might have been high, too.

            It’s an interesting story. Not something to dismiss out of hand.

      2. Jeremy says:

        Glad to hear you recovered well. Thanks for sharing.

      3. alvin hunter says:

        I am so happy you are better. But here is the thing.You would be around the 35th patient that has the same story.
        Patient 1: had it for 35 days (took a test at a doctor each and every week, only told positive.
        Took hydroxy (200 mg) and the z-pak. Hands started sweating after a few hours. Then not no more than 5 days later, tested virus free…finally.

        patient 2: had it for 7 days and was just about to be intubated (oxygen level below 90%)
        took hydroxy
        about 8 hours later, oxygen level went back to 98%, and can breathe again. Viral free after 10 days, Took a little longer than usual.

        Patient 3:
        Had it for about 12 days, about to be intubated. Was given a chance to take hydroxy. Took it.
        about 7 – 8 hours later, was feeling better, can breathe again, didn’t have to go on oxygen. Was virus free after 8 days.

        Patient 4 -5 and 6 (family): loss of smell, can’t breathe, also about to go on intubation.
        took hydroxy:
        8 hours later, feels better, can breath.
        The next day, taste and smell comes back.
        appetite returns around day 3.

        now I’ll go on a story about a non treated patient (a dr. for that matter)
        20 days with virus, loss of smell, taste. Almost burned food badly, because couldn’t smell at all around day 12.
        Can barely smell garlic in front of her nose <supposive recovery)
        Barely getting better day by day, but it's taking a while.
        can breathe again luckily.
        she's hoping her senses come back.

        Now….I don't know about you guys, But to me, something has to be working. Anecdotal or not, there are more stories like this all over the web. I can provide proof, but most are youtube videos and no one likes youtube vids, so I'll just post it in text form.

        Glad to see you are better!

        1. JP Leonard says:

          Yes there are good stories like that – but physicians please take the time to quantify results with N of 1 trials, otherwise it’s just hot air blowing against a cold wind. See http://fieldtrials.net

        2. Steingrimur Hermannsson says:

          My wife, myself and two neighbors were treated for CoV 19 with HCQ/AZM/zinc. Fever normalized and breathing improved for all of us withing 1 day of starting this protocol. All clear in under 10 days. HCQ has been used clinically for 65 years. The total cost of medication for treatment is less than $50. Remdesivir costs $1,000, has 25% serious side effects, requires IV, and shows very little improvement in mortality. Let your doctor treat you without the outside influence of others that may not have your interests in mind. Your doctor can apply his/her clinical judgement to treat you – without outside interference.

          1. Gareth torney says:

            Agree 100 percent.

          2. This says:

            What doses did you use ?

    6. Wallace Grommet says:

      HCQ, believe me, great stuff! You know what’s better? I just thought of this-check it out! A big UV lamp up your keister, while you chug some BAC solution! It’s like a miracle! One minute later you’re cured!

      1. JP Leonard says:

        tiresome puerile yukking it up – be serious for once

    7. RUI GASPAR says:

      blogreader01, you appear to suffer from TURDS. Thankfully there is a cure, it’s called November 3rd, 2020. lol

  6. Tom Boyer says:

    The QT prolongation is a red herring that keeps getting waved by people who don’t want to listen to evidence that this drug might be saving a lot of lives. And a lot of these people have a paycheck in the outcome unfortunately.

    Imagine if someone found that acetaminophen worked against covid and the response from the medical/hospital establishment was a collective hue and cry:

    “We’re shocked, SHOCKED to find out that acetaminophen is highly toxic to the human liver if given in massive doses to very sick people! So let’s stop the studies, ban Tylenol, and instead look at that experimental medicine that costs $1000 per dose and can only be administered in hospitals!”

    Efficacy is the question with HCQ. If it works, the safety risks are manageable like they are with most approved drugs.

    And let’s openly acknowledge that if HCQ works, it will be highly toxic to some people’s revenue outlook.

    1. Cys says:

      not unlikely that acetaminophen works: its toxic metabolite is a thiophilic molecule which can also block the reactive Cysteine in the active site of the Cov Cys protease. So if you feel a bit of Covid-19 coming up a man can take 4gr/day and woman 3gr/day for a week without liver damage and much fewer people moving into the hospital

    2. David Young MD says:

      I am not worried about QT prolongation. People with Rheumatoid arthritis or Lupus take Hydroxychloroquine all the time and don’t worry about QT prolongation. I very much doubt that none of them get EKG’s done before prescribing Hydroxychloroquine. That is, of course, for the usual 200 mg twice a day dose. They take it day after day for years without problems.

      I think that it is totally unfair that you bring up the cost aspect of it. No physician would ever consider Remdesivir over Hydroxychloroquine because they would make more money with Remdesivir. If Hydroxychloroquine works, then that would be a huge savings to our health system.

      Or… maybe both drugs together would work the best… who knows.

      The Chinese data is interesting and sure makes one want to reconsider Hydroxychloroquine. It was not mentioned above that the study was randomized, though. I am not certain that it was and if not… well, then it doesn’t have the strength that it would have. It is certainly possible that those patients who were not that ill in the first place were preferentially given Hydroxychloroquine.

      Time will tell. There are a few randomized, blinded studies going on now.

      You might not be aware of how insurance pays hospitals. It is not on the basis of the costs incurred by the hospitals. Medicare does not pay a hospital more money because they use Remdesivir rather that Hydroxychloroquine. Instead, a hospital would make far more money by using the cheaper medication.

      1. Roach MD says:

        Agree. Keep the profit mongering accusations for the industry and policy makers and away from we frontliners.

      2. David says:

        “People with Rheumatoid arthritis or Lupus take Hydroxychloroquine all the time and don’t worry about QT prolongation.”

        However, coronavirus seems to cause myocardial inflammation, which increases susceptibility to arrhythmia. So HCQ could be more dangerous in that population.

        1. David Young MD says:

          You have a point

        2. Emmanuel Ohannessian says:

          Does myocardial inflammation start at the onset of Covid-19? The doctors who are having success with HCQ are advocating taking it early for the treatment.

        3. theasdgamer says:

          Since covid can potentially damage the heart more as infection continues, a judgment has to be made as to whether the risk from treating with HC is greater for the patient than merely giving supportive care. It may vary from patient to patient.

      3. Karen Collins says:

        My thoughts exactly, thank you for your post!

    3. David says:

      Acetaminophen has been proven effective in multiple rigorous trials. The toxicity is very uncommon for dosing < 3-4gm/day in otherwise healthy adults. These aspects of its use are well understood.

      There is scant, even contradictory, evidence that HCQ works in coronavirus infection, and there is considerable evidence of risk that is not well understood (note that efficacy requires a higher burden of evidence than does toxicity).

      I have no financial stake in this, and also I profoundly want to find a drug, or drugs, that have favorable risk/benefit ratio. But I also don't want to negligently recommend a treatment that may not work, or may work to only a minimal degree. I don't want to push out treatments without understanding the dosing regimen (which may be different for different stages of the illness). And I don't want to cause net harm by pushing a drug whose cardiac risks may outweigh its benefits, if those benefits are marginal.

      We simply don't know enough now to make an ethical recommendation outside the setting of a clinical trial. My final point: continuing to expose patients to treatment in improper or potentially invalid trials will only generate more confusion and is itself unethical. GCP 2.5: "Clinical trials should be scientifically sound".

      1. Mark B Smith says:

        That’s the other issue, however. It’s one of time, which requires battlefield medicine. By all means, do the clinical trials on hydroxychloraquine-azithromycine-zinc in a leisurely fashion. But if in the meantime, given that NOTHING ELSE IS OFFERED by the medical community, and my risks of exposure keep escalating, and I’m old and sick, give me the medication.

        1. Taileen Alvarez says:

          I am curious if there’s a possible correlation between ADRA2b gene known as the “highly sensitive person” gene and auto immune diseases such as ITP or hypothyroidism. Maybe even cancer and HIV ( I am not a scientist or doctor in any way) just wonder if there can be some connection.)

        2. loupgarous says:

          I”m old, a survivor both of cancer and chemo/radiation. I’m fighting diabetes and have narrowing of the coronary arteries visible on X-ray. There’s no way I’m taking HCQ, because the evidence indicates it’ll just make me more liable to injury of the heart and pulmonary blood vessels if I do contract SARS_CoV2 or any of its mutants making the rounds. I’m in contact with my doctors via Internet and phone and the specific advice I’ve had re: COVID is “isolate and keep the blood sugar down”. One of them recommended Tylenol for the cold-like symptoms I’ve had which don’t add up to COVID.

          Islolation both by space and personal protective gear has been working for me and my wife so far. We are supplementing our diets with zinc and three known ionophores which don’t have the toxicity issues of the quinine derivatives, and vitamins which help with lowering blood sugar. If I get COVID, I’ll follow competent medical advice. That could include a Z-pak (azithromycin’s worked for bad sinus infections before for me) but no malaria cures, thanks.

          1. Mark says:

            Excellent solution to your issue

    4. Nick says:

      Agree and by giving K+ you can decrease the chance of QT prolongation.
      Can also use Quercetine and Green Tea extract as OTC zinc ionophore.

      New data showing there is epithelium inflammation causing strokes , heart attack and blood clots. OTC supplement that could help SOD , Glutathione , Zn,Cu,Mn,Fe , Vit C , Vit D3 , Vit K2(MK7&MK4)

        1. Nell says:

          Zinc ionophores including quercetin and valproic acid failed to inhibit coronavirus in vitro. It appears that the mechanism of action of hydroxychloroquine is something other than zinc.

          1. Nick says:

            Thank you for the link . I did not see where it stated that.

          2. matt says:

            To Nick, didn’t read the text, but Supplemental Table 6, lines 6 and 66 (hmm at the 6s…), columns M and N might be some of the results he was referring to? No NYC viral inhibition of valproic acid and quercetin?

          3. Michael Bell says:

            Or perhaps, we’re approaching this illness from the wrong angle. Perhaps the reason why HCQ has some efficacy is due to the fact that we’re missing the actual target of the virus itself. While the virus is definitively a respiratory virus, suppose that in people with certain blood types, especially ones of the Rh negative variety, the virus also induces a blockade on hemoglobin, thus reducing the total hemoglobin and as a consequence inducing hypoxia. This would explain why the virus has such a wide range of presentations. HCQ might be freeing up the hemoglobin.

          4. Richard Lansink says:

            Where does this research state that, please ?

          5. Nick says:

            It was theory only and relatively safe.
            I have read Iodine ( PV-I) kills virus few seconds.
            They make a nasal spray in Japan.
            The study stated concentration required to kill the Corona-virus.
            Iodine can stain and should not use if you have thyroid issues with medical supervision.
            Some practitioners using nebulized PV-I straight to the lungs – I don’t know at what concentration.
            Again putting things together – theory only no control double blind.
            All this to kill the virus before the cytokine storm starts.

    5. Jayne says:

      BINGO. You are precisely right.

  7. JP Ladislaw says:

    Thanks for the update. I wonder if you had to create a set of criteria for prioritising drug candidates to repurpose in a pandemic situation, what they would be, and whether HCQ would come close to the top of the list. Surely things like clean safety profile, clear mechanistic rationale, consistent early efficacy signals would be in that set of criteria? Yet contradicting results like this show how extraordinarily nuanced everything in drug development is and how such criteria might be self-defeating (E.g. works well in later stages, not early stages, at X dose, in Y patients etc). I wonder how you could go about this more systematically without missing potential gems…

  8. Some idiot says:

    Marginally (but only just…) off-topic, the Australian Army is starting a trial for prophylactic use of CQ (not HCQ). I don’t have much info on it, but so far there have been 42 volunteers. It will be a 14 week trial. Dosage 300 mg CQ/dag for 3 days, followed by a “weekly dose” of 300 mg CQ, for 9 weeks. What they are doing with the other weeks, I don’t know… And I don’t know whether to not they will be deliberately exposed to the virus or not. However, there were apparently some ethics issues which raised eyebrows, but apparently the whole study has now been approved.

    That’s all the info I have on it…

    1. Sunyilo says:

      I’m seconding the emphasis on different dose regimens. Chronic use of CQ/HCQ as far as I know, is 300mg weekly. The commonly reported regimen for COVID-19 treatment is 400mg daily (or 200mg b.i.d.) which – knowing the extreme long clearance of this drug and its metabolites – results in dangerously high Cmax for this regimen and hence brings out the worst of the side effects.
      For any further discussions the dosage should not be left out (probably a lot more important than AZT +/- or Zn +/-)

      1. Robert Clark says:

        That 300 mg weekly is for the antimalarial action. In contrast for lupus 400 mg daily in two doses is common.

        Robert Clark

        1. Some idiot says:

          Ah, thanks… that makes a bit more sense then… (-:

    2. intercostal says:

      I would think you’d need a *lot* of volunteers, since an army is probably composed of mostly relatively-young and relatively-healthy people. Unless they are testing whether it reduces the % positive, not % developing serious symptoms, hospitalization, death etc.

      The USS Theodore Roosevelt has had over 1,000 infected and I don’t think more than 7 or so were ever in the hospital at one time, with 1 death (so far at least). So I would think you’d need a huge population to see a statistically-significant difference in effects: if you have 1,000 people infected, half of whom are taking HCQ and half aren’t, if you see 4 hospitalizations in the 500 with-HCQ and 5 hospitalizations in the 500 without-HCQ, what does that tell you?

      1. loupgarous says:

        Without using statistical tools, one can do case fatality comparisons for each arm and say it’s a 20% reduction of deaths for HCQ. But we apply statistical tests to numbers like these to make sure we’re understanding ths significance of the results. I won’t even try, it’s been years and I don’t have access to SAS now. Just saying,

        1. Statistical tests are legitimate only when they are specified before you’ve looked at the data. Still, it’s not silly to wonder how a placebo A-versus placebo B trial with 9 total events is likely to come out. The binomial distribution says that you’d see 9B/0A about 0.2% of the time, 8B/1A about 2% of the time, 7B/2A about 7%, 6B/3A about 16%, 5B/4A about 25%, and similarly down the other side.

  9. Real World Evidence with AI can deliver results faster than clinical trials, and we are starting an individual patient data consortium, details:

    1. Robert Clark says:

      Thanks for that link, Mr. Benhenda. I’m engaged in a similar project to review collected patient records to find which medicines are most effective:

      Big Data to fight COVID-19 and Other Diseases, Page 2.

      Perhaps we could collaborate?

      Robert Clark

    2. Vijay Gupta says:

      Wonderful. A ML/AI mindset/methodology has the flexibility to adapt to the ever changing information on this situation. For example. the Global Solidarity Trials (RCT) by WHO may be obsolete as the understanding of the phases and nature of the disease has changed in the past weeks.

  10. Jack Ryan says:

    Studies have shown the hydroxychloroquine is used to prevent/alleviate blood clotting in individuals. A study has also shown hydroxychloroquine use is associated with a 73% less risk of developing cardiovascular disease.

    Reports now suggest that some of COVID’s affects are the clotting of the blood and strokes. Is this another (unrecognized) mechanism for why many doctors believe it works?

    1. David Young MD says:

      Well, Hydroxychloroquine is not used in the clinic to prevent bleeding or to prevent clotting. As a hematologist for the past 35 years, I think I would have run across that. Those who use it, use Hydroxychloroquine as an anti-inflammatory, particularly in the setting of rheumatoid arthritis or lupus.

      People get clots and/or bleeding with Covid19 as part of a general consumption of clotting factors, a condition known as disseminated intravascular coagulation. This condition may be seen in bacterial sepsis. or a gangrenous limb among other things. The sort of DIC seen in Covid19 patients is particularly bad from what I hear and may have other processes involved to make it bad.

      Most DIC is untreatable, other than… “treat the underlying disease”. I really don’t think that Hydroxychloroquine would have an salutatory effects on DIC. It is certainly never used in DIC from other causes.

        1. Kaz777 says:

          Very interesting. Thank you for posting these.

        2. rtah100 says:

          The two papers were very interesting, thank you. It made me wonder about the role of CQ in the NO system and, lo and behold, CQ has been studied as a promoter of NO synthesis.

          There is something very interesting going on the CQ and late-stage COVID blood disorders (clotting, ferritin) as well as with the immune response. It is thought to modulate NO synthesis by reducing free Fe concentration and to reach effective levels in epithelial tissue very rapidly because of its volume of distribution.

          “The chloroquine effect was dose dependent, and reached its maximum value at 20 mM. This concentration is from 2- to 10-fold higher than that measured in serum with the regimens used to treat rheumatoid disease (23, 42) or achieved in plasma of malaria patients during intravenous infusion (43) and intramuscular administration (44), but it is very likely to be reached and overcome in endothelial cells lining the vessel wall. Indeed, the drug accumulates thousands-fold in the intracellular acid compartments within few minutes, due to its weak base properties (23), and this leads to a very high gradient of chloroquine through the cell membrane.”

        3. matt says:

          Wait, did you connect antiphospholipid syndrome (APS) to Covid-19 somehow? Are there other papers suggesting the reason patients see clotting in Covid-19 is due to APS? Or was this just a search for anything related to HCQ?

      1. MD Forte says:

        I work with autoimmune/immunological and use quite a lot of hydroxychloroquine, biologics etc.

        There is a unkown/”x-factor” to what HCQ actually does. Normal dose is actually usually 200 mg pr day few need 200 mg x 2 and retinal deposits are much less frequent.

        Anyway maybe we will never know or understand exactly how hydroxychloroquine works, but if it reduce IL-6 and probably other cytokines in the cytokine soup/storm, then if given at the rigth time then it could perhaps avert DIC or need for respirator. As it seems like the virus does not kill on its but by leading the immunesystem in wrong/excessive directon/response.

        If you see the common symptoms headache, lethargy, myalgia they are very indicative of excess pro-inflammatory cytokines.

        Dosage HCQ, too me 200 mg x 3 pr day seems a bit high, 200 x 2 is usually enough. But if already in ICU on a respirator, this seems like worth while risk to take by now. Remdesivir does not have any such data so I would choose HCQ, plus pitivastatin (a potential main protease inhibitor), telmisartan and perhaps a tetracycline instead of azitromycin, doxycycline or minocycline. And hopefully access to monoclonal antibody IL-6 if needed.

        I also do not think double blind RCT is ethical in ICU setting and would not opt to get “sugar-pills” in that case. I think RCT are ok for prohylaxis/vaccines to avoid bias but not as rescue therapy.

      2. Sam says:

        My apology for asking about inflammatory diseases instead of Covid. There’s not a lot of info out there to research my question. I’m am curious to know if people with Rheumatoid Arthritis/Lupus that are prescribed HCQ are also prescribed Zinc to help it work better. Does it help with absorption or assist in working together to compliment a disease that is debilitating and carries with it a lot of terrible pain and suffering. Thank you folks.

  11. NMH says:

    …or maybe you can’t trust any kind of “scientific research”, or anything that could get published in a prestigious (or not prestigious) journal, from China:

    Its absolutely asinine to believe any research from that country.

    1. Smut Clyde says:

      As the author of that piece, I am flattered, but I certainly don’t go as far as advising people to ignore all research in China.

    2. Vijay Gupta says:

      Medical authorities and researchers in the US, Canada, UK, France, Brazil and some other western nations should swallow their pride, reassess the reliability of research by universities like Stanford & Columbia (and the review of such studies by the NIH), and realize that they have wasted weeks. Feb 19 2020- Chinese research published on microclots, cytokines, ferritin, and other blood abnormalities. By end of Feb 2020, more research published on phospholids. Success of HCQ in China and South Korea. Research on benefits of masks in Japan. For weeks, most western nations have been winging it, rediscovering aspects already reported in Asia. After the NEJM and VA studies, work so shoddy that even a non-medical person like myself could shoot down (I know stats), many will not trust the Ivy league, Stanford, NIH, CDC, FDA… A collosal change in perception on American medical research and regulation.

  12. Jack Ryan says:

    At this point, are control groups being given placebo’s really necessary? If information was pooled, we should have enough data with respect to how people fare without a particular drug that is being tested.

    1. Churlish says:

      I would say “yes”, as we’re clearly still trying to figure out if HCQ shows efficacy against COVID19.

    2. loupgarous says:

      We need as many placebo studies as possible, randomized and blinded, to rule out investigator bias and to add to the clinical database on the toxicity of HCQ as prescribed for COVID-19. Without them, it’s all assertions and anecdotes, not evidence-based medicine.

      1. Some idiot says:


        1. PhillyPharmaBoy says:

          Be cautious of the information contained within the link above. It comes from a right-wing group, the Association of American Physicians and Surgeons, that is less of a medical organization than an anti-government lobby. It opposes Medicare, Medicaid, abortion, gun control and vaccinations. The “peer review” summary of the efficacy of hydroxychloroquine against COVID-19 is biased and incomplete, with negative studies missing.

    3. Rob says:

      Without a control group and randomization, you run the risk that you have unwittingly selected a group of patients that would have done better even without the medicine. Pooling studies and more data just gives you a bigger biased result.

  13. Jack Ryan says:

    New preprint on the positive effects of chloroquine on COVID-19:

  14. Robert Clark says:

    Since this is a retrospective study the argument can be made that the sicker patients were the ones that got HCQ, as with happened with the VA study.

    For instance some of the patients in this study had pneumonia which is an indication of severe disease. What was the proportion of those that got the HCQ?

    Robert Clark

  15. Christophe Verlinde says:

    I performed a Google Scholar study with as search terms “Dao Wen Wang” and “Tongji hospital”, the corresponding author of the Chinese study and his/her location, limiting the results to publications in 2020. Result: 19 papers, almost all of them in the field of cardiology, not surprising as the HOCQ paper lists Department of Cardiology as affiliation.
    A few questions arise. Why did a cardiologist run the trial? How is it possible that someone who runs a trial in the midst of a crushing epidemic publishes at the same time papers at a rate 5/month? I don’t know the answers to these questions, but I would be glad to learn.

    1. Adrian says:

      He is a professor at a university hospital, why are you surprised when many papers written by people researching under him list him as co-author?

      They were not looking for antiviral effects in a respiratory disease like the crazy French. They were hoping for the suppressing of cytokine signaling in the immune response that would be logical for the standard lupus medication. Cardiovascular internal medicine is the correct area for that.

      1. Christophe Verlinde says:

        Not a co-author but the corresponding author!

        1. An Old Chemist says:

          In Asian countries, the scientist in-charge of the institute gets his name as the corresponding author on all (or most) of the papers coming out of that institute. Often times, this person is also the one whose research grant is funding most of the research. And most of all, this person is a career maker for everyone in the institute, and everyone wants to keep him happy!

          1. matt says:

            Apparently this is a practice in some French countries, too.

  16. Daniel Barkalow says:

    It would be ironic in just the way that medicine is usually ironic if it turned out the HCQ was slightly counterproductive against coronavirus, but worked great against autoimmune complications from it. Like, an autoimmune drug works against an autoimmune disorder, and it’s coincidence that people were trying to use it as an antiviral before they identified an autoimmune component to the syndrome.

  17. Robert Clark says:

    That retrospective study I was referring to was the one Mr. Lowe mentioned from the Cleveland Clinic-Abu Dhabi:

    Hydroxychloroquine is associated with slower viral clearance in clinical COVID-19 patients with mild to moderate disease: A retrospective study.

    On page 7 it says there was no significant difference in pneumonia between the HCQ and non-HCQ groups. But when I looked at the data on page 19 I was surprised and dismayed to see the number of pneumonia cases for the HCQ group was 11, or 47.8%, but for the non-HCQ group only 3, or 27.3%. It is unreasonable to take that as an insignificant difference when it is known pneumonia is an indicator of severe illness.

    A key question I would like to see answered is whether or not the PCR assay for virus is able to do counts, or is it only a yea or nay? If it is able to do counts then the more severe cases such as those with pneumonia would be expected to have higher counts. Then it would be expected to take longer to get viral clearance in those cases.

    Robert Clark

    1. intercostal says:

      Maybe this is a case where “insignificant” means only “lacking statistical significance” (which can be due only to small sample size) not necessarily “unimportant”?

    2. x says:

      It appears they’re using real time PCR, so yes, they can quantitate viral load if the test is set up to capture that info.

      1. Robert Clark says:

        Thanks for that. In this report and in Dr. Raoult’s work, they use viral clearance as indication of cure. If viral load can be counted then can that be used as an indication of the severity of the disease?

        If so, then when comparing different treatments we could match patients with similar viral load to see how effective the different treatments are for patients at similar levels of severity of the disease.

        Robert Clark

  18. WustlMed says:

    Does anyone have updates about the trial results from New York ?
    To CNN on April 22:
    Holtgrave, dean of the University at Albany School of Public Health, said he plans to finish his study analysis by the middle of next week, and publicly release it within a few days.
    “We’re continuing our work every day on this study and anticipate having our final analysis in place by the end of April,”

    1. Andy II says:

      Yep, I was wainting for the data as well. NY Governor, Cuomo, was questioned about the availability of the study results at their daily briefing a little while ago (a couple weeks ago?). He said that NY had sent the results to FDA. It is up to FDA when the data will be shared.

    2. DC says:

      Results were inconclusive. You can find the news reports if you google it.

      1. Robert Clark says:

        Did they break the results into two cases: 1.)patients early in the disease progression, and 2.)patients with severe disease? Dr. Raoult has said repeatedly HCQ has to be given early before severe lung damage has already set in.

        Robert Clark

  19. loupgarous says:

    Thanks for sharing those papers with us, Derek. The NYU and Cedars-Sinai papers show that HCQ’s not the mother’s milk that it’s been made out to be, You have to look at the more toxic cancer chemotherapy to see cardiac damage like that at therapeutic doses.

  20. Trew says:

    The original paper showing that chloroquine is an ionophore is lacking in multiple aspects that seriously call into question the papers conclusions.

    1. RNA says:

      Such as what…?

      1. Trew says:

        1. Chloroquine is positively charged under pysiological conditions. The Zn(II) cation, also being positively charged, would be repelled by charge-charge interactions.
        2. Many Zn(II) ionophores are bidente in nature, allowing for tighter binding to Zn(II). Chloroquine is most likely monodente within the cell.
        3. Figure 2a Increasing the concentration of Zn(II) 10-fold without the ionophore shows a significant increase in fluorescent intensity (2X). The percent increase holds steady as chloroquinone is added. In the absence of zinc, there was a significant increase in fluorescence for the addition of 300 micromolar chloroquine, suggesting either chloroquine helps concentrate the the fluorescent probe within the cell or that the medium was not properly scrubbed of Zn(II).
        4. Figure 3 Compare and contrast the 5 micromolar Zn(II) samples with and without 300 micromolar chloroquine in Figure 3a with that of Figure 2a. You will see a significant difference in the percent increase in fluorescene intensity. Unfortunately, FluoZin-3 results are very difficult to compare at the small cell count level. “When FluoZin-3 is used to estimate or compare intracellular labile Zn2+ levels under different conditions or in different samples, a large number of cells must be investigated to compensate for the signal variability at the single cell level.” In addition, ” FluoZin-3 co-localize with lysosomal markers in a variety of eukaryotic cells including HeLa cells”. PMC6177427

        5. Finally, “the combination of chloroquine with zinc enhanced chloroquine’s cytotoxicity and induced apoptosis in A2780 cells.” Apoptosis is known to effect Zn(II) ion concentrations in cells

        1. theasdgamer says:

          Mr. Trew,

          Your comment is very interesting. I can only speak to the first point. Hydroxychloroquine sulfate is an organic salt, so the HC must have a +2 charge as the salt. I believe there is evidence that HC acts as a base in endosomes. Hence, it seems that HC must be reduced somehow. I would expect this to occur at the cell membrane. Here is my very rusty biochemistry hypothesis. Likely one membrane-bound protein would catalyze the first two reductions of HC by a membrane-bound sugar. The sugar’s charge would be reset to neutral after each reduction by normal cell processes, costing ATP and producing CO2. Standard biochemical stuff. Once HC has a neutral charge, a different membrane bound protein catalyzes the final reduction so that HC- results, which is bound to the second membrane-bound protein. A third membrane-bound protein would then transport HC- into the endosome.

          Rinse and repeat for a second HC-, only the second time a zinc ion binds to the HC- before it is transported inside the endosome so that HCZn+ ligand results. The positive charge is shared over the whole ligand so that it is still able to pass the membrane’s lipid bilayer despite being weakly polar. The ligand bonds should be fairly weak, so that dissociation isn’t improbable in solution.

  21. Paul Blair says:

    With regard to no azithromycin: The study does say that antibiotics were part of the baseline treatment in 77.1% of the HCQ group and 89.4% of the other group.

  22. Warren Getler says:

    The much-overlooked question of zinc, in combination with hydroxychloroquine (as a zinc “ionophore”/transporter) is central to the entire issue surrounding hydroxy as a therapeutic for Covid-19.

    Anecdotal evidence from the field (numerous successful outcomes) is encouraging re the zinc-hydroxy combo when administered early. Med lit reviews re zinc as anti-viral (v. Coronavirus, ARDS) are promising (in vitro studies…see: 2010 UNC

    Notably, the Sars-Cov-2 virus uses RNA-dependent RNA polymerase for its survival, replication and proliferation. Zinc — a readily available, generally non-toxic mineral supplement — is a proven, very powerful inhibitor of this enzyme.

    Trials underway:

    Does Zinc Supplementation Enhance the Clinical Efficacy of Chloroquine/Hydroxychloroquine to Win Todays Battle Against COVID-19?
    Martin Scholz * and Roland Derwand
    Version 1 : Received: 6 April 2020 / Approved: 8 April 2020 / Online: 8 April 2020 (10:54:33 CEST)

    How to cite: Scholz, M.; Derwand, R. Does Zinc Supplementation Enhance the Clinical Efficacy of Chloroquine/Hydroxychloroquine to Win Todays Battle Against COVID-19?. Preprints 2020, 2020040124 (doi: 10.20944/preprints202004.0124.v1). Scholz, M.; Derwand, R. Does Zinc Supplementation Enhance the Clinical Efficacy of Chloroquine/Hydroxychloroquine to Win Todays Battle Against COVID-19?. Preprints 2020, 2020040124 (doi: 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.



    Abstract. In view of the emerging COVID‐19 pandemic
    caused by SARS‐CoV‐2 virus, the search for potential
    protective and therapeutic antiviral strategies is of particular
    and urgent interest. Zinc is known to modulate antiviral and
    antibacterial immunity and regulate inflammatory response.
    Despite the lack of clinical data, certain indications suggest
    that modulation of zinc status may be beneficial in COVID‐19.
    In vitro experiments demonstrate that Zn2+ possesses antiviral
    activity through inhibition of SARS‐CoV RNA polymerase.
    This effect may underlie therapeutic efficiency of chloroquine
    known to act as zinc ionophore. Indirect evidence also indicates
    that Zn2+ may decrease the activity of angiotensin‐converting
    enzyme 2 (ACE2), known to be the receptor for SARS‐CoV‐2.
    Improved antiviral immunity by zinc may also occur through
    up‐regulation of interferon α production and increasing its
    antiviral activity. Zinc possesses anti‐inflammatory activity
    by inhibiting NF‐κB signaling and modulation of regulatory

    T‐cell functions that may limit the cytokine storm in
    COVID‐19. Improved Zn status may also reduce the risk of
    bacterial co‐infection by improving mucociliary clearance
    and barrier function of the respiratory epithelium, as well as
    direct antibacterial effects against S. pneumoniae. Zinc status
    is also tightly associated with risk factors for severe COVID‐19
    including ageing, immune deficiency, obesity, diabetes, and
    atherosclerosis, since these are known risk groups for zinc
    deficiency. Therefore, Zn may possess protective effect
    as preventive and adjuvant therapy of COVID‐19 through
    reducing inflammation, improvement of mucociliary clearance,
    prevention of ventilator‐induced lung injury, modulation of
    antiviral and antibacterial immunity. However, further clinical
    and experimental studies are required.
    1. Introduction
    2. Zinc and COVID‐19
    3. Zn and respiratory viruses
    4. Pneumonia in adults and the elderly
    5. Pediatric respiratory infections
    6. Zinc and lung inflammation
    7. Zinc and S. pneumoniae infection
    8. Perspectives and conclusions
    1. Introduction
    Zinc is an essential metal being involved in a variety of
    biological processes due to its function as a cofactor, signaling
    molecule, and structural element. It is involved in the

    Zinc and respiratory tract infections:
    Perspectives for COVID‐19 (Review)



    I.M. Sechenov First Moscow State Medical University (Sechenov University), 119146 Moscow;
    Yaroslavl State University, 150003 Yaroslavl, Russia; 3

    Institute of Immunology, Medical Faculty,

    RWTH Aachen University, D-52062 Aachen, Germany; 4

    Federal Research Centre of Biological Systems

    and Agro‐technologies of the Russian Academy of Sciences, 460000 Orenburg, Russia; 5

    Department of

    Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY 10461, USA; 6

    Institute of Cellular

    and Intracellular Symbiosis, Russian Academy of Sciences, 460000 Orenburg; 7

    I.I. Mechnikov North‐Western State

    Medical University, 191015 St. Petersburg; 8

    K.A. Rauhfus Children’s City Multidisciplinary Clinical Center

    for High Medical Technologies, 191000 St. Petersburg, Russia; 9

    Center of Toxicology Science and Research,
    10Laboratory of Clinical Virology, Medical School, University of Crete, 71409 Heraklion, Greece;
    11Research Department, Innlandet Hospital Trust, 3159894 Brumunddal, Norway

    Received March 23, 2020; Accepted April 13, 2020
    DOI: 10.3892/ijmm.2020.4575

    Correspondence to: Dr Alexey A. Tinkov, I.M. Sechenov
    First Moscow State Medical University (Sechenov University),
    119146 Moscow, Russia
    Professor Aristidis Tsatsakis, Center of Toxicology Science
    and Research, Medical School, University of Crete, Voutes,
    71409 Heraklion, Greece
    Contributed equally
    Key words: zinc, coronavirus, SARS‐CoV‐2, pneumonia, immunity

    1. mjs says:

      The anecdotal evidence and the questionable clinical trials suggest that Zn is somewhere between useful and essential in the HCQ treatment. If Zn is active, doesn’t that imply that Zn level could be a significant uncontrolled variable in clinical trials? And that the proper approach would be (1) to measure zinc levels in the patients, or (2) give the patients enough supplemental Zn to drown out variation in Zn due to diet, electrolyte balance, etc., or (3) do an actual clinical trial with Zn as a variable?

  23. Lane Simonian says:

    Another anti-malarial drug, artemisinin may hold some promise in the treatment of the coronavirus

    Much attention is paid to IL-6 inhibitors but maybe more attention should be paid upstream to Nuclear Factor kappa-B inhibitors of which hydroxychlorquine and artemisinin appear to be two. (connection between Nuclear Factor-kappa B and coronaviruses).

    1. psoun says:

      Lane – old news here in sub-Saharan Africa. The president of Madagascar has been promoting this artemisia tea researchers there have developed, and there has been some interest in a number of countries on this. Whether it works of course is an open question – I’ve seen some research on its possible effects on malaria. But as always, show me some data.

      What interests me (and I’d love to get a number of takes from this) is not artemisia tea but properly synthesized artemeter (Coartem or AS/AQ) that is used for malaria treatment across SSA and Asia. There is an in silico study (link below) on the role that artemeter type drugs could play on Covid, taking of course all the caveats on in silico studies.

      But here’s the thing (a working hypothesis). Case and death counts for Covid are relatively low in Africa, especially in countries where public health systems and reporting are pretty ropey. Covid and malaria, symptomatically, in early stages present almost identically (fever/chills). Your average Joe in Kinshasa, or Lagos, or Yaounde, will have had malaria dozens of times and when the fever/shakes come, they’ll head down to the local pharmacy and pick up a pack of Coartem where a three-day course will do them right (they might still use CQ or Fansidar, but Coartem is typically standard here).

      So what I’d want to check is whether (a) there has been an increase in “malaria” in the past couple of months, especially in clusters where there have been Covid cases (there’s already evidence of this in Zimbabwe); (b) was Coartem or something else used; (c) do some serology to further investigate. If Coartem had cross-over effects for both malaria and Covid, we’d have something interesting to work with.

      In silico link here:

  24. OSWALD JAMES says:

    Are lay persons ALLOWED to input on this site? I wonder if someone can tell me WHY if Dr. Zelenko’s tri-drug combo was Claimed to have such Success that all the”Clinical Trials” I see DON’T include ZINC?? I think Jean-Paul Leonard was asking the same question but got NO response.

    1. loupgarous says:

      We lay people are allowed to comment (I’m not a physician, nor am I a medicinal chemist. I am a retired clinical data analyst). But if you read the entire comment stream, and Derek’s articles, those have the answers to your questions.

      None of us have an interest in concealing the use of zinc in Covid-19 along with ionophores. I personally take Co-Q 10 and other supplements with reported ionophore activity along with supplemental zinc, because I personally think the preponderance of the evidence favors a therapeutic role for zinc in Covid-19 prophylaxis.

      I don’t find Zelenko’s work notable enough to eclipse the larger clinical studies Derek’s commented on. Other people here may (and do) disagree with me on that and other points.

      1. Robert Clark says:

        There will be a clinical trial of Dr. Zelenko’s treatment soon:

        Hydroxychloroquine and Zinc With Either Azithromycin or Doxycycline for Treatment of COVID-19 in Outpatient Setting.

        Since this will be in an outpatient setting, presumably this will be for cases in the early stages of the disease, which Dr. Raoult and Dr. Zelenko have been arguing for repeatedly.

        Robert Clark

        1. JP Leonard says:

          This is the first CCT with zinc+HCQ for treatment I know of, there were some minor trials for prophylactic scheduled. Results only due Dec. 31. So even after Zelenko treated 1500 patients and got the attention of the White House it will still take 9 months for the findings to be published, after the disaster is all over.
          Covid19 has exposed a problem of enormous inertia in the healthcare system in responding to emergencies. The way forward to a more rapid response to the next challenge may be to facilitate physician to physician sharing of Quality Improvement findings.

    2. JP Leonard says:

      Yes We all have Derek to thank for keeping this an open thread even for those of us who have other viewpoints or backgrounds.
      I don’t know of many such open venues at a scientific level.

  25. Andy II says:

    Novartis clinical study of HCQ in COVID-19 patients is on-going:

    Experimental: Arm 1: HCQ + AZM placebo
    HCQ 600mg o.d. as loading dose (Day 1) +followed by 200mg t.i.d to be initiated within 8-12 hours of the loading dose (not to exceed 12 hours) AZM placebo o.d.
    Experimental: Arm 2: HCQ + AZM
    HCQ 600 mg o.d. as a loading dose (Day 1) followed by 200 mg t.i.d. to be initiated within 8-12 hours of the loading dose (not to exceed 12 hours) AZM: 500 mg as a loading dose (Day 1) followed by 250 mg o.d. Day 2 – Day 5
    Placebo Comparator: Arm 3; HCQ placebo + AZM placebo
    HCQ placebo o.d. (day 1) followed by HCQ placebo t.i.d AZM placebo o.d

    Primary endpoint: To demonstrate in patients receiving standard of care that the percentage who achieve clinical response with HCQ or HCQ/AZM is superior to placebo at Day 15

    They discuss MOA of HCQ in Brief Summary as: “…HCQ treatment may inhibit viral nucleic acid-mediated activation of various innate immune pathways, as well as blockade of lysosomal functions in cell types relevant for viral entry and antigen presentation.”

  26. TruthnScience says:

    The Wuhan study of 568 patients was registered as clinical trial TJ-C20200113:

    This was a trial of Chinese herbal medicines
    1.Shuanghuanglian oral solution
    2.Lianhua Qingwen Capsule / Granule

    This may explain why only 48 patients among the 568 patients received hydroxychloroquine; the no hydroxychloroquine group is actually these 2 herbal medicine groups. This may also explain the very high mortality rate in the “no hydroxychloroquine group”.

  27. Andy says:

    I have been taking HCQ myself for about 3 years, initially with 400mg per day and now with 200mg per day. The drug is considered to be very well tolerated and I have never had any relevant side effects. These are also the experiences made in the last 50 years, so even pregnant women can take the drug.

    Since the outbreak of Corona, I now hear about the worst side effects, which up to now have always played only a minor role, but suddenly should appear regularly. So either the drug is deliberately bad-mouthed because it is extremely cheap and not attractive for the pharmaceutical industry or then very high doses are given to very sick patients, whereby even a normal headache drug can suddenly be dangerous. Not to forget if you mix drugs together.

    By the way, HCQ does not cause potent immunosuppression.

    1. DrOcto says:

      Perhaps some side-effects that are normally not a problem, can be lethal if also fighting a specific viral infection?

  28. Jocco Dundee says:

    I am surprised that the following study was not mentioned in Derek’s article above. It was was “published” on the medRxiv site on April 26th:

    This study evaluated the effect of chloroquine treatment on time to clearance of SARS-CoV-2 via RT-PCR measurement. This was a prospective study, although not randomized nor blinded. However, given that the endpoint was more of a biomarker, these issues are less of a problem. Time to reach undetectable virus in the chloroquine group was 3 days (N~197; 95%CI: 3 – 5) vs. 9 days (N ~ 176; 95%CI: 6 – 9) in the non-chloroquine group. Given that the CI’s aren’t anywhere near overlapping, this result would be nearly impossible to achieve by chance (p < 0.0001) without intentional bias on behalf of the investigators. I have been very skeptical about the potential for chloroquine to impede viral entry into cellular endosomes, because the predictions from PBPK suggests that concentrations in the alveoli would be too low, given the in-vitro IC50. It is still possible that the anti-viral MoA is indeed mediated via the TLR7/IL6, consistent with the effect of hydroxychloroquine in auto-immune disease.
    The results of this study contrast interestingly to the remdesivir trial conducted in China, which interestingly did not show an improvement in viral clearance in the treatment group. I am not sure there is any proposed MoA for remdesivir to improve clinical outcomes without improving viral clearance.

    1. Derek Lowe says:

      That’s because I did the literature search for the latest papers on the night of the 3rd, and that one was published on the 4th. Thanks for flagging it! Next round. . .

      1. Jack Ryan says:

        And now there is yet another positive study: “Early Hydroxychloroquine Is Associated with an Increase of Survival in COVID-19 Patients”

      2. OC says:

        Yet you went back and added a postscript to your original article casting doubt on the positive Chinese study showing reduced mortality and lower IL-6 levels, yet made no mention of the two other studies that specifically undermine your argument for lack of anti-viral effect in COVID-19 with early HCQ treatment.

        This is also not the first time you have selectively added post scripts that cast doubt on HCQ while not correcting the record on issues with studies that report negative results for HCQ (e.g. the Brazilian study on high dose CQ administration that clearly had far sicker patients in the active arm).

        I’m sorry but you look less and less like an honest broker in this debate. I look forward to you discussing these two studies in your next piece. But I’m not holding my breath.

    2. rtah100 says:

      @ Jocco Dundee (Scots-Italian or more like Crocodile Dundee?)
      is the IC50 you are quoting a plasma concentration. The articles I have read in favour of HCQ make a point of noting its very high volume of distribution, so alveolar concentration may well reach the efficacy threshold even when plasma concentration is not so high….

      1. Jocco Dundee says:

        More like “Crocodile Dundee”.

        The PBPK model takes into account drug distribution into tissues throughout the body (i.e. the volume of distribution) and predicts drug concentration in those tissues, including alveoli, over many dosing intervals. I was also referring to chloroquine, which has a much lower volume of distribution vs. hydroxychloroquine. In theory, 400 mg hydroxychloroquine should be able to achieve alveolar concentrations that are far above its in-vitro IC50 (as opposed to chloroquine).

        1. rtah100 says:

          @ Jocco,

          Where did you get a lower volume of distribution for CQ cf HCQ from? My understanding is CQ has higher volume of distribution. e.g. 47,257 l for hydroxychloroquine and 65,000 l for chloroquine (from Nature paper,

          That crazy computational chemistry paper on non-structural viral proteins attacking haem may have been right for the wrong reasons. As an armchair detective, I’ve put the following jigsaw together:

          Sars-Cov-2 takes out all the ACE2 receptors

          Ace2 can no longer lower angiotensin 2 level properly

          angiotensin 2 upregulates haem oxidase and causes other reactive oxygen species to be created

          haem oxidase (i) degrades haem (ii) produces endogenous carbon monoxide and ROS oxidise Hbg to metHbg: result is blood that carries less oxygen and has free iron / haem problem, kidney damage and clotting issues etc

          HCQ suppresses haem oxidase and iron metabolism and helps reduce clotting

          (linked by Jack Ryan above)

          HCQ also improves NO synthesis (Italian ventilator protocol includes NO).

          IV vitamin C rescues any metHbg

          What it does not explain is HCQ as a post-exposure prophylactic. This paper from Korea needs more discussion. They dosed an entire hospital with it and prevented any infections. No control arm so we cannot say what would have happened in the alternative though….

  29. ezra abrams says:

    Dear Friends who are supporters of HCQ

    the question I have is, why are you so passionate and convinced that HCQ works ?

    we have, compared to standard drug trials, very little evidence that it works, and the evidence is mixed

    so why are you so firm in your beliefs ?
    what is it that allows you to believe so strongly that it works ?

    I honestly don’t get it

    PS: your heart beats every minute of your life. Any MD will tell you that cardiac symptoms are like the biggest red flag in the drug universe; iirc, cardiac side effects the #1 reason new drugs fail in clinical trials

    1. Anne Cookson says:

      This question has a flip side which is also not clear to me. Why are the ‘detractors’ so certain that cardiac issues are an issue here (e.g. safety, not efficacy)? Anecdote, I have taken HCQ as an antimalarial, no ECG was required, as have countless others. Was OTC many places as was chloroquine phosphate which has a worse side effect profile However, not anecdote, study with approximately 2 million patients:

      The issue of safety is an absurd hill to die on here when the side effect profile is well characterized.

      On the issue of efficacy, pretty simple to wait until the evidence is in rather than taking an advocacy approach as many appear to do for various reasons. The Chinese trials are coming in now, but HCQ+zithromax is essentially the standard of care many many places, and the ER and treating docs are essentially ignoring all of this chatter until the clinical picture clarifies while trying to do the best for their patients.

      1. loupgarous says:

        The side effect profile of HCQ in Covid-19 patients is an unresolved issue, and it’s there, with hospitalized and other very ill patients that cardiac toxicity is being reported. The Covid-19 disease process not only is more pronounced in patients with “metabolic syndrome” – poorly-controlled diabetes, hyperlipidemia, etc – but it’s in those patients, not in otherwise healthy patients not suffering from Covid-19 who take HCQ that cardiac damage is reported.

        1. Anne Cookson says:

          Indeed, but this has been reported particularly and anecdotally as an effect of the disease, not particularly an effect of HCQ. Simple to wait for the trials ongoing that will certainly answer that particular question, though perhaps taking longer than I was hoping. However, that objection for HCQ prophylaxis (trials ongoing including a large trial out of Duke) seems misplaced.

    2. blogreader01 says:

      Have not seen anyone here passionately convinced that HCQ “works” …

      Have seen a number of valuable assertions as to why HCQ most likely merits effective-weapon status at this juncture in the war against covid-19.

      1. DrOcto says:

        You just brought an image into my mind of a bunch of soldiers heading into battle holding untested weapons and very little idea of the enemy defences.

        All based on the report of that one scout that’s not quite sure what he saw behind enemy lines, amplified to truth by generals eager to end the war quickly, and cowardly scouts that saw nothing but are eager to claim they did.

        1. blogreader01 says:

          “Give me RCTs or give me death” is looking more and more like a bankrupt philosophy wrt HCQ and covid19.

          1. Some of the discussion in this thread reminds me of the discussion that led up to the CAST study 30+ years ago.
            The CAST study had to do with the treatment of certain arrhythmias that occur in patients having heart attacks. The occurrence of those arrhythmias in those patients is unequivocally associated with increased mortality. At least as far back as the 1970s, various medications were known to successfully suppress those arrhythmias, and cardiologists starting using them in these patients, at first with hope and later with confidence.
            Heart attacks were hardly a new problem, and everyone thought that the natural history of these events, with and without anti-arrhythmic medication, was pretty well understood. With accumulated experience in thousands of patients, many caregivers thought that the efficacy of anti-arrhythmic therapy was so well established that no randomized study was necessary or, indeed, even ethical.
            NIH did the study anyway, looking at encainide, flecainide, and moricizine. Mortality in the drug-treated groups was a bit lower than what had been expected by the clinicians who designed the trial. Good drugs, eh?
            Ah, but there was a placebo arm. Mortality in the placebo arm was two or three times lower than in the active-treatment arms. Shall I say that again? The patients who were randomized to placebo were the lucky ones.
            Now, maybe this story is noncontributory, because some of the anecdotes we’ve been hearing about COVID-19 treatments are REALLY GOOD ANECDOTES. And possibly there are metrics to show that our understanding of COVID-19 in May of 2020 is much better than our understanding of heart attacks 35 years ago, so a good mechanism-of-action argument (combined with those REALLY GOOD ANECDOTES) should be good enough, and any resources spent on RCTs would be wasted.

    3. Giannis says:

      Personally I only care about HCQ because in contrast to other antivirals it can be easily mass produced and potentially be used for prophylaxis. Just like people take Truvada we could be taking HCQ and massively reduce the chance of dying from COVID.

      But we need good studies first. Good old double blind trials.

      1. Jim Thompson MD says:

        We need RCTs, but not “first.”
        Thousands will die unnecessarily if we fail to make a good guess and it turns out HCQ is helpful.
        All we need to do right now is make a good guess, and if HCQ is safe, pass it out like candy.
        I am of the opinion that, with experience worldwide of hundreds of millions of doses, it’s safe.
        But do your own due diligence.
        And if you are a physician giving a patient the option, make sure they get the data.
        No one thought HCQ was unsafe until COVID started. LOL

    4. Tom Boyer says:

      I wouldn’t call myself a “supporter” of HCQ but if anything deserves a fair hearing in the court of science, it’s a drug that costs 6 cents a pill which is already prescribed safely on an outpatient basis to tens of millions of people around the world.

      If it works, it can be an outpatient drug given to a lot of people. That would save a lot more lives than a drug that can only be given as an infusion to hospitalized patients at whatever Gilead feels the market will bear (this being the company that charged $86,000 to treat Hep C). Whatever you think of remdesivir (and I’m hopeful) it is a medicine for the few, not the many, for the foreseeable future

      The other thing that’s promising about HCQ is a growing pile of evidence (especially compared with any other drug) that it actually helps. It’s no cure but it probably helps. Almost all of the studies are observational, all of them have flaws but they’re done in good faith by practitioners who have nothing to gain by pushing HCQ. (And BTW in the last two days, probably the two strongest studies released yet, one from China and one from Madrid)

      Not a day goes by without news stories around the world about how hospitalizations and deaths have rapidly gone down (Northern Italy, Rome, Sicily, New Brunswick, Madrid, North Africa, etc..) after HCQ was made part of the standard protocol — and ESPECIALLY in places where HCQ is given early in the course of the disease. And if you look at the daily death counts in those places, it’s … well.. intriguing.

      Yes there is some of the usual right-wing craziness pushing HCQ but people who think of themselves as respectful of science and interested in saving lives should be filtering that out.

      I’m decidedly on the left side of the political spectrum but I can’t think of anything more offensive than “rooting” against HCQ because one wants Trump to be proven wrong. There are 2,800 people dying each day.

      The current American standard of treatment, face it, sucks. Many people simply dying at home for lack of treatment/monitoring, which is a disgrace. A LOT of other countries with less resources appear to be doing better.

      Our treatment protocol is about as effective as our testing program, which is about as well organized as our social distancing rules. Maybe there are times when you could say, fine, let’s wait another year until we’re 100 percent confident about HCQ because we’re the US, we’re smarter, we’re better. But to say that right now looks very foolish and also could be resulting in tens of thousands of people dying unnecessarily.

      1. David Young MD says:

        Hydroxychloroquine is inextensive, but not 6 cents a pill. Back in early March, I checked out the cost of 60 tablets on various on line retailers. Most were 80 to 140 dollars for 60 tablets. A few suggested only 30 to 40 dollars per 60 tablets. So anywhere from 50 cents to a couple of dollars a pill.

        1. Mai Shensen says:

          “I checked out the cost of 60 tablets on various on line retailers… anywhere from 50 cents to a couple of dollars a pill.”

          I submit the online retailers are marking the pills up dramatically. Here in Taiwan the retail price per pill at the pharmacy in my neighborhood, who also has to mark the pills up enough to pay rent, is 4 TWD or 13 U.S. cents.

          I wish the drug had not been politicized in the U.S.

        2. psoun says:

          David – $6 for a box of 30 pills of branded Plaquenil in Dakar.

    5. Vincente Tenerelli says:

      Harvard Medicine, Kaiser Health: Growing number of reports now say coronaflu itself causes heart damage and arrhythmias, possibly due to lack of oxygen

      “inhibit the virus from reproducing or infecting other cells in a test tube. Within a week the highly regarded journal Cell Research published a PEER-REVIEWED letter by researchers at the Wuhan Institute of Virology that reported on two of these in more detail: chloroquine”

    6. Robert Clark says:

      The question can be asked of the other side why are so firm in your belief it doesn’t work when there has been abundant evidence that it does, especially when given early?

      Robert Clark

  30. pangolino says:

    I’d like to add to your “collection” of HCQ data this other news from an Italian newspaper.

    Please do note that where it says “manufacturers” in Italian we have “those who suffer from favism”.

    Best regards.

    1. Robert Clark says:

      Thanks for that link to the Italian report. It’s notable that the doctors quoted put the emphasis on giving the HCQ treatment early. From the translation:

      “I am a doctor and, positive for Covid19 , I immediately took hydroxychloroquine : in 3-4 days the fever and the other symptoms disappeared “. This is how Paola Varese , head of cancer medicine at the Ovada hospital in Piedmont , begins . “I applied the same protocol on myself that I planned for 276 patients at home,” continues Varese , stressing that “timely intervention by family doctors in patients’ homes is essential, with hydroxychloroquine associated with heparin (and if necessary the ‘ antibiotic ). It is presumable – he says – that the collapse of thehospitalization is due to the immediate use of the drug : we only had 7 hospitalizations: according to the projected expectations of the ISS we should have had 55 “.

      That’s a drop in the level of hospitalizations by a factor of 8. The need for prevention of hospitalization has now become abundantly clear, especially in New York. According to an article in The Hill, for a large New York health system only 12% of COVID-19 patients put on ventilators survived, so an 88% mortality rate for those on ventilators, and overall there was a 20% mortality rate for hospitalized COVID-19 patients:

      Large majority of coronavirus patients on ventilators in major NY health system died, researchers say.
      BY JOHN BOWDEN – 04/23/20 08:26 AM EDT

      Imagine if the Italian numbers of HCQ prevention of hospitalizations held true in New York. The number of hospitalizations and subsequent deaths could have been cut by a factor of 8.

      Robert Clark

    2. Robert Clark says:

      Can you confirm a couple of issues with the google translation of the Italian article? Here’s the google translation:

      First a percentage of hospitalizations appears to be 7% in the Italian version but google translate writes it as .7%. The 7% number seems more likely.

      Also there is a problem with the Italian word “sfebbrata”. The original Italian passage is this:

      [quote]Se prima del trattamento si avevano alterazioni della temperatura fino a 10-12 giorni, dopo l’introduzione sistematica di idrossiclorochina, il 75% delle persone si è sfebbrata entro il 4° giorno e l’85% entro l’8° giorno”.[/quote]

      Google translate gives this in English as:

      [quote]If before the treatment there were changes in temperature for up to 10-12 days, after the systematic introduction of hydroxychloroquine , 75% of the people choked by the 4th day and 85% by the 8th day “.[/quote]

      The English word “choked” doesn’t fit here since the doctor being quoted is describing positive benefits of HCQ. I did a web search and a better meaning here should be “fever broke”. This fits in the sentence since it is describing high temperatures.

      Robert Clark

  31. david c. says:

    Are there any reports that the in vitro results with HCQ or CQ were reproduced in another laboratory. Can anyone shed some light on that either with references or as a comment that their lab has been able to reproduce the data from D. Liu, Drug Clinical Trial Center, Peking University. It would be reassuring and supportive for the HCQ approach. I am not attempting to throw doubt on the report, just asking since this is what I would do if running a drug discovery program looking for improved therapy.

  32. Daniel P Hinz says:

    So I’m seeing the most successful ones as Dr Zelenko, Dr Raoult and his Senagalese friend. Tempered by the articles here.
    Dr Oz interview with Dr Raoult on youtube was very interesting for the care that the Marseille team has for patients using diligent patient supervision. Highlighting Gilead as a possible wannabe actor on the stage. Of course Tx City nursing home had a good outcome and searching for where Amneal has sent HDQ has been insightful.

  33. Logic Man says:

    OK, Tested positive for COVID, was sick for five days without the HCQ / AZ / Zn. OX saturation dropped to 85% after short walk. Took protocol, woke up in five hours being able to take a deep breath. (Slept on stomach, which also helped) OX saturation improved to 98%. I get it, this is anecdotal, but I truly felt something was rescuing me. After 5 days on the meds and Zinc, the fever broke and never returned. Was sick for a total of 10 days, and that’s at least four days shorter in duration than average. I have since fully recovered and tested negative on the PCR, and positive on the antibody test. I continue to supplement with the zinc, vitamin C and D and elderberry.

    So I cannot scientifically say that any of the above actually contributed to recovering, or if it was psychosomatic, or if it just eased anxiety. But, there is not a person who I care about in the world, that I would not urge to take this protocol, God for bid they acquire this virus.

    The day before I started the treatment, I couldn’t walk up my stairs without being out of breath and my oxygen levels dropping to 90%. Now, it really goes under 98%.

    I took at least 120 mg of Zinc, But also took other supplements that had various forms of Zinc, including zinc sulfate.

    1. Emmanuel Ohannessian says:

      Thank you for sharing

    2. DrOcto says:

      Who goes around measuring their O2 sats after they walk up stairs in their own house?

      1. Carvacrol says:

        I’m skeptical too, but *potentially* in their defense they could have one of those newer fitbits or apple watches that have O2 monitoring. Or comorbidity where they regularly monitor their stats and had a curiosity after what felt like extreme exertion? Of course, these HCQ ITP comment sections are loaded with trolls who only pop up when they spot their trigger word.

        Taking anything in a comment section/forum at face value is asking for a bad time, but especially when it’s completely transparent troll farms are out there sowing their seeds.

      2. JL in Jersey says:

        People with asthma often measure O2 levels. The finger meters cost about 25 dollars and work right out of the box.

      3. Robert Clark says:

        This emergency room physician recommends everyone get one of those over-the-counter blood oxygen sensors that you can put on your finger tip:

        The Infection That’s Silently Killing Coronavirus Patients
        This is what I learned during 10 days of treating Covid pneumonia at Bellevue Hospital.
        By Richard Levitan
        Dr. Levitan is an emergency doctor.
        * April 20, 2020

        The reason is it was found COVID-19 patients sometimes had extremely low blood oxygen levels before they even realized they were sick. So this doctor recommends getting these sensors as an early warning sign. They’re quite cheap only in the $30 to $40 range. Such sensors are also included in Fitbit-type health monitoring watches which can give your continuous readings such as when engaging in strenuous activity.

        Robert Clark

      4. Seebs says:

        When I thought I might have The Plague, I did indeed check O2 saturation under random circumstances throughout the day, because I happened to have the gizmo from some previous circumstance (I think we just got it as a pulse monitor originally, because I have heart rate issues sometimes) and it was handy.

    3. Nick says:

      I am in “healthcare” field . Co-worker went to ER and they gave medrol dose pk and sent her home. She was extremely tired, fever and starting to have difficulty breathing. HCQ was out of stock at local pharmacies but she found out of date bottle at home ( husbands old rx). She had 15 pills . She took zinc sulfate 220 mg , 1 twice a day , and HCQ 200mg , 1 twice a day. She had GI side effects of nausea and vomiting so she stopped after 3 days. She told me just with the 1 day of HCQ he was able to breath , otherwise it was very labored breathing . She was later confirmed by test to be positive for covid-19. Second story MD friend gave HCQ and zinc to cousin with Covid-19 positive and diabetes and heart issues , they were able to take the full course for 5 days and made full recovery. — just stories—-

  34. Coon says:

    Derecks a well known academic-startup propaganda mouthpiece. You can basically dismiss whatever he says as leftist political or serving some prof that needs something.

  35. Emmanuel Ohannessian says:

    Today’s numbers check the difference in no of deaths compared to recoveries between countries using it vs not:

    Confirmed Recovered Deaths
    US 1,235,652 +3,589 +2,325
    UK 194,990 N/A +693
    France 170,551 +1,365 +330 Some usage

    Spain 250,561 +3,085 +185
    Italy 213,013 +2,352 +236
    Russia 155,370 +1,770 +95
    Turkey 129,491 +5,119 +59

    1. OC says:

      There are none so blind as those who will not see.

      The sceptics will remain resolute in their opposition no matter how much observational data is collected that suggests early treatment is effective. Only until there is a rolled gold randomised clinical study will there be any acknowledgment.

      Even then they will probably insist on repeating it to see if they can get the same result.

      All in the name of science of course.

  36. psoun says:

    Derek – in the HCQ posts of yours I’ve seen so far, I’ve seen nothing on GNS561; care to comment?

    1. Wallace Grommet says:

      Genoscience has been touting and flogging that product for at least five years, for everything under the sun. A ton of marketing but where are the trials?

    1. Emmanuel Ohannessian says:

      Thank you for the excellent stats!

  37. Eric Paterson says:

    Report from AAPS here on observational studies here on HCQ with/without Azithromycin and Zinc

  38. Eric Paterson says:

    As of April 28th, “the total number of reported patients treated with HCQ, with or without zinc and the widely used antibiotic azithromycin, is 2,333, writes AAPS, in observational data from China, France, South Korea, Algeria, and the U.S. Of these, 2,137 or 91.6 percent improved clinically. There were 63 deaths, all but 11 in a single retrospective report from the Veterans Administration where the patients were severely ill.”

    From that AAPS report

    1. Derek Lowe says:

      Again, you’re not going to get very far with an AAPS citation here.

  39. Gene Reese says:

    Current COVID treatments for the seriously ill are largely ineffective because they are not treating the correct illness. Seriously ill COVID patients are suffering from severe cases of “hypersensitivity pneumonitis”.

    The proposed treatment does not treat the virus, itself, but rather hopes to prevent the more serious side effects that occur as a result of the viral infection. It can and should be used in conjunction with any anti-viral medications that may be deemed effective.


    Pneumonitis is a broad term that describes inflammation of the lungs and its associated symptoms.

    Hypersensitivity pneumonitis (HP) is a more defined type of pneumonitis. Traditionally, HP results as a response to an inhaled allergen or chemical; it causes fever, cough, shortness of breath, hypoxia at rest, ground-glass opacities on CT, pulmonary edema, and a number of other symptoms which seriously ill COVID patients also exhibit.

    The following whole-lung biopsy of a COVID patient provides even more insight to the similarities between HP and COVID presentation. Though acute HP biopsy presentation is difficult to come by (most patients with acute HP rarely undergo biopsy), sub-acute cases are fairly well documented and show a number of similarities:

    (Scroll down to histopathology for the HP biopsy information)

    I propose that the cause of HP in the case of COVID patient is not in response to an allergen, but rather by histamine released within the lung tissues by neutrophils responding to the viral infection.

    The discovery that human neutrophils release histamine in response to pathogens in the lungs is a recent one and is critical to the effective treatment of seriously ill COVID patients. The higher the viral load, the more severe the resulting symptoms of acute HP.

    It has also been demonstrated by numerous studies that all cases of HP have markedly increased levels of neutrophils present in biopsied tissues and that development of more serious complications from HP (such as fibrosis) were associated with higher levels of neutrophils:

    In animal studies with mice, the same neutrophilic production of histamine was verified – but they also discovered that intentionally afflicted pneumonitis symptoms were relieved proportionally to the amount of antihistamine that was administered:


    There are a number of studies that display a clear link between stimulation of the endothelial H1 receptor and increased levels of both thromboxane a2 and PGI2 (the latter of which should normally offset the increase of thromboxane as they work together to form a homeostasis in normal conditions).

    However, in the case of ischemia (a reduction of blood flow/oxygen to particular tissues – in this case, arising from injury to lung tissue), the production of PGI2 drops – swaying the blood to be more prone to clotting and the vessels to be more prone to constriction.

    When the drop in oxygen occurs, endothelial cells (stimulated by histamine release) produce thromboxane in greater amounts than they do PGI2. This results in the widespread clotting issues that occur in seriously ill COVID patients.


    Similar to the prevention and treatment of of radiation pneumonitis or chemical pneumonitis (well-known side effects of many cancer therapies), COVID patients should be treated prophylactically with antihistamines and COX inhibitors over the course of their illness. This should prevent the inflammation-derived pneumonitis from occurring to the same extent and should, additionally, prevent clotting issues.

    The use of diphenhydramine, cimetidine, and ibuprofen were shown (in animal studies) to effectively treat acute respiratory distress syndrome (which is a serious complication of pneumonitis and COVID patients) due to pathogen:

    However, this treatment could absolutely be improved upon as it is over 30 years old.

    Aspirin may be preferable to ibuprofen due to its irreversible COX inhibition, but diphenhydramine should be heavily considered as the H1 antagonist as its anticholinergic properties may also act against possible cholinergic inflammation of the lungs which can not be ruled out at this time.

    1. Nick says:

      Great info Gene and thank you for posting.
      Epithelial inflammation explained by Dr Seheult from YouTube channel Med Cram – episode 66 is another possibility.

  40. Jim Thompson MD says:

    It sounds like you think HCQ v not is sort of a “most papers supporting one side or another.” LOL.
    Interesting study out of Spain a couple days ago:

  41. FoodScientist says:

    I’ve taken 2xHCQ day for the last year. I was unaware of the QT issues, until recently.
    I was mainly concerned about the going blind thing after you take a total dose of 1,000g.

    I’m pretty sure that if any company had a cure they would have reason to pretty much give it away. There aren’t a lot of winners in the economic down turn.

    1. FoodScientist says:

      I’ve also had the novel corona virus 1.5 months ago. It was not fun. shortness of breath, dry cough, headache, GI issues, fatigue. No fever. But I was almost back to normal after 2 weeks.

  42. Jon Emeigh says:

    The Italian article is more interesting because it is the second one I have seen that hypothesizes that the virus is not attacking lung cells but red blood cells and that’s how blood oxygen levels are so low…because it’s preventing hemoglobin from binding with oxygen.

    That’s why some people propose that HCQ works,…because it’s basically following the mechanism whereby it defeats malaria.

    I’ve never heard of such a viral mechanism but is anyone else exploring that possibility?

    1. psoun says:

      Jon – that’s a really interesting hypothesis. Would that imply in any way that other (less toxic) anti-malarials such as Coartem or Malarone (at treatment dose) might have an effect?

    2. theasdgamer says:

      Hi, since SARS-2 targets ACE2 receptors, that would include epithelial tissues including “oral and nasal mucosa, nasopharynx, lung, stomach, small intestine, colon, skin, lymph nodes, thymus, bone marrow, spleen, liver, kidney, and brain”

      If SARS-2 targets heme as well as ACE2, then perhaps erythrocytes are deformed. Has anyone seen any slides of blood from covid patients?

  43. Chris says:

    Just heard from a reliable clinical source that doctors in Italy (I think they were associated with the University of Modena and Reggio Emilia Hospital) are routinely giving HCQ as early as possible with anti-inflammatories (anti-IL6) later. Timing is everything.

  44. Emmanuel Ohannessian says:

    The Effect of Chloroquine, Hydroxychloroquine and Azithromycin on the Corrected QT Interval in Patients with SARS-CoV-2 Infection;

  45. WustlMed says:

    Data from this publication,,
    suggest that hydroxychloroquine reduce patient death, although the authors claimed there was no difference using their primary outcome (death + intubation)

    1. Robert Clark says:

      Can you say where it showed HCQ reduced patient deaths? The conclusion of the authors was it had no significant effect.

      Robert Clark

      1. WustlMed says:

        Table S1, HCQ vs nonHCQ: Death, 157 vs 75; PrimaryOutcome (death+intubation), 262 vs 84. If based on the primary outcome with multivariate analysis HCQ and nonHCQ are similar (as the authors did and claimed), based on death, HCQ will show benefits

        1. Andy II says:

          Number of death was 157 in HCQ (n=811) arm (rate of death was 19.4%). Number of death was 75 in non-HCQ (n=565) arm (rate of death was 13.3%). Am I reading the data correctly?

          1. WustlMed says:

            Groups are different, HCQ group is more severe. Need multivariate analysis, as the authors did.

    2. theasdgamer says:

      Big surprise that the authors conflated intubation and death, given that the NIH funded the study. Politics in research needs to be called out. smh

  46. Napoleon Dynamite says:

    A retrospective study from NYU (900+ patients) suggests the addition of zinc to a regimen containing HCQ+Azithryomycin was associated with a reduction in mortality/transfer to hospice

    1. Robert Clark says:

      Thanks. That’s the first study actually showing some benefit to think for actual patients.

      Robert Clark

      1. Robert Clark says:

        Er, that should say “to zinc”.

        Robert Clark

    2. JP Leonard says:

      Thanks for the heads up, Mr. Dynamite!
      I was figuring we might get to “I Told You So” time eventually.
      Death rate 13% on zinc, 23% without zinc.
      Admittedly I was hoping the numbers would be even better, going on what Zelenko claims.
      Another report today, another “I told you so”, regarding “decontamination methods for personal protective equipment like N95 masks”
      “Within minutes, the majority of the virus is inactivated on surfaces and in the air in direct sunlight.”
      I distinctly remember being savaged here for suggested that light and air are healthy, when I cited an article in giving historical data from the 1918 Spanish flu.
      The CDC does mention UV lamps for decontaminating masks.
      But nobody there seems to know the sun has UV rays, and way brighter than lamps, too. Maybe they are all moles there.

    3. theasdgamer says:

      Mr. Dynamite, I just wanted to make it clear that you posted a preprint which hasn’t yet gone through peer review. The study is promising.

  47. Joe Psycho says:

    HCQ overdose seems to be responsible for the cardiac arrhythmias and HCQ related deaths

  48. Joe Psycho says:

    HCQ seems like a good adjunct to remdesivir.
    I thought remdesivir was the best candidate for treatment and/or prophylaxis in February and it is still what I would recommend more research on it especially in combination with low dose hydroxychloroquine (400mg/day total max) and/or favipravir

    Remdesivir seems like the most promising candidate and HCQ seems like a good choice for reducing inflammation and virus related damage and a potential weak antiviral and an overall good add-on treatment however it should be used in moderation to reduce risks (excessive doses seem to be used in some of the trials especially the ones with cardiac arrhythmias as a “side effect”)

    And I also think that bioavailability studies should be done with remdesivir to see if intramuscular or subcutaneous administration is possible for treatment or prophylaxis.
    If anyone has data related to remdesivir bioavailability studies it would be extremely helpful if you could share the results in a reply to this comment.

  49. Emmanuel Ohannessian says:

    Two studies for Hydroxychloroquine looking for volunteers:

  50. Jack Morris says:

    I have been reading about HCQ and Zinc treatments. You would think with all the principles of science, that this topic would be clear and concise. Like many who have made comments, I have sifted through many articles on the web, but it seems like a he said she said type of controversy. Through all of this I did find one website that might serve some use in the context of what treatments and medications Doctors are using to combat this disease. It takes a little bit of time to learn how to use the site, but the data is very interesting, particularly the worldwide usage of HCQ, Zinc and the new kid on the block Remdesivir.
    Give it a try:


  51. Navid says:

    We are a group of concerned physicians and scientists. We recently wrote a response to the Meyerowitz paper summarizing the HCQ evidence (different journal). For example that paper didn’t address the three top studies wrt HCQ.

    We’ve talked to the senior scholar at John Hopkins Center for Health Safety. The reality on the ground and in the minds of experts, is not lining up with the reality in the media and not even in the journals.

    In the interest of benefit, I am providing our slide deck (collating mostly published research).

    I do believe the backlash from this episode could be strong, and even worse if we don’t course correct.

    1. chiz says:

      Had a quick look through your slides. It was notable the way you cherry pick which HCQ studies to mention, and quote antibody surveys which supposedly show that lots of people have been infected with no harm even though those surveys are deeply problematic and quite possibly false. Then I got to the AAPS stuff, the Bill Gates conspiracies, the link between Newsweek and the CIA, and the Fauci conspiracies.

      1. theasdgamer says:

        Yeah, they should mention the VA study on HC, if only to point out that it invalidated Fauci’s dictat that HC only be given as a last resort. Seriously, mandating that an antiviral be given as a last resort?

  52. Emmanuel Ohannessian says:

    In 2005 Chloroquine was OK to use to fight SARS:

    1. RW says:

      “We report, however, that chloroquine has strong antiviral effects on SARS-CoV infection of primate cells.”

  53. Jack says:

    Sorry to report, but it seems that YouTube has just locked out many of Dr. Zelenko’s videos. Some of the ones that I viewed a few weeks ago will now show the message:

    “This video has been removed for violating YouTube’s Terms of Service.”

    These videos discuss his treatment plan involving HCQ, Zinc and Zithromycin, and his results. Not sure why this information would be censored, particularly now his treatment regimen (see Robert Clark’s post on May 6th) is undergoing clinical trials.

    1. loupgarous says:

      The US Food and Drug Administration (FDA) might have had something to say about Zelenko’s videos. I haven’t seen them, but if they promote a medication before safety and efficacy have been proven to FDA’s satisfaction, YouTube might have been advised that by publishing such videos, they’d be cooperating in an illegal activity.
      Or YouTube might have reached that conclusion on their own initiative.

      1. theasdgamer says:

        Too many nonpracticing academics are telling practicing physicians how to treat their patients. That needs to stop immediately.

    2. JP Leonard says:

      Time for bitchute

  54. Raúl says:

    A new treatment for COVID-19 has been proposed from Argentina. Dr. Beltramo`s group from Cordoba proposed to apply nebulizations using a soluble form of Ibuprofen in a hypertonic solution. It has been proven the bactericide and viricide action of Ibuprofen as well as the better known anti-inflammatory action, A small group of patients was treated showing promissory improvements. A proposed study testing the treatment of 40 patients is to be carried out under the supervision of the Health Ministry of the Province of Cordoba, Argentina. It was press released on Thursday 7th in almost all media in Argentina

  55. JJ Walker says:

    Retrospective study from France, HCQ+A associated with reduced in hospital morbidity

  56. Diego says:

    The author is a biased quack

  57. OC says:

    Retrospective study suggesting statistically significant reduction in HCQ + Azithromycin + Zinc Sulfate vs HCQ + Azithromycin alone.

  58. William Jackson says:

    I always liked “The Fixation of Belief” by Charles Peirce as a good starting point.

  59. Emmanuel Ohannessian says:

    Here’s how the drug should be administered: Everyone should listen to both sides of the story before making a judgement. Try it for a change!!

  60. JasonP says:

    OK here you go, a study that could ramp up the debate on the use of zinc with HCQ.

    For those who want an explanation of the results:

    Now we have evidence of the efficacy of Zinc with this disease, be it imperfect study design.

    1. Jack Morris says:



      The censors at YouTube are at it again:

      “This video has been removed for violating YouTube’s Community Guidelines.”

      Will they censor Trump’s recent announcement that he is taking HCQ + Zinc?

      Here is the President’s full presentation:

      If you want to see his endorsement and use, fast forward to 1:37:27


  61. Nick says:

    Study results on Zinc + Hydroxychloroquine + Azithromycin compared to Hydrozychloroquine + Azithromycin. It shows the combo with zinc had better outcome but it needs to be started early before the cytokine storm take over. Here is the study and MD explaining the results of the study.

  62. Jan van Westland says:

    The Treatment works when this cocktail is used:
    Zinc Orotate

    It has ony a function as an early treatment, where it helps to slow down the replication of the virus. So you have to give the cocktail as soon as possible after people are tested positive or get the symptoms. Once the virus has got a chance to fully develop in the body and cause a multitude of infections youare to late. That’s why they don’t find any proof of efficacy in studies whre they used the treament on patients with fully developed corona desease.
    The cocktail is very safe for people without hart or liver problems. Negetive side effects usually only occur when used for a longer period of time, however for use as corona treatment you only have to give it for a very short period of time. Used like that it’s very safe even safer than paracetamol….

  63. theasdgamer says:

    Something new…

    “Hydroxychloroquine and azithromycin plus zinc vs hydroxychloroquine and azithromycin alone: outcomes in hospitalized COVID-19 patients”

    1. Edwin Cannon says:

      Been taking 1% Ivermectin sterile solution orally for a month now as a preventative. I work 12 hour days with 400 people. 30 positives nothing for me. I never missed an hour of work. Say what you will folks but Ivermectin especially in low dosage works as a tremendous preventative. The angel of death has passed over our home that’s for sure.

  64. Raúl says:

    Maybe something really new to think about
    Here is the information so far reported about the trial using Inhaled Ibuprofen to Treat COVID-19

  65. Jack Morris says:

    Another study comparing HCQ + azithromycin vs HCQ + azithromycin + Zinc

    “The study looked at the records of 932 COVID-19 patients treated at local hospitals with hydroxychloroquine and azithromycin.

    “More than 400 of them were also given 100 milligrams of zinc daily.

    “Researchers said the patients given zinc were one and a half times more likely to recover, decreasing their need for intensive care.”

    1. David Young MD says:

      Retrospective study is not good enough. Do the prospective, randomized, controlled study.
      “Extraordinary claims deserve extraordinary proof”

      That study doesn’t prove anything.

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    1. David Young MD says:

      Something is not right about what Zelenko says. He has, in a Youtube video, stated on July 1st, that he has treated 2,200 Covid19 patients (with stellar results!). Now, if you are any physician at all, you would follow these patients along after their diagnosis. See them once when they have symptoms and order tests, see them a second time the next day to go over the tests and discuss your treatment plan, see them a third time in 3 to 4 days to make sure they are not getting worse (as well as making sure that their labs are not getting worse) and then see them back in 10 to 14 days to make sure that they have recovered well. For something as serious as Covid19, you need these return visits. If you’re going to brag about how remarkably well your patients have fared, then you need follow up. Maybe even a 5th visit. Here is the problem. 2,200 patients in less then 4 months. 16 weeks. You had 8,000 office visits in 16 weeks. 500 visits a week. 100 visits a day. You are telling me that Zelenko is capable of seeing 100 patients in a day’s work? 5 minutes to see each patient, examine them, go over their labs, make your office note, answer their questions, prescribe their medications, explain the plan, complete their disability papers, give them leave from jury, time off work, order labs and x-rays. Nope, not even close.

      So I have some real difficult believing that Zelenko is telling the truth.

  67. Jon Kern says:

    Hi Derek.

    For the HCL being given to RA and Lupus, doesn’t it make sense that there is no azithro+zinc? It’s not like they have a need for either (unlike a COVID patient).

    Yet you kind of sneered a bit, if I get your point about Dr. Raoult …

    Anyway, seemed like a less than objective comment. Shrug.

    The mysterious missing 65K article can not hide. I found it via the (aka, the Wayback Machine :-)) — now you can too. Simply enter the (broken) link you have into their form, and navigate to May 1st. You will find the 28 April article. Google Translate will reveal the basic text that was floating around regarding the 20 out of 65K — but no actual link to findings.

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