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Taking Hydroxychloroquine (May 19 Update)

I was not planning to revisit this topic just yet, but President Trump has forced the issue with his mention yesterday that he’s taking hydroxychloroquine. Let’s try to keep this short: does any regular reader here actually wonder what I might think about that? I know that the comments section here gets swarmed with people banging the HCQ drum – and the azithromycin drum, the zinc drum, and the rest of the percussion section – but I don’t think even most of those folks think that it’s much of a prophylactic. There’s a lot of talk from the fans of this treatment about how you have to give it early in the course of the disease, but how many of you folks think it’s a preventative? There’s no evidence of that, you know. Even if you think that there’s a ton of evidence for HCQ combinations as coronavirus treatments (and we disagree there), there’s no evidence whatsoever as a prophylactic. Come on.

So it’s been two weeks since that post, which is the last time I looked over the field. What’s happened since then? Well, there’s this preprint from a group in Madrid, an observational study over 164 coronavirus patients there. The team found that the mildest-affected cohort (at admission) seemed to show a benefit from early hydroxychloroquine treatment. But a comment to this paper has noted that the non-HCQ patients in the (retrospective) group actually showed higher levels of cardiopathy, dementia, and lymphopenia, so there’s a real question about comparability.

We also have this retrospective study from Northwell in New York, on 201 patients that were treated with various combinations of chloroquine, hydroxychloroquine, and azithromycin. The paper looks at QT prolongation, the cardiac side effect that’s been discussed so much. QT prolongation increased significantly in the drug combination group (as others have reported as well). Seven patients had to discontinue therapy due to cardiac effects, but there were no life-threatening Torsade de pointes incidents, fortunately.

There are others. But rather than do these retail, here’s a review of everything in the literature on COVID-19 and hydroxychloroquine treatment up to May 13. It summarizes eleven studies (3 controlled trials and 8 observational/retrospective efforts), totaling 2354 patients receiving HCQ (alone or in combination) and 1952 controls. Overall, there was no difference in viral clearance. No difference in symptomatic improvement. No difference in overall mortality. The only clear difference between the two groups was in adverse effects, which were (on again) higher in the HCQ treated population.

How about since May 13? Well, here’s an open-label randomized study from China in February and March (75 patients getting HCQ plus standard of care, 75 getting standard of care). They were looking for viral clearance by 28 days, and found no difference between the two groups, with more adverse effects in the HCQ treatment group (diarrhea and blurred vision, mostly). It does not appear that they took ECG data to look for signs of QT prolongation. And here’s an observational study from France, 181 patients who were on oxygen but not in the ICU. There were no significant differences in survival rate, transfer to ICU care, or continued use of supplemental oxygen between the patients who received HCQ and the ones who had standard of care treatment. But ten per cent of the patients in the HCQ group had to discontinue the drug due to cardiac side effects as shown by ECG monitoring. It’s safe to say that neither of these studies would modify the conclusions of the review of the literature up to the 13th.

Update: here’s a preprint from NYU on the combination of HCQ/azithromycin and HCQ/azithromycin/zinc. To the best of my knowledge, this is the first study to look at this under any sort of controlled conditions. It’s a retrospective of 411 patients with the addition of zinc sulfate (220mg, b.i.d.) and 521 on the dual combination without it. Let me quote from the paper directly:

In univariate analysis, the addition of zinc sulfate to hydroxychloroquine and azithromycin was not associated with a decrease in length of hospital stay, duration of mechanical ventilation, maximum oxygen flow rate, average oxygen flow rate, average fraction of inspired oxygen, or maximum fraction of inspired oxygen during hospitalization (Table 2). In bivariate logistic regression analysis, the addition of zinc sulfate was associated with decreased mortality or transition to hospice (OR 0.511, 95% CI 0.359-0.726), need for ICU (OR 0.545, 95% CI 0.362-0.821) and need for invasive ventilation (OR 0.562, 95% CI 0.354-0.891) (Table 3). However, after excluding all non-critically ill patients admitted to the intensive care unit, zinc sulfate no longer was found to be associated with a decrease in mortality (Table 3). Thus, this association was driven by patients who did not receive ICU care. . .

After looking for any other effects, the authors conclude that “After adjusting for the timing of zinc sulfate treatment, the associations between zinc and the need for ICU and invasive ventilation were no longer significant but we did still observe a trend.” They regard this as the first evidence that zinc might be beneficial in this treatment, but your own mileage may vary.

So once again, the evidence for benefit is weak and the evidence for adverse events is much stronger. Over and over we see similar results. Cue the folks in the comments, though, saying that none of that matters, ’cause these folks didn’t use zinc and they didn’t start early and they didn’t do the other stuff. Well, there are more clinical trials underway and more reports set to come out shortly, and if the data so far are any indication, you’ll all get the chance to try to explain their results away, too. As for you zinc folks, all I can say is see if you can get word to the White House, because I’ll bet that Trump isn’t doing it right, either. Update: apparently he’s said that he’s taking zinc, too and an “initial dose” of azithromycin. Oh joy.

As for the President himself announcing that he’s taking a drug that has not been proven to help patients with the disease, and that he’s taking it prophylactically (he is, right?) even though there’s even less evidence for that. . .and that the White House physician’s statement from last night doesn’t even resolve whether or not hydroxychloroquine has even been prescribed or whether or not Trump is actually even taking it for real (you never know), well. . .I could go on about all this, but what’s the point? My opinion of Donald Trump, his worldview, his judgment, his public statements, and his behavior are a matter of record. God knows this latest news doesn’t change my mind. And it won’t change the mind of any of the people who like all those things, either, of course. The time for arguing about Trump is long past. November’s coming. What will the US, and the world, look like by then? What will it look like after the election? That’s the argument. That’s when all these things will be settled.

227 comments on “Taking Hydroxychloroquine (May 19 Update)”

  1. JasonP says:

    Have you seen this preprint?

    Results: The addition of zinc sulfate did not impact the length of hospitalization, duration of ventilation, or ICU duration. In univariate analyses, zinc sulfate increased the frequency of patients being discharged home, and decreased the need for ventilation, admission to the ICU, and mortality or transfer to hospice for patients who were never admitted to the ICU. After adjusting for the time at which zinc sulfate was added to our protocol, an increased frequency of being discharged home (OR 1.53, 95% CI 1.12-2.09) reduction in mortality or transfer to hospice remained significant (OR 0.449, 95% CI 0.271-0.744).

    1. Derek Lowe says:

      That one’s in the meta-analysis paper I mentioned, FWIW. Not exactly the miracle effect of zinc that people are going on about, I have to say, is it?

      1. JasonP says:

        Not a miracle cure, but sans anything else available, isn’t a trend towards shorter hospitalization, decreased mortality and fewer transition to the ICU valuable?

        I am assuming under hospital care that the Doc are going to monitor for the known HCQ side effects and adjust accordingly. Not everyone is going to be a candidate.

        Not taking an adverse stance or stirring the Zinc pot, just hard to understand why this isn’t OK as long as it does no harm?

        I note:

        >>>The main finding of this study is that after adjusting for the timing of zinc therapy, we found that the addition of zinc sulfate to hydroxychloroquine and azithromycin was found to associate with a decrease in mortality or transition to hospice among patients who did not require ICU level of care, but this association was not significant in patients who were treated in the ICU. This result may be reflective of the proposed mechanism of action of zinc sulfate in COVID-19. Zinc has been shown to reduce SARS-CoV RNA dependent RNA polymerase activity in vitro [13]. As such, zinc may have a role in preventing the virus from progressing to severe disease, but once the aberrant production of systemic immune mediators is initiated, known as the cytokine storm, the addition of zinc may no longer be effective [17]. <<<<

        Yes, they give disclaimers and suggest further studies. But like the Marines, I suspect the docs fighting this disease are adjusting and adapting as they can. Maybe these resources are wasted on Zn & HCQ? Seems like a small sacrifice as we are tossing Hail Marys at this disease while waiting on the science to catch up.

        I'll get down off my soapbox and stand aside now. Thank you for allowing comments and your kind & thoughtful responses.

        1. D P says:

          The problem is that HQC and QC are necessary for treatment of other diseases and those people are are reported to be having a problem getting their usual supplies already, just on the recommendation of one doctor and very little scientific evidence of efficacy. Another problem is that, even under a doctor’s care, unknown side effects can occur that cause problems that might be irreversible.

          1. Carol MacDonald says:

            Hello DP you are correct and I’m beginning to think as we get further into this discussion of side effects that are unknown. I can tell you that my daughters grandpa jumped from his 6 th floor to his death after being released only one day after the 5 day treatment. I’m convinced it does have really bad mental health outcomes and may I suggests to the VA hospital. Keep your elderly patients longer to observe their mental state. My daughters grandpa was a very active 8& year old Korean War veteran. In his right mind before he was admitted. . This is very devastating and if I can make a difference I am going to have it mandated in Massachusetts. His whole hospital stay was 8 days. He did not need to be intubated. He is a healthy man. My phone number if you want some more info. 508 326 1416.

        2. passionlessDrone says:

          >> The main finding of this study is that after adjusting for the timing of zinc therapy, we found that the addition of zinc sulfate to hydroxychloroquine and azithromycin was found to associate with a decrease in mortality or transition to hospice among patients who did not require ICU level of care, but this association was not significant in patients who were treated in the ICU.

          I don’t know how treatment usually works, but do they have people who do get transferred to hospice or die, that do *not* goto the ICU first? I kind of thought the death route was:

          1. I’m fine.
          2. I’m sick.
          3. I’m at the hospital.
          4. I’m in ICU.
          5. I’m dead / going to hospice to die.

          Maybe the paper goes into detail to that point?

        3. Charles H. says:

          There *are* people who are deficient in zinc, and I would expect that for those people, adding zinc would benefit their immune system….over time. I’m not sure how much time.

          It’s also true, however, that excess zinc damages the immune system. I don’t know what the tolerances are, but they aren’t excessively tight, still… if zinc is generally protective, I would assume that means that the diet is deficient in zinc. This wouldn’t be surprising, but it also isn’t something that should just be assumed.

          IIUC, zinc is cumulative. So it’s best to be a bit cautious here.

      2. Eshan King says:

        You might be mistaken, Derek. I did not see the Carlucci et al paper mentioned in the meta analysis you referenced.

        However, IIRC, the retrospective study did not describe why some patients received zinc and others did not as the standard of care. I wouldn’t be surprised if there is some bias introduced here that could explain these results.

      3. angrygecko says:

        I don’t understand how a retrospective study on hospitalized patients can tell you anything about the efficacy, or lack there of, a prophylactic measure. Am I missing something?

        You could study prophylaxis on animals, but there’s no ethical way to run a meaningful test on humans.

        1. J N says:

          You just described a Phase III vaccine trial?

        2. rbell says:

          Trump is the rat being experimented on…at least so he says

          1. mario lento says:

            This article again plays on political clap trap. It is on the wrong side of history and tries to play it with ignorance. As I have stated before, HCQ is well know to work with Zn to stop RNA replication BEFORE the patient is overwhelmed. The studies done that show poor outcomes were flawed, fatally flawed. For doctors who use it correctly it in fact works extremely well, and prevents people from going to ICUs where by then it’s usually too late. Shame on the political torture which has led to death. History will eventually prove me and all of the doctors who saved lives on the right side. And your note about Trump shows your hate is misplaced.

      4. ghost of q.mensch says:


        Please let me enlighten you my dear Derek, and your readers. Being the non-corporeal form of the (4-Amino-)quinoline mensch, I can easily transposit back to the Oval Office on May 8, 2020 (2 weeks ago +/-) , to share with you and report the ethereal course of events unfolding shortly after both Trump’s personal valet, and the close staff of VP Pence were infected by the sneaky Corona-chan virus.

        So, being the germaphobe he is, the first thing out of Trump’s mouth was: “ Holy f**king s**t! Not the “six-ways-from-Sunday” Deep-State and that bug-eyed pencil-neck Schiff again?!
        Quick! I want all my CV tests repeated NOW! And not by anyone connected with the Pompeous one this time. Do them this time by someone Ivanka has cleared!”

        Trusted CV tester: “Mr. President, based on four independent repeat rt-PCR tests, we assess you to be POSITIVE for Covid-19, with a high degree of certainty.”

        “OK… For Chr*st sakes, I’m almost 74… Give me the full Raoult/Zelinsky/Chris Martenson HCQ recipe. What have I got to lose?… Do it now, while I’m still asymptomatic and at early viral infection stage—like the way you take Tamiflu—and not in 3 weeks like that stupid VA/NIAID study the Trump hating fake media constantly repeat, where everyone was started with HCQ only at a late-stage when everyone was on death’s door ventilator support.”

        It has been two weeks since then. No word about Pense yet. We will see what happens with Pres. Trump—and what the Trump-haters will say if he pulls through…

        1. Mr T says:

          It makes sense to take an antiviral in the early (asymptomatic) stages of infection. In the late stages, immuno-modulators are probably more appropriate.

        2. SAR says:

          ghost of q.mensch

          Truly amazing mind reading.

          1. rbell says:

            LMAO–truly deranged post…must be too much HCQ!!

      5. Ororo says:

        No one is forcing you to take hydroxychloroquine. You can take a ventilator when you get sick. But you stop imposing your will on other people, pretending you know what is right for everyone.

        1. Lappan says:

          Most folk like evidence-based medicine, since it has a better correlation with nice outcomes for us than faith-based. Being a pharma chemist, this blogger likes to discuss the evidence for pharma chemicals. And the evidence for hydroxy is decidedly weak, and getting weaker as studies pile up.

          Is there any evidence that could shake your faith?

      6. alvin hunter says:

        I’m just curious if you know about this however?

        Written: 5/17/2012
        The study found a 2.5-fold higher risk of death from cardiac arrhythmia in the first five days of taking azithromycin when compared with another common antibiotic or no antibiotics at all.

        Also to mention:
        Zithromax may interact with:
        anti-malaria medications (aka. Hydroxychloroquine)

        I’m thinking what this really means is most of today’s studies are reflecting on this very important fact. If zithromax amplifies the use of hydroxychloroquine, making it actually dangerous, then it’s not hydroxychloroquine to blame for all this. We all know Hydroxychloroquine has a safe indicator. Majority of studies were done by this.

        If you want a true roundup of studies, look here:

        This has just about every study to date.

        Now, if you take a closer look, any study that has about over 600 mg of hydroxychloroquine or even the “new” study of chloroquine of (ugh…600 mg) of it, you will find it “no benefit”. Most of these studies were actually built to fail, thus the big pharma is trying to tell the american people, or any people for that matter, that their vaccines are more important. In my opinion, they are equally important, but shouldn’t be shooting down a cheap alternative to what actually may be a good thing.

        200 mg has been shown to work in majority of patients who took it, and took it early. Matter of fact, if you change out the antibiotic being used, you might actually find success such as this doctor who found success using nothing but…

        He used doxycycline, a different antibiotic. Therefore, found superb results. now only if we combine that with zinc (a known viral inhibitor) and we might have found a winning combination.

        1. mario lento says:

          Yes, HCQ is a Zn sensitive ionophore, which gets the Zn into the acidic alveolar cells of the lungs. Otherwise the Zn will not make it through because of the +2 charge of the Zn ion. When in the cells is does in fact stop nearly 100% of the RNA replication of the virus. It also has an effect of alkalizing the alveolar cells which make it difficult for the spike of the covid 19 to attach to the ACE2 receptor. So it has two effects. The Azithromycin causes the elongation issues, and should be used with caution. The HCQ and Zn together given early work extremely well and prevent nearly 100% of the need to ever get to the ICU.

          My sources are medical sites, and Medccram This information should be researched before writing so many articles that are plagued with political bias.

          I strongly recommend that the author here get information and post what you will soon enough find out is the truth and please credit me for steering you in the right direction.

          I will come back and make the point that articles like this do not inform people on the whole correct side of the story.

          I welcome your strong feedback.

          PS – the Lancet caused countries to stop the testing because of studies which needed to be retracted because good doctors found out they were duped with intentionally bad data.

          Get the story right and try to understand the mechanism of HCQ and Zn which has been know for well over a decade and we can only guess why it is not being used widely… It’s cheap.

          PS – to those parroting the false narrative that it’ takes away from Lupus and arthritis patients. This stuff is dirt cheap and easily manufactured in any quantities needed.

          The safety is over 99.999% over its 70 year history.

    2. Arnold Grossmann says:

      new NYU study is the final proof that HCQ helps significantly with Zinc at early stage. Which is why it is not significant for ICU patients. This is obviously due to the fact that HCQ alone might not help at all, but with Zinc yes, because it lets Zinc enter the cells, and it is proven that Zinc keeps the virus out of the cell. So, thje cell wont get infected. At late stage, cells are infected and even with Zinc, it is game over.
      But it is an incredible and final victory for Trump that HCQ plus Zinc helps! If everyone takes it early stage, most ¨late stages¨ can be avoided. As HCQ is the only widely available and cheap product, the truth is that Trump prophetically found the solution!

      1. Colin Hunter says:

        Yup. I read the preprint study too and that’s exactly the successful mechanism at work. In pre-ICU patients the percentage of ICU/ventilator admissions decreased by 50%. One can speculate that the earlier the treatment is given the higher that percentage is too. The writer of this blog referenced the study, not sure why he’s not accurately portraying the results.

    3. jeff marc says:

      HCQ was used to STOP AFIB in trial with heart patients.
      Google Afib hcq
      It may become a treatment for AFIB
      Where is the clinical data on patients taking HCQ for other ailments like Lupus
      malaria and others regarding their heart effects.
      THis drug has been prescribed for years, if there was negative clinical regarding
      effects on heart arrhythmia it should be well documented by physicians already!

  2. Dr. Victor Frankenstein says:

    It is just a matter of time until local drug dealer will offer hydroxychloroquine to their customers …

  3. Moose says:

    What I wonder is *why* Trump is really taking Hydroxychloroquine.

    Is it just stubborn insistence that he was right?

    The president has access to the largest information gathering machine in human history… maybe he knows something we don’t?

    Is it a calculated political move, just to stir up trouble and stay on the front page? To weaponize Hydroxychloroquine as a political tool? It certainly worked, if so.

    Spooked by the infection of his staff, does he actually believe it works as a prevenative based on anecdotal evidence? Are his aides pushing that, or was that opinion formed from external sources like TV? Is it all just bluster?

    About the only thing I’m sure of is that he’s *not* tallying studies… and that creating one of the most politicized drugs in history can’t purely be an accident.

    1. dearieme says:

      He’s taking this drug because he’s under the mind control of the evil Mr Putin who wants him dead of heart problems so that the Dems can replace marblesless Joe by Hillary who will then become a biddable Prez because Putin knows her price.

      Because it’s obvs.

      1. Hap says:

        I’m pretty sure Putin (and nearly everyone else on the planet) knows Trump’s price, so having a more biddable President would be an equilibrium in Trump’s favor (also considering his love for (white) dictators, he would likely be more favorable on that score).

      2. karen-km says:

        Likely he bulllied the physician into prescribing it; likely, if taking anything, they gave him a placebo to pacify him. I haven’t seen any studies that Hydroxy would have any prophylactic effect at all; I read in a Rheumatology journal that people with lupus and arthritis currently taking the drug are still contracting covid19. I couldn’t find any further anecdotal information on it though.

        1. alvin hunter says:

          This has all the studies you will ever need.

          In it, you should find a ton of studies.
          But I recently found something, that is intriguing and should be an eye opener to a lot of people.

          in which states:
          The study found a 2.5-fold higher risk of death from cardiac arrhythmia in the first five days of taking azithromycin when compared with another common antibiotic or no antibiotics at all.Also to mention:

          Zithromax may interact with:
          anti-malaria medications (aka: hydroxychloroquine) in which amplifies it.
          Here is what CBSNews had to say:

          Even though it is only observational, the size and scope of the study gives it a lot of impact, said Dr. David Aronoff, infectious diseases chief at Vanderbilt University Medical Center.
          Notice both “studies” came from the same outlet (vanderbilt) , one written in 2012 and one more “recent”. Makes you wonder what the connection is…..

    2. b says:

      He does own some stock

      1. NotADoc says:

        1. It’s a generic.
        2. He owns index and mutual funds, and is not allowed to actively managed allocations even in those diffused instruments.

        There are many things one can object to regarding Pres Trump, and also about the long time political players. Accusing him of attempting to profit off a generic is, in my view, a cynical play to people who’ve never directly bought a stock or fund, which is a large group.

        I don’t believe it was appropriate for him to talk up HCQ nor to announce he’s using it; fools are determined to find an outlet and people have actually eaten Tide Pods because a prankster called it a “challenge”. Then again, fools gonna fool, and you’d be one to stand in their way.

    3. chiz says:

      why? Its a combination of faecocephaly, the Dunning-Kruger effect and wanting to distract people from the Pompeo story.

    4. Daniel Jones says:

      If Don Trump is taking it at all (as opposed to just being fed TicTacs by savvy staffers) it’s because he’s a noted germaphobe.

    5. Barry says:

      We don’t know that Trump is taking hydroxychloroquine. We know only that Trump says he is taking hydroxychloroquine. He says all sorts of things that simply aren’t so. He might be lying. His physician may be giving him something that he tells him is hydroxychloroquine.
      It all looks like an effort to fluff the value of an ethical pharmaceutical* as if it were a vacation property or a luxury handbag.

      *in which he or his family may have a financial stake

    6. Ken says:

      What you may be missing is that he thinks that he is “the largest information gathering machine in human history”, and knows more than all the doctors and scientists put together.

    7. x says:

      We have to remember that this is the person who suggested administering disinfectant to sick patients and shining bright lights on them.

      Putting aside the question of whether he IS actually taking HQ – and Trump is a VERY unreliable narrator – I wouldn’t put much credence in the notion that he knows something secret about this bug that none of the studies have so far elucidated and that’s why he’s on a regimen that still hasn’t been proved to do anything beneficial. I would absolutely believe that his physician, or somebody, suggested this to him, or he read about it somewhere, and that’s why he’s on it. I would also believe he’s politicizing it somehow, because Trump has one known skillset, and that’s being a conniving huckster.

      1. Charlotte says:

        THIS is what trump was talking about
        He is not the best articulator

        UV light therapy-developed at Cedars Sinai


        Internally Applied Ultraviolet Light as A Novel Approach for Effective and Safe Anti-Microbial Treatment

    8. Ryan says:

      Trump may be an idiot, but the politicization of the drug is entirely the media’s fault. I think HCQ would have been a minor sub-theme (while still discussed in forums such as this) were it not for the fact that those in media made it their hill to die once the Orange One mentioned it. There are far more important things to discuss in presidential briefings than his personal health regime.

    9. Charles Shaw says:

      This study from 2014 details the interaction of Zinc and Chloroquine. The use of this treatment didn’t drop out of thin air. Doctors all over the world are using it effectively. 44% fewer deaths may not mean anything to you but it will to the American people when they find out that the MSM has caused as many deaths because after all, Ornagemanbad.

      1. Ray says:

        Yup, can’t be talking about that now, can we? This Derek Lowe has an interesting history when it comes to writing articles about important topics. He attacked Judy Mikovits here in sciencemag, along with the “nice” lady over at ERV (who was calling Judy a c**t evidently), which he linked to about the XMRV story being “proven” false and seemed happy that her phenomenal work proving the retrovirus connection was being destroyed by fraudulent studies, commissioned by none other than Tony Fauci. And I bet he’s lamenting how people are picking up her “nonsense” all over again…sorry buddy, it’s not “over with and done”.

    10. mario lento says:

      Derek Lowe: I am addressing you as I respond to this post who mentioned politics re: Trump.

      My following note and links will fortify you to have a better perspective for which to write a future article.

      Trump did not politicize HCQ… the Left has done so by lying about it. It is very difficult to find the truth now a days. Look at some information such as from this link, took me 10 minutes. If you watch these you will then be qualified to at least understand this subject.

      Nothing here posted is subject to opinion, it’s basic medical information telling you what the science is, without any political spin.

  4. Mike R says:

    I am a hospitalist physician in NYC who totally agrees on the agnostic approach to HCQ until higher quality evidence is out. But I am surprised you didn’t mention the recent preprint from NYU about HCQ and zinc significantly decreasing mortality by 44%. Yes, yes it is still a retrospective study, but it is probably the highest quality retrospective we have right now on HCQ (the two cohorts looked T were essentially the same, unlike most if not all other HCQ studies that show HCQ group sicker at baseline than control).

    1. Mitch Trachtenberg says:

      That is one excellent question, Mike R, and I’d urge Derek Lowe to explain to his readers and editors how he could have left it out.

      1. Derek Lowe says:

        Malice. Of course. Evil intentions, and a desire to see people die. I mean, what else could it be? But if I go in and update the post, we’ll have to search for another explanation.

        1. Mitch Trachtenberg says:

          I’d suggest that rather than wasting time on sarcastic replies, you simply do your job.

          1. Derek Lowe says:

            Blogging, as it turns out though, is not my actual job. . .

          2. Some idiot says:

            @Mitch: Mate, get real… Derek owes no one anything, and particularly not to a more or less first-time sniping visitor. The quality of his blog over the last decade speaks for itself. Anyone who knows Derek and the blog knows that if there is something important he missed (and hasn’t been covered by a previous blog, or a review he mentioned), well, it will come up later.

          3. Mitch Trachtenberg says:

            I stand corrected. This is not your job. Rather than wasting time on sarcastic replies, just feel free to ignore me and that hospitalist who was wondering about the excluded report. Never mind, and good bye.

          4. Wallace Grommet says:

            Where you born a bastard, or are you a self-made one?

          5. Barry says:

            I’ll remind you that this is Derek’s ‘blog. If you like it, read it. If you have something to contribute, contribute! If you’ve come to snipe and snark, you can start your own ‘blog for that. Maybe your mother will read it out of charity.

          6. Miles says:

            Go bore people somewhere else.

          7. Andrew Molitor says:

            Everyone thinks he’s the lone voice of reason, sailing in here with the critical piece of evidence that reveals that Dr. Lowe was wrong all along.

            The trouble is that there’s one of you blokes every five minutes, and all the other ones have had trash instead of evidence. Eventually a fellow gets sick of running down yet another false lead (in one’s free time) and starts just barking at these people.

            This is sort of a bummer if it happens that you actually are *not* a kook with another piece of trash evidence. In fact, it’s a bummer for all those kooks, because each and every one of them is equally convinced that, while all those other guys are kooks, they are NOT.

            On the internet there is no good way out of this trap. Dr. Lowe is taking the standard approach, which is the only pragmatic one, which is to start waving anyone away who fits a profile which has — thus far — reliably proven to be “kook.” If you have a suggestion other than “But you should take ME seriously, because I PROMISE I am not a kook” (all kooks offer that one) then by all means share it.

        2. Kurt says:

          I am also disappointed in the quality of your reporting. You are leaving out a big part of the picture when you leave out the hydroxychloroquine and zinc interaction and leave out the well done retrospective study that suggested HCQ/zinc saved 44% almost twice the number of lives than compared to HCQ alone. There are high quality scientific papers, statistical analysis, and case studies that suggest zinc is the important component in preventing the virus from replicating and HCQ is just playing a helper role. To leave this out and not giving readers the full picture is just adding to the confusion on this treatment.

          1. kismet says:

            The problem is it really doesn’t matter whether a retrospective study is well-done or not. These are purely hypothesis generating and almost worthless to base clinical decisions on. No, we don’t need to “throw hail marys” at the disease as another poster suggested. We need to carry out large, well-designed randomized controlled trials. Meanwhile, the effective treatments for SARS-CoV2 are known and widely employed throughout the world, the only effective treatment is a strong public health response like in South Korea.

    2. Eshan King says:

      If I recall correctly, the authors did not describe why some patients received zinc and others did not, as the standard of case. I have a sneaking suspicion that there is some biased introduced here that might explain a lot of this effect.

      1. Mike R says:

        Of course this is certainly possible. But as it stands now, looking at the characteristics between the two groups in this study, they look remarkably similar in terms of clinical characteristics. Needless to say, this study isn’t proof of anything aside from the fact that this is simply still a truly open question that needs to be answered with randomized controlled trials. Meanwhile, the media seems to be just as brazenly sure as trump about HCQ clinics efficacy, except on the opposite side.

        1. Mitch Trachtenberg says:

          This is exactly what I see as well and it’s a bit crazy-making, so thank you.

          No, the evidence is not in and, no, nothing yet is the gold standard. But it is beyond me how anyone reporting on the best available data can lump a bunch of things into “retail” and not report on the NYU result, while sharing whatever caveats they think appropriate.

          1. jim says:

            official publication by Dr. Fauci’s in Virology Journal on August 22 , 2005 search this and see what he said about it. He gives high praises on both of those products.

    3. Yohanan Weininger says:

      heh Mike R, Your post is empty without reference, link to “the recent preprint from NYU about HCQ and zinc significantly decreasing mortality by 44%…. highest quality retrospective…” An actual medical scientist hospital physician would know about citation. So I guess you’re not the NYU hospitalist you claim…

  5. Dionysius Rex says:

    Can the WHO please expel the USA until sanity has returned?

    1. Thomas says:

      Perhaps the States can become individual members?

    2. Hap says:

      That could be a while. Maybe WHO can have a satellite office to make sure things don’t leak out into the rest of the world?

  6. luysii says:

    Similarly, the country is undergoing a social manipulation (the various lockdowns) that has not been proven to prevent the spread of the disease (I know, I know — it seems logical that lockdowns should work, and China says that they did if you believe their statistics). Various parts of the country are lifting lockdowns to varying degrees at different rates in what are basically uncontrolled trials and the results will be instructive.

    The first results are from Georgia which partially lifted some 25 April. There has been no explosion in cases or deaths, but it’s early times. For details see the excellent Georgia Department Public Health website —

    For why it’s still early times even though 24 days have passed since the 25th please see

    1. Kismet says:

      Lockdowns are exceedingly effective. The more severe the social distancing the more effective it is. I have never seen any good contrary evidence and it wouldn’t make much biologic sense, however, there is evidently a way to control the disease more efficiently and there must be some level of diminishing returns. Japan and South Korea are doing a good job with relatively mild social distancing, for example, whereas in Sweden and Singapore the level of social distancing appears (or appeared) to be so mild as to be almost useless. I think there is a less political way to say “we can do more with less” rather than saying “lockdowns don’t work” as you seem to be doing.

      This is just one example from a couple days ago:
      “..we were able to relate the inferred change points to the three major governmental interventions in Germany: We found a clear reduction of the spreading rate related to each governmental intervention and the concurring adaptation of individual behavior (Fig. 3), (i) the cancellation of large events with more than 1000 participants (around March 9), (ii) the closing of schools, childcare centers and the majority of stores (in effect March 16), and (iii) the contact ban and closing of all non-essential stores (in effect March 23).”

      1. Larry says:

        Link bad. Does distancing explain the similarities between say, CA and TX?

        1. Hap says:

          Population density, use of public transit, and density of people in public spaces are likely significant differences (though depends on location – SF likely but LA/SD?) between the two.

      2. Trebitch says:

        “Lockdowns are exceedingly effective.”
        Absolutely. So far 36 million lost jobs, half of those will never work again. Misery, broken families due to economic stress, suicides, non-treatment of patients because of hospital reorientation to COVID, delayed cancer diagnosis and treatment, etc. It surely did not need double-blind randomized studies, as it is obviously great! Sick bastards! Enjoy the mayhem your beloved “Dr and Scientist advisors” generated.

        1. Lebowski says:

          This mayhem was generated by Donald Trump. Take it up with him.

          1. Trebitch says:

            Dixit insipiens in corde suo: Non est Deus. Corrupti sunt, et abominabiles facti sunt in studiis suis; non est qui faciat bonum, non est usque ad unum.

            Ducunt Fata Voluntem, Nolentem Trahunt!

        2. Hap says:

          If you didn’t want the economic mayhem of lockdown, you could have kept measures to limit infection spread (hint: not looking for infection where you don’t want to find it is not a good strategy), or you could have been more aggressive at testing and tracing (yes, it actually matters when you don’t bother to have competent people in charge at federal agencies), or you could have had a better safety net in case stuff happens (businesses being asset-light to make more money doesn’t work when things break, not that investors care). This is the economy and society Trump and the GOP have wanted for a while, and its failures under coronavirus are consequences of its design. If you don’t like what it looks like, then perhaps you should think about what you actually want society to do. Of course, if that involves being immune to physical and biological realities, well, then you’re probably going to be disappointed in any case (or dead, since viruses do not care about your rights or your economic desires).

          1. Trebitch says:

            “If you didn’t want the economic mayhem of lockdown, you could have kept measures to limit infection spread”,
            I sure could have. Mea maxima culpa. Dimitte nobis debita nostra, sicut et nos dimittimus debitoribus nostris.

      3. Charles Shaw says:

        Lock down nursing homes like Fort Knox. Stay at home orders for those over 65. Let the rest achieve herd immunity. Fastest way back to normal.

    2. karen-km says:

      @Luyssi: RE: Georgia…. I understand they manipulated their data…. either intentionally or unintentionally by arranging the dates of the data out of sequence. Others, no doubt, are being pressured to “conform” to the hypothesis…. I’m not in the medical field, but honestly, I’ll try linoleic acid before someone takes a shotgun approach of “try this, it may work, and it might also kill you”.

      1. luysii says:

        Please look at the first graph in the website ( titled COVID-19 cases over time. It has been quite similar for days. The manipulation of the data you mention (mixing up dates) refers to something else. You can look at the data in the graph 3 ways — 7 day moving average of new cases/day, total cases and 7 day moving average of daily deaths.

        They don’t regard their data as solid until 14 days have past, due to reporting lags, which is why I say it is too early to say that removing the lockdown didn’t have the disastrous effects predicted by many (10 days after decreasing the lockdown is still in the range of the lag time between infection and symptoms). In fact, the 7 day moving averages of both new cases and daily deaths appear to have peaked 3 days before the lockdown, and have been declining since.

        1. Some idiot says:

          I agree that you need to wait 2-3 weeks to see the effect of any intervention (or removal thereof). But there is no doubt from other countries that lockdowns have been extremely effective.

          1. intercostal says:

            I agree there are good prior reasons to think lockdowns should work.

            But there isn’t that clear of a pattern… probably because the hardest hit areas had more motivation to take stricter measures. Some US states have taken more limited measures (South Dakota, Arkansas, etc.) and have not been hit hard. Sweden is not doing *great*, but it’s doing a lot better than early models would have projected (hospitals are not overwhelmed, etc.)

            The difference in outcomes between urban and rural areas (and, to a lesser degree, between northern and southern cities in the US) seems much more dramatic than was expected (at least what got out to the general public) back in March.

            Florida and New York have almost exactly the same population, and closed down on about the same timeline. Yet New York has 14 times more deaths…

            I’m not saying that lockdowns didn’t help – they probably did. But I do think it’s not clearly obvious from comparing different states and countries that they did – because of other effects that seem to make an even greater difference.

          2. Hap says:

            Population density probably helps – if you don’t come into close contact with as many people, you are likely to be less efficient at spreading disease and less likely get it, and if your daily interactions mean you’re with lots of people, then there’s a good chance of community spread and a good reason to lockdown. For places with lower population density and less random contact, where people live further apart and don’t come into contact with as many people, less stringent measures might work.

            If you don’t know what relaxations of lockdown will work, though, then it’s hard to relax at all because if the disease spikes then the (reduced) costs of the lockdown are sunk (and it makes it harder to lockdown again if another pandemic shows up because it didn’t work and you can’t be sure why). It seems like it would be difficult to test as well what relaxations work other than in a pandemic when you don’t want to test.

          3. confused says:

            >>If you don’t know what relaxations of lockdown will work, though, then it’s hard to relax at all

            We kind of need to, though. Modern economies are big and complicated things, and the possible downside of major disruptions is much worse than anything this virus can do.

            Even the worst-case of this pandemic is not any threat to society/civilization going forward. But I don’t think anyone can say that supply chains etc. would be OK if we tried to lock down for, say, a year.

            Even if infections did spike again (and I think we’d be seeing a rise in hospitalizations if that was going to happen), I doubt it would be worth it to lock down again.

          4. Hap says:

            My point was that you want to do one lockdown that you know will work (because you can’t do it again, or for an extended period of time). So testing what aspects of lockdown are necessary and unnecessary is wrought with anxiety, because you have one chance to get the lockdown right for the pandemic, and if you mess up you’re wasting lots of lives and money. (If you go too far, you are likely wasting lots of money and pain – recessions strangely have been cited as decreasing death rates in a Fortune 2019 article, but you can fix the financial consequences in other ways, while unless you’ve become God or a zombie master, death can’t be fixed.) Because of that risk, governments are likely to do a hard lock when they have to do one at all. Different aspects may be relaxable in different places, but because the situation when you call a lockdown is so urgent, we may not be able to find out which ones (even if we have a longer attention span than usual, it may be hard to get definitive data, though maybe retrospective data will help?)

          5. confused says:

            Yeah, that makes sense.

            One point, though:
            >>you can fix the financial consequences in other ways, while unless you’ve become God or a zombie master, death can’t be fixed.

            It’s not just the consequences to things like the GDP, which yeah, can be affected by policy. Modern economies are a web of really complex inter-connections, and I really don’t think there was enough analysis of the effects of the lockdowns on that before we decided to do them.

            It looks like it is going to work out, since much of the US is reopening, as are some European countries – but I think the risk wasn’t taken seriously enough when the decisions were made.

            (And while I do think the lockdowns did some good – saved some lives – I don’t think the effect was as large as expected beforehand, since several states did more limited measures and seem to be OK. I really doubt most of the US would have seen overwhelmed hospitals even without any official action.)

        2. anon the II says:

          For me, it’s instructive to look at Louisiana. Fat Tuesday was the 25th of February and the Ugly didn’t show up until early May, almost 5 weeks. I wouldn’t expect to see anything so dramatic in Georgia since many there are probably not going to restaurants, etc. I just expect to see the death rate fall off a lot slower. Just slow enough to kill a bunch of people and still let everybody say “See, I told you”.

        3. luysii says:

          I don’t think manipulation is an accurate term for what happened. The following appeared on their website 17 May

          “Alert – May 17, there was an electronic processing error which inadvertently included 231 serologic tests results in the number of positive COVID19 cases. This error was corrected, but caused a decrease in positive cases between reporting periods on our dashboard. We are working diligently to provide the most accurate information, and we apologize for any confusion.”

          Please look at the data in their first graph

    3. Loonybean says:

      I am lucky enough to live on an island with @110,000 population (Jersey), and both us, and our neighbours Guernsey, have eliminated community spread (as far as we can tell) with a strict lockdown, which was in place for 6 ish weeks, and is now in the process of being slowly and carefully lifted. The lockdown has certainly worked, I just hope we don’t act too quickly on lifting it, and inviting a resurgence. Lockdowns DO work, us, New Zealand, South Korea et al are proof of that, the numbers don’t lie.

      1. cancer_man says:

        So one commenter says South Korea didn’t really lockdown much and you think their lockdown proves lockdowns work. South Korea already had 3,000 known cases when they urged people to stay home, although their constitution states that can’t be enforced legally.

        Japan’s request for people to stay home happened in mid April after they had way more cases than South Korea yet their per capita deaths are about the same.

        1. Hap says:

          I thought SK was a counterexample to lockdowns – you could minimize limits to businesses and public interactions if you had lots of testing and tracing, and the power to quarantine contacts if needed. If effective, it would mean that lock/no lock (or businesses or life) is a false dichotomy – you could do targeted measures, ruthlessly, and achieve the same effects as lockdown. The method requires lots of things that we didn’t or weren’t willing to do for it to work, though, and a competent national response as well, so we ended up with what we have instead.

    4. Donal says:

      Lockdowns work quite well as other posters have pointed out. Here in Ireland we were starting to implement restrictions from mid February, with progressive tightening to a near complete lockdown from March 27th: travel limited to journeys to buy food/essential items, care for relatives, or for essential workers to travel to their place of work; other travel limited to a 2 km radius of home, with police support by way of checkpoints on roads from time to time. Those in high risk groups had to shelter in place.

      If you look at the figures at for daily new case count, you can see that they start falling from mid April, about 2 weeks after the lockdown went into effect.

      The massive spike on April 10th was due to delayed test results finally being processed, and Worldometer didn’t backdate the data (it’s just taking aggregated figures from the government’s daily report. The data at reflects delayed test results backdated to when the test swab was taken. There are some other one day spikes but overall the trend since mid-April has been downward and we are now taking the first tentative steps towards opening up again.

      And in case you’re going to write us off as some sort of socialist dystopia, our current government is one of the most right wing we’ve had in a long time. I guess it helps that our prime minister is a medical doctor though (and has gone back practicing part time to help out during the pandemic) and our government generally is taking its lead from scientific experts.

      1. ghyu says:

        Of course full lockdown works, but what’s the added benefit of lockdown over social distancing without complete lockdown? In Europe there certainly doesn’t seem to be a correlation between how harsh the lockdown was and how quickly new infections and deaths per day went down (e.g. Netherlands vs Belgium). I think we’ve been forgetting to properly take superspreading into account. For example the overdispersion parameter was 0.57 in France ( and was estimated to be 0.1 by others (, implying that 80% of infections are caused by 10% of infectious people. If superspreading drives the pandemic, it may be sufficient to prevent superspreading events by limiting the maximum size of gatherings without having to ban all other contacts.

        1. Charles H. says:

          IIUC, one consideration not mentioned here is air circulation patterns. I’d expect lower rates of infection where the air circulation patterns were vertical rather than horizontal. I.e., say, air flow from the ceiling down to outlets on the floor. If, as reported, the primary carrier is very small droplets, that would tend to limit their time to pass between people. Horizontal flows, however, would tend to facilitate the spread.

          This is clearly a bit difficult to address by changing things around, but perhaps it sometimes can be thus addressed. (Fan position, etc.) And it should certainly be mentioned more carefully in case studies. The one in the Chinese restaurant clearly pointed to this as being significant in facilitating spread between persons nominally not in close contact.

      2. Forte Shadesof says:

        The death peak 14 days after lock down Means lock down did not work. Infection to death is 20 days plus. Previous Jess severe interventions did the job.

  7. Rob says:

    Wouldn’t it be nice to have a randomized controlled trial of HCQ + azith + zinc with enough patients to see a difference if there is one? Then we could all move on to other matters.

  8. Adrian says:

    I wonder whether the President of the United States of America simply made it up, or whether they were giving him a placebo just like his staff has been improving his diet.
    “But we were working on his diet. We were making the ice cream less accessible, we were putting cauliflower into the mashed potatoes.”

  9. Fred Sanford says:

    A real RCT trial of HCQ for post-exposure prophylaxis and early treatment finished ~2 weeks ago, but the results are have not been published yet (and will not be put out as a preprint)

    1. John says:

      Just a hunch, but possibly, the DSMB stopped the trial(s) when they met on April 22nd, due to an early positive result. The authors are being very circumspect to not release their findings before peer review, suggesting that they are submitting to a journal that strictly enforces this, such as the NEJM.

  10. RTW says:

    Ok what about Vitamin D levels? Seems some believe that people with low levels of Vitamin D have a worse response to Corvid-19. Can’t cite where I saw this unfortunately. I have for a number of years been taking it 5000 units every other day, especially in the winter I find it likely a good idea since I don’t get outside much nor drink significant amounts of milk anymore. I’ve taken as much as 10K per day. Now I have to say – Colds and flu have been infrequent and minor for the most part. But that’s a count of 1. Not statistically significant. Still its easy to do and has known benefits.

    1. Halbax says:

      It is almost a cliche, but correlation does not equal causation. People with low vitamin D levels are likely to have a number of other risk factors (poor diet, etc) that could worsen the response to covid.

      1. rtw says:

        Yes – I understand that correlation is not causation all too well. I have said that for years! I am a Medicinal Chemist by training. Now doing ChemBio Informatics. and knowledge management. I find the correlation interesting nothing more. I am just fed up with the politics of HCQ, and the fact that no amount of teasing the numbers are going to produce strong evidence that HCQ is more helpful than harmful. Elongated QT is the kiss of death in drug discovery. Your lead compound increase QT its back to the drawing board for most therapeutic indications. Hell – its such that they won’t even accept it in new anticancer drugs anymore, and these things tend to be pretty toxic!

    2. Dr. Victor Frankenstein says:

      Here is a preprint about vitamin D levels:

      “The Possible Role of Vitamin D in Suppressing Cytokine Storm and Associated Mortality in COVID-19 Patients”

  11. Tomas says:

    If you were the White House physician (who is generally a military officer and needs to obey direct commands), would it be more ethical to lie and give him the zinc and placebo, or be honest and give him the actual thing?

    1. Hap says:

      They serve the country, not the President. In any case, the hydroxychloroquine would be the problem; heart side effects in Trump would be no good, while the zinc and azithromycin are likely to have less threatening side effects. I guess I’d give him a placebo for HCQ and Azithromycin and hope he doesn’t read the pills he takes (or Google searches for pill shapes). It seems hard me to tell what will drive him crazy about this, so trying to keep him calm and sane seems difficult, other than yessirring my way towards end of watch. (I’m not a doctor, though.)

      I don’t understand his fixation with HCQ (other than hoping all this will go away, but that ship has sailed, I think), but I haven’t understood anything on that side of the aisle for quite some time.

      1. NMH says:

        The fixation is a conspiracy: that the government is in cahoots with the pharmaceutical industry, and this evil duo does not want the populace a cheap and simple way out of this pandemic, by getting HCQ which is generic.

        This is right and wrong. Its wrong to think they are in cahoots in this case, but the cahoots is correct in a different context: medicare, section D. The govt will pay whatever the pharmaceutical industry wants here.

  12. M says:

    The whole politicization of this is disgusting (but oddly amusing too). Trump taking HCQ (is he really taking it? He lies about a lot of things), and Pelosi saying he shouldn’t take it because he’s morbidly obese is analogous to Patrick picking on SpongeBob.

    1. Hap says:

      Does Pelosi understand how HCQ works and its side effect profile? That would not necessarily seem to be in her domain of expertise. Maybe she should just let President Trump make a fool of himself and stay out of his medication decisions (the aphorism about arguing with a pig comes to mind).

      1. M says:

        She does know tuna fisheries and ice cream. The whole thing is quite the spectacle.

        1. Hap says:

          Yes, but it would be much more amusing if it were someone else’s country (preferably one without lots of nukes or bioweapons lying around). I feel like I’m living in Raskolnikov’s fever dream, and I’m not sure who’s sane (I mean, I can’t not be sane right? [/sarcasm])

      2. Tom A says:

        In her defense she did day “listen to the scientists”. So that’s an appropriate appeal to authority. Yes what she thinks and believes matters – she’s third in line.

        1. Hap says:

          That’s better, but it would still be good if she’d leave the being a nutweasel role to the President and his people. They’ve had years of practice at it and you can’t just expect to get that kind of skill at the drop of a hat or a virus. Not that people aren’t trying, though.

      3. Charles H. says:

        She may not know HQC, but she does know politics. That was a political comment, and a rather effective one.

  13. psoun says:

    What about this out of Korea?

    Between starting at eclipses and taking HCQ, if Trump is taking it, he’s not going to be able to see anything at this rate!

    1. Robert says:

      From the linked article: “However, it is not sure if PEP was effective because there was no control group.”

      PEP in this case is Post-Exposure Prophylaxis with HCQ.

    2. PB says:

      Out of Korea:
      “HQ with antibiotics was associated with better clinical outcomes in terms of time to viral clearance, and resolution of cough symptoms compared to Lop/R with antibiotics or conservative treatment.”

      1. D P says:

        This hasn’t been peer-reviewed yet, so it could have problems. For example, it is a retrospective study which has these flaws ( or Secondly, at a cursory review level, the methods section seems incomplete and when it comes down to it the sample sizes are small (n=35, 20, 40). Finally, if there was any statistical proof that HQ made a difference they would use a stronger term than “associated with” when describing the results.

  14. idiotraptor says:

    Given Trump’s exhaustively documented penchant for lying, it is not unreasonable to speculate that he is taking neither HCQ or zinc and that his pronouncements are purely a political play. Perhaps he has no awareness or care that his son, Eric, near simultaneously asserted that the the coronavirus pandemic is a Democratic hoax that will disappear after the 20220 election. What a pathologically ignorant family.

    1. M says:

      I hope we’re still having elections in 18, 200 years.

    2. Hap says:

      Ignorance has paid off so far for them, though. Why stop now?

  15. Dr. Ector says:

    I am no doctor but what harm can it do? I hear it might do some thing… but maybe nothing. We would be better off if Trump quadrupled his dose to 800 mg/day of hydroxychloroquine. It would certainly make sure he doesn’t catch the virus.

    1. Detergent Injections Inc says:

      And then HQ would end up saving millions of lives after all

    2. Paul D. says:

      It can cause Long QT Syndrome, which can kill you.

  16. David Young MD says:

    Here are eleven studies of Hydroxychloroquine as a preventative treatment for exposed patients. These were derived from There are a few more, I believe. Most are recruiting. A few opened 6 weeks ago and are still not recruiting. The number of expected enrolled subjects varies quite a bit. Some of these have projected completion dates of a year or two from now, which means to me that they are being to ambitious. But that date may be an arbitrary set. Clearly, some of these studies will enroll faster than others. Only one of these studies adds zinc to the mix and it is one of the studies that probably won’t recruit very well, at least no in my opinion. Clearly scientists are interested in testing Hydroxychloroquine as a preventative. One would think that it would not be difficult to recruit, if they include household contacts. For every covid19 patient, you would think that you could find two contacts and there must be many exposed health care workers.

    1) Baylor, health care workers, randomized placebo, no zinc, 228 patients, active, not recruiting:

    2) Sanford Health (South Dakota), health care workers and community exposure, randomized placebo, no zinc, recruiting

    3) Barcelona, Health care workers, randomized, placebo controlled, 440 participants expected, no zinc, recruiting

    4) A Cambridge study limited to patients on dialysis

    5) Columbia University, randomized, placebo controlled, 1600 patients expected, no zinc, recruiting

    5) Cambridge University, health care workers randomized two dosing strategies and placebo, 1000 participants expected, no zinc, recruiting:

    6) Several Detroit hospitals: Health care workers, randomized two dosing strategies and placebo, 3000 participants, no zinc, recruiting

    7) Eight hospitals in France, mostly in Paris. Health care workers. Randomized to either Hydroxychloroquine alone, Azithromycin alone or placebo. 900 participants expected. No zinc

    8) Seventeen Locations in the US: high risk health care workers, randomized placebo controlled, 15,000 participants expected, no zinc recruiting

    9) Six hospitals in the United States: household contact or health care worker: randomized to hydroxychloroquine or vitamin C, 2000 participants expected, no zinc, recruiting

    10) New York Center for Travel and Tropical Medicine, Randomized placebo controlled, Not Yet Recruiting, no zinc

    11) ProgenaViome in Ventural, California, Medical Workers exposed, placebo controlled, randomized. Uses Zinc, vitamin D and vitamin C in addition to Hydroxychloroquine. 600 participants expected.

    1. David Young MD says:

      One more:

      12) Five hospitals, Minnesota and Canada, household contact or health care workers, 3,000 participants, randomized, placebo controlled, no zinc, recruiting

  17. Giannis says:

    We now have many animal models for SARS-CoV-2. If HCQ worked we would have seen a preprint by now.

    1. Grump says:

      Yes, one study with negative results:

  18. Fix News and Friends says:

    The Donald has been heavily medicated with placebo – i.e. fake pills for a fake. He’s just bullsh%ting as usual. It’s all he knows – it’s all he is.

  19. Daren Austin says:

    We analysed the Gautret data properly and concluded a clear signal for the combination, but nothing really for mono therapy. Extrapolation of this data forward to improved outcome and backwards to prophylactic use is nonsense.

  20. Sunyilo says:

    The irony of things is that there are a lot of folks out there – you know in big trucks, US flags mounted and toting automatic rifles – who would take HCQ in heartbeat; yet they protest the use of face coverage that even assuming that a reduction of viral flux – in or out – by 50%, it could lead to a 4x reduction of r0 population-wide.

  21. Sulphonamide says:

    Are we still expecting data from a (more or less) definitive trial for HCQ? Those of us (sooner or later) expecting to have to explain all this to our students (could probably teach almost the entirety of many a biomedical degree just based on events and publications from the last 3 months) would certainly appreciate something from which a result of some sort can be declared with a reasonable degree of confidence.

    1. Marko says:

      “NIH begins clinical trial of hydroxychloroquine and azithromycin to treat COVID-19
      Study enrolling adults with mild to moderate COVID-19 in the United States”

      “…The Phase 2b trial will enroll approximately 2,000 adults at participating ACTG sites(link is external) across the United States. Study participants must have confirmed infection with SARS-CoV-2, the virus that causes COVID-19, and be experiencing fever, cough and/or shortness of breath. The investigators anticipate that many of those enrolled will be 60 years of age or older or have a comorbidity associated with developing serious complications from COVID-19, such as cardiovascular disease or diabetes. Participants will be randomly assigned to receive short-term treatment with either hydroxychloroquine and azithromycin or matching placebos…..”

      No zinc , natch. No results expected before the end of the year , natch.

      Why now ? To make us think this is the definitive trial , and we should just cool our jets and wait. There will likely be 2-300k dead from COVID-19 by the end of the year , but what’s the rush?

      The results will suggest that those in the trial who supplemented with zinc on their own had better outcomes , which will prompt a new trial to investigate that possibility. Results end of 2021. Be patient , sheeples. All is well in the world of big-pharma.

  22. Peter B says:

    Data, or something resembling it, may be coming from India.

    According to a letter to the BMJ,

    “The municipal corporation of Greater Mumbai (BMC) has decided to roll out a seven-week-long course of chloroquine (CQ) and hydroxychloroquine (HCQ) mass community prophylaxis for the people living in slums. The decision is apparently backed by the announcement of the Indian Council of Medical Research (ICMR) dated 22nd of March, for the prophylaxis of asymptomatic healthcare workers involved in the care of suspected or confirmed cases of covid-19 and asymptomatic household contacts of confirmed cases.”

    The ICMR advisory is here:

  23. RA says:

    Such a contentious issue! A few thoughts:

    1. If the President is actually taking Hydroxychloroquine, I would guess that he had an ECG to look at his QTc interval both before and after the initiation of therapy. And my guess would be that he would only stay on it so long as the QTc is good…but he has the ability to be monitored in a way that most of the public would not, especially since our outpatient systems of health care are largely dormant these days because of the pandemic. Maybe Trump can take the med safely since he can be monitored…can you? Can the people who are poor, uninsured, without a primary care doc who also happen to be bearing much of the burden of this pandemic?

    2. It seems there is a lot of conflation of pre-exposure prophylaxis and post-exposure prophylaxis in a lot of the media/online discussions. 1st, if you believe the timelines out there re the white house outbreak, what Trump was trying to do was POST-exposure prophylaxis. Let’s for the sake argument say that the cocktail “done right” of Hydroxy/Azithro/Zinc is effective for POST-exposure prophylaxis (with ECG monitoring or just winging it?)…even in that rosy scenario, it doesn’t mean that the risk-benefit would be acceptable for PRE-exposure prophylaxis for a) those at high risk or b) the general population. In either scenario, but especially for b, the number of cardiac issues/adverse effects could outweigh the number of those whose infections are prevented. Need the data first!

    3. I think this pandemic is a time when we need to emphasize absolute changes in risk, not just relative ones. For example, the NYU observational study which is generating excitement…ok, say for the sake of argument the 44% (relative) reduction would hold in an experimental study, look at the last page of the pre-print…the percent who died in the zinc group was 13.1% vs 22.8% in the no zinc group. The absolute risk reduction (9.7%) isn’t anywhere near 44%, the relative reduction…but it is easy even for those who are medically trained to fixate on the 44% number.

  24. luysii says:

    If you’re the sort who likes statements to be true or false (e.g. the law of the excluded middle) then

    Condition A implies Condition B (statement 1)
    is true

    (statement 2) not-condition B implies not-Condition A (called the contrapositive)

    must also be true

    We have many commenters here saying that
    condition A (lockdowns) imply condition B (decreased incidence of COVID19 and death) (statement 1 with flesh on its logical bones))

    The Georgia experiment is the contrapositive ‘

    not condition B (increased incidence of COVID19) implies not condition A (lifted lockdowns) (statement 2 with flesh on its logical bones).

    If the contrapositive (statement 2) is not true (e.g. the incidence of COVID19 and death does NOT increase) then neither is statement 1. We’ll see what happens.

    But if statement 2 IS true — this proves statement 1, something so far lacking as all we have is correlation, not causation for statement 1.

  25. MPK says:

    Introducing the True and only Trump Tonic ™: the mixer of choice for your G&T in the COVID era. Contains hydroxychloroquine.

  26. Dan Meehan says:

    Any thoughts on this pre-print?

    Seems to suggest some potential upsides to HCQ + antibiotic

    1. David Young MD says:

      One of the biggest mistakes over the past 3 months is the lack of randomized, placebo controlled studies. I am tired of one retrospective study after another. Although this preprint looks “interesting” it is still retrospective. “But the differences are remarkable” you say. There is one major problem…. How do you know, pray tell, that there are not another 20 experiences where a physician or group of physicians do not bother to publish because in their observation there is no improvement with Hydroxychloroquine. In this South Korean publication, some one or some group of physicians thought that they were observing improvement in those people who received Hydroxychloroquine. So, what did they do? They went on to do a more detailed analysis and, eureka, the detailed analysis confirmed their suspicions that people who got Hydroxychloroquine go better. They publish. Now think of another 20 groups of physicians. They don’t notice any improvement, they don’t do a detailed analysis and they don’t publish. So, the “positive” results are from chance alone. (you do 20 studies and it is likely that one will be “positive” even if the drug doesn’t really work.) I am just underscoring the need for a large, randomized, placebo controlled study. There are such studies, but they took about 7 weeks to get started. They should have started one back in late February.

      1. anon the II says:

        I have a better idea. Let’s forget this HCQ stuff and focus our time, talent and money on something else. If it was really any good, I think it would be obvious to all, not just the Trumpsters, by now.

  27. george douglas says:

    Since Donald Trump commented on hydroxychloroquine (HCQ) as a Covid-19 therapy, the drug has become a political football. The link below provides a compilation of 120 clinical studies of HCQ for COVID-19, some completed and some still in progress:

    If one defines a drug as “proven” when a broad consensus forms regarding benefit, HCQ is “unproven”. At the same time the claim of “no evidence of efficacy” is disproven by the above compilation of completed studies. In particular read these links:

  28. Lane Simonian says:

    Make America Sane Again!

  29. loupgarous says:

    Answering your question, Derek, I’m a firm believer in randomized, controlled studies, especially for medications like HCQ with nontrivial levels of adverse events. I notice that most investigators publishing on clinical experience with hydrochloroquine shy away from either blinding or control arms like vampires backing away from garlic.
    They also usually publish in preprints, safely away from peer review (except for Raoult, et al, who have a friendly journal with an editor-in-chief who’s also a co-author of Raoult on the papers he cleared for publication), according to Retraction Watch and Elsevier, who co-publishes the journal in question).

    When the bulk of favorable clinical experience about a potent drug with a range of irreversible side effects is either published to the accompaniment of a really rank publication ethics scandal or published safely away from peer review, I think I’ll pass on it. Just as I would pass on chloramphenicol for either prophylaxis or treatment of COVID-19 despite arguably a smaller chance of side effects (although in that case, the side effect is aplastic anemia, irreversible, and lethal).

    I do supplement my and my wife’s zinc intake with known (or at least strongly rumored) zinc ionophores which happen to be legally-available “health supplements”. I am aware that at least 2/3rds of that expenditure is going through us into the toilet with no discernible improvement to our health, but it’s a gamble with no real downside.

  30. Anon says:

    Paper from 2011 in journal blood……” Hydroxychloroquine drastically reduces immune activation in HIV-infected, antiretroviral therapy-treated non-responders” ….Leftist scientists: ..”nothing to investigate here, Trump said it so it must be wrong”. ……The thing is it takes 2 seconds to read the science literature and figure out this thing has and had promise for COVID-19. I found this in under a minute using a simple google search. Can people not read or what? Trump derangement syndrome is very much real.

    1. m00 says:

      take a breather, must be exhausting seeing evil leftist boogeymen everywhere. Believe it or not, most of the world do not care all that much about Trump. Study you have quoted has no relevance to Covid.

      1. steve says:

        Pretty typical Trump supporter. Post completely irrelevant nonsense and claim that anyone who points out Trump’s ignorance is deranged. I’m sure that “fake news” and “Hillary’s emails” can’t be far behind.

        1. mike barnes says:

          What is all this. Here is the REAL Covid v. Hydroxy study by Leon Festinger, Henry Riecken, and Stanley Schachter et al (1956) (

          ….The spaceship is loading for Clarion with DJT at the helm, better get on board.

    2. Pajas says:

      Dude, cite your source. Also, reading an abstract in 2 secs does not equal reading a paper.

    3. drsnowboard says:

      Leftist scientists? Definition needed… if you follow the science, the evidence isn’t there. I’m not a statistician, I’m not an expert in ITT or powering of studies but to me, it just doesn’t hang together. There’s one camp that says you have to give it early , there’s one camp that says you dampen the immuno firestorm at a late stage. Can both be right or is it more likely that neither are?
      I’ll admit I’m european so not too interested in MAGA and so you can dismiss me. But my observation of your president is that he will do anything, say anything that serves him, his political ends and his family. Anything. I think he’s incredibly astute in a nakedly self interested way, he has surfed a political wave in a way no-one could have imagined. Do I rate his objectivity on hydroxychloroquine? No. I would say that makes me a scientist. Let’s hear form the rightist scientists .

  31. blogreader01 says:

    Most common reason for bashing Trump: He said something or did something/anything that made the news. Whether it’s HCQ-related or whatever else, if Trump did it, it’s unbelievably crazy, outrageous, misguided, mean, nasty, nefarious, etc., etc. Meanwhile, media credibility, per virtually all surveys, sinks lower and lower into the toilet. Lots of people outside of the anti-Trump echo chamber not buying in, perhaps? Methinks yes.

    1. Dennis Kleid says:

      Well, come on, the dose is way too low. Everyone knows that. If a little bit does not have any noticeable effect, then Trump needs to triple the dose. BTW, according to scripture, he will be taken away 42 months after taking power, which is July 2020. He must raise the dose or many many many of us will lose the beast.

    2. Gus Kantauskas says:

      Hmm, I wonder which of these 2 statements is more likely:
      – 90% of all world media, in different countries and continents suddenly uniting on an international conspiracy that Trump admin are largely a bit of a sh!t show
      – Trump admin is actually is a bit of a sh!t show…

  32. Sergio Valles says:

    Wish you guys/gals would stick to science instead of falling for propaganda. This reminds me of why we have book smart vs street smart. If you only believe what you are told to believe then it’s no surprise why you can’t think outside the box. It’s a was time, as I just want facts instead of biased viewpoints.

  33. steve says:

    The #1 indication that a hypothesis is bullshit – lots of ad hoc additions. Hydrochloroquine cures COVID! I mean Hydochloroquine PLUS Azithromycin! You didn’t add the Zinc! It’s Hydrochloroquine PLUS Azithromycin PLUS Zinc! The kitchen sink! You forgot to toss in the kitchen sink! It’s Hydrochloroquine PLUS Azithromycin PLUS Zinc PLUS the Kitchen Sink! Sheesh, why doesn’t anyone do it right?

    1. Charles H. says:

      And the real problem is that there *MIGHT* be an actual useful discovery somewhere in the combinatorial nightmare. But the chances of actually finding it are minimal, unless you are guided by a workable theory. Perhaps you need exactly some particular combination of ingredients in some particular proportion (which varies by which particular genetic alleles you have) in some particular amount (which varies with how much water you drink per day. Good luck finding that.

      So actual searches for treatments must be guided by useful theories. And useful doesn’t mean easily describable. It means theories that you can define ahead of time and make predictions based on. This won’t find all the possible interactions. But the search space is too large to search everywhere.

      1. Some idiot says:

        Agreed. And by theories you can make predictions with, I think the ability to falsify the theory is the most important. Science works best when something is put up on a stick where everyone can try and shoot it. If it is still there when the smoke fades away, it is probably pretty good. If it was hidden behind a concrete bunker: who cares? It wasn’t a useful theory anyway…

        And Occam’s razor is, in my opinion, one of the most important tools in the scientist’s tool kit… If the hypothesis needs too many add-ons, then it is best to go with a simpler explanation until/unless that is shown to be wrong. Keep it simple. Keep it falsifiable.

  34. Alan Goldhammer says:

    If HCQ is such a good prophylactic why isn’t the US military using it right now? Certainly, we have seen the problems of infection aboard the Theodore Roosevelt carrier.

    1. Some idiot says:

      Good question, and I think the short answer is that there has been no gold-standard clinical trials run on it that can answer the question. So we don’t know.

      Having said that, I read today that there is a 2250 subject, 4 month study which is placebo-controlled starting very soon amongst health personnel in Australia (they will all be screened for heart problems first). If the study works (and by “works”, look below…) it will be good to resolve the question one way or the other.

      Having said that, I actually have difficulty seeing that the trial will actually come up with a result (unless HCQ is incredibly effective), for the best possible reasons. Infection in Australia is now more or less under control, which means that the number of health personnel that are likely to contract it in the next while will be low, which means that there is probably a significant chance that it will probably be difficult to have sufficient infections (nice problem to have, though!) to get any sort of statistical significance.

      Unless, of course, it is incredibly effective. And yet even then…!

  35. Wendy says:

    Emmmmm, interesting. I am from Shanghai, I know HCQ is ranked the first choice in “Shanghai plan” therapeutic drugs. In Shanghai hospitals now, every patient who got infected by COVID-19 virus will be treated with the drugs.

    And why did the author incite an earlier Chinese study? The latest studies in China show HCQ efficiency against COVIDー19 on hundreds of patients.
    So I guess the author does not really care about the researches in China, does he?

    1. Derek Lowe says:

      I’ve referenced numerous Chinese studies in my various posts on hydroxychloroquine – if I’ve missed some, please provide some links to them. Thanks!

      1. Wendy says:

        Efficacy of hydroxychloroquine in patients with COVID-19: results of a randomized clinical trial

        Hydroxychloroquine application is associated with a decreased mortality in critically ill patients with COVID-19

        And this study is about the similar but more dangerous drug Chloroquine.It seems to work, too.

        1. Derek Lowe says:

          The first link you give was discussed here in this post:

          The second link you give was discussed in this post:

          I did indeed miss your third link – but note that it is a retrospective observational study that only features 10 patients who were treated with cholorquine, so it can hardly tell us anything at all.

          1. Wendy says:

            How about this one, written by the same lead author:
            “Preliminary evidence from a multicenter prospective observational
            2 study of the safety and efficacy of chloroquine for the treatment of
            3 COVID-19”
            A total of 197 patients completed chloroquine treatment, and 176
            92 patients were included as historical controls.

      2. Wendy says:

        I don’t know why I can’t reply you.

      3. Wendy says:

        OK, there are some papers on and, but everytime I post the links, my comments disappeared.
        So everyone can search “Hydroxychloroquine application is associated with a decreased mortality in critically ill patients with COVID-19”, authors are Bo Yu, Dao Wen Wang, Chenze Li.
        “Efficacy of hydroxychloroquine in patients with COVID-19: results of a randomized clinical trial”, writted by Zhaowei Chen,Jijia Hu, Zongwei Zhang, Shan Jiang, Shoumeng Han, Dandan Yan, Ruhong Zhuang, Ben Hu, Zhan Zhang

        And this study is about the similar but more dangerous drug Chloroquine.It seems to work, too.
        “Treating COVID-19 with Chloroquine” by Mingxing Huang, Tiantian Tang, Pengfei Pang, Man Li, Ruolan Ma, Jiahui Lu, Jingxian Shu, Yingying You, Binghui Chen, Jiabi Liang, Zhongsi Hong, Huili Chen, Ling Kong, Dajiang Qin, Duanqing Pei, Jinyu Xia, Shanping Jiang, Hong Shan

  36. SteveM says:

    This story illustrates the now raging American political dumpster fire.

    A rational, insightful President curious about Hydroxychloroquine would not have blurted out a royal statement of absolute clinical value of the drug. Rather he would have noted the positive anecdotal reports and then directed Dr. Fauci and his Task Force to oversee robust clinical trials of the drug and drug combinations. Those reports would have been available by now, so Dr. Lowe would not have to rely on other reports, many with design limitations.

    Too bad the “rational, insightful President” part of that scenario makes it completely infeasible.

    The other accelerant to the dumpster fire was the Trump Haters’ response. Trump was prescribed a drug by his physician who is well aware of the positive anecdotal claims as well as the side effect profile. It is also a generic drug safely utilized by millions for decades. Yet the Trump Haters blasted Trump’s decision by hyper-inflating the risk and inferring that Trump was doing little more than speed-balling Hydroxychroloquine on the side with no medical oversight.

    Whether you like Trump or hate Trump, Trump still has a right to contribute his own opinions and judgment related to his medical care in concert with his physicians.

    Bottom line: Trump brought this on himself by not ordering explicit clinical trials. (Because he’s too stupid and too arrogant). And the Trump Haters validated their contribution to the now out of control dumpster fire by hyper-inflating a private decision between Trump and his doctors into yet another worthless shouting match between dueling political hack factions.

    P.S. Stick a fork in America – because it’s cooked…

    1. Alan Goldhammer says:

      @SteveM – NIH is funding a number of HCQ trials.

    2. Hap says:

      It’s not that safe, though – the QT prolongation is significant. Its known effect against malaria (and other things) means that in those cases, it’s useful because its side effects are outweighed by its effectiveness. For COVID, though, its effectiveness isn’t known, and so because the potential side effect is so severe (with significant frequency of occurrence), it isn’t really a very good idea (it’s cheap, but there are better drugs to repurpose for COVID instead of HCQ).

      I think Trump banging on it got people’s ire up (and that may have been part of his intent – he likes owning the libs, and so…) and so the people like me who loathe Trump probably overreact. But using HCQ against COVID wasn’t a good idea when there wasn’t much data and it hasn’t improved with further data.

      1. SteveM says:

        Re: “It’s not that safe, though”

        That is a personal decision for YOU only. Trump has the same rights to make decisions related to his own PERSONAL medical care as anybody else. A licensed physician prescribed it. That same physician is no doubt following all of the required diagnostic protocols to identify any unintended coronary events.

        My aversion is Trump is unbounded, but there is nothing more unbounded than visceral Trump-Hate that creates mountains out of molehills.

        P.S. I wish the Trump Haters invested 1/10th the energy protesting Trump’s continuation of the TRILLION dollar Wars to Nowhere in the Middle East.

        I.e. Trump + Hydroxycholoquine => The Horrors! Trump + Iraq + Syria + Yemen => No Big Deal

        1. Hap says:

          Except a lot of the problem has been his general advocacy for it (as an alternative to doing things that have worked before to limit pandemics but will make it harder for him to get elected). If he can convince the WH physicians that it’s OK, then I guess it’s OK for him, but there are these things called data that are helpful in making risk-benefit calculations for other people.

          Ultimately, the HCQ sonata shows the problems with being immune to data and puts Trump’s immunity to it on display. That seems worthy of some contempt.

  37. Teukka says:

    As to other trials, have you guys and gals seen if anything can be dug up on the trials of HCQ done in one or two Swedish hospitals, Sahlgrenska University Hospital in Gothenburg and Karolinska University Hospital (can appear as the Karolinska Institute (the two are closely linked)) in Stockholm.
    From what I recall from local press coverage, they both did trials of HCQ, but had to pull the plug because they deemed the risks overweighed the potential benefits to such a degree that it wasn’t ethically defensible to let the trials go on.

    1. A Nonny Mouse says:

      That was with chloroquine, not hydroxy.

      1. Teukka says:

        From what I understand, the mechanisms of action appear to be the similar with both, but the HCQ has slightly less adverse effects. Also, the two substances being so similar, they would’ve switched from Chloroquine to HCQ if all that was at play would’ve been side effects.

  38. blogreader01 says:

    Not that it will be of much use to the pearl-clutching/hyperventilating/groupthinking cohort out there but here it is. A calm, reasoned message from a very credible source; a person who is simultaneously leading a well-designed study.

  39. tt says:

    Just so much wasted time, effort, and ink (digital) on a drug or combo that clearly hasn’t shown much promise (drugs with strong signal tend to stand out, even with weak studies). It was politicized immediately and now it is likely impossible to quickly do a definitive study due to the passions it ignites. This somehow went from a scientific question to a matter of belief and, as such, no amount of data or study will ever change the minds of the true believers. I respect Dr. Lowe’s patience in even posting about HCQ at this point, given the trolls and true believers it tends to attract. Myself, I’m far less charitable and just assume that there can be no rational discussion and analysis of whether there is a benefit, however slim, to the use of HCQ and all is combos. Living in the heart of NYC, I’ll just stick with what seems to be working: masks, hand washing, and social distance (with lots of take-out orders and deliveries to support local businesses). For now, we just buy ourselves some time because there is no miracle repurposed drug coming to save us, but we can at least delay the inevitable spread and cross our fingers for a vaccine. Whether the curve is sharp or flat, the sad reality is that the area under it is the same.

    1. Fix News and Friends says:

      Words of wisdom for everyone – thanks for a dose of sanity, in short supply these days. Thanks – stay safe tt/NYC.

    2. Charlotte says:

      Dr Paul Mariks protocol

      He is an intensivist and the inventor of HAT (hydrocortisone, Ascorbic acid, Thiamine) therapy for severe sepsis which got better outcomes than standard therapies used for treating life threatening sepsis

  40. RA says:

    I think what is at the root of all this is that there is a different way of looking at this from the scientific point of view and Trump’s political interest. From the scientific point of view, the jury is still out as to how this could be effective and in what stage of the illness or types of people…but the indications so far are that this is no game-changer and given the potential side effects, need to be careful and get the data.

    However, from a strictly political point of view, it makes a lot of sense for Trump to push this:

    1. The fact that most people either won’t get infected or get seriously ill from COVID AND most people who take the hydroxy/azithro/zinc cocktail won’t have adverse effects means that there will be a lot of people who would not have gotten sick and will credit trump for not getting sick, even though he had little to nothing to do with them not getting sick. Sure, some will get sick or get side effects…but they will be far outnumbered by those who don’t. Trump gets the credit in these voters’ minds for bravely bucking the system and promoting a medicine that didn’t do very much. The fact that republicans are disproportionately in lower population density areas with less structural risk of spread (and most who die will be in blue states) magnifies the political benefits to this. He just needs enough rural voters in swing states who were going to be fine anyway revved up and he wins.

    2. It allows Trump to deflect blame for the economy and body count (which will be discredited as fake news as well) –> i.e. if only they had listened to me on Hydroxychloroquine, the economy would not have crashed because of “liberal lockdowns”and many people would not have died.

    3. He knows that “liberal lockdowns” or not, the biggest impediment to economic rebound and his re-election prospects is people’s fear of venturing out and resuming activity. He needs as many people as possible to have the false sense of security provided by hydroxy/azithro/zinc to get out and resume economic activity so he can get the credit for a “rebound in progress.” That’s why he loves the guy in Long Island who was chasing a reporter saying “I have got hydroxychloroquine!” He gives a bunch of people, most of whom would not have gotten serious illness anyway, their invincibility pill. Most of them will never know that they might have set off a chain of transmission that killed someone through asymptomatic spread. They will be super loyal to him and turn out in the election.

    4. His base is already primed from a steady diet of conspiracy theories…the liberal scientist repressing a useful treatment trope plays right into that, and when scientists start to get political themselves, they play right into his hands! It’s all fake news to the average person!

    Basically, he is playing evil political chess while well-intentioned scientists and democrats are playing bleeding heart checkers…and why he is sadly likely to win. We play right into his hands by calling him dumb when he is playing much of the country rather effectively given how crappy of a hand he has. That’s why he is within stealing distance in the polls.

    I am not sure the right way to counter this, but the best I can think of is to call his bluff and demand that he visit the victims in a COVID ICU, where his formula of no masking and taking hydroxychloroquine/zinc can be put to the test. Or for scientists to facetiously “offer” to do challenge trials in Trump supporters taking hydroxychloroquine (AND ZINC!!!) …I mean, after all, it is such an emergency to get it out there and they are so convinced it works…maybe they can play rhesus monkey! Haha, of course, I jest and we would never do anything like that…but to me, that seems to the right rhetorical response…prove you believe your own BS…because I don’t think he really does…that’s why the white house now has masking, testing, and tracing…while we are fighting about hydroxychloroquine!

    1. tt says:

      Think of how stupid the average person is, and realize half of them are stupider than that.
      — George Carlin

  41. Truth9834 says:

    This thread is extremely biased focusing on anti-trump rather than on the real issue – does hydroxy (with zinc) help you? From what I have read, it “appears” that the hydroxy/azithro/zinc cocktail helps fight off the virus if taken early (as an anti-viral medication). The downside as pointed out by many is the possible arrhythmia from this drug combination. I don’t agree that hydroxy alone (with zinc) results in any arrhythmia problems as hydroxy has been used for many years with no arrhythmia issues. Studies show that once you are very sick that this drug combination does not help much other than possibly reducing a cytokine storm reaction from the virus and there are better drugs to take at that point. So the issues, at least for me, is (1) would I take this as hydroxy/zinc as a prophylactic; (2) if I was to get the coronavirus would I take the hydroxy/azithro/zinc cocktail or just hydroxy and zinc.

    With respect to issue (1) India offered HCQ prophylaxis to 10,000 Mumbai policemen. About 4,500 routinely took HCQ, while 5,500 refused. RESULTS: HCQ group: 0 deaths – Non-HCQ group: 9 deaths with those with who contracted COVID-19 in the HCQ group having “mild attacks” – answer I will wait for more studies.
    With respect to issue (2) – I will take hydroxy and zinc – it is safe and there is no down-side only up-side and the downside is significant (death).

  42. Truth9834 says:

    Correction – With respect to issue (2) – I will take hydroxy and zinc – it is safe and there is no down-side only up-side and the downside of the coronavirus is significant (death).

    1. Barry says:

      The published side-effects of hydroxychloroquine are not insignificant:
      Blistering, peeling, loosening of the skin
      blurred vision or other vision changes
      chest discomfort, pain, or tightness
      cough or hoarseness
      dark urine
      decreased urination
      defective color vision
      difficulty breathing
      difficulty seeing at night
      dizziness or fainting
      fast, pounding, uneven heartbeat
      feeling that others are watching you or controlling your behavior
      feeling that others can hear your thoughts
      feeling, seeing, or hearing things that are not there
      fever with or without chills
      general feeling of tiredness or weakness
      inability to move the eyes
      increased blinking or spasms of the eyelid
      joint or muscle pain
      large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, and sex organs
      loss of hearing
      lower back or side pain
      noisy breathing
      painful or difficult urination
      red irritated eyes
      red skin lesions, often with a purple center
      severe mood or mental changes
      sore throat sores, ulcers, or white spots on the lips or in the mouth
      sticking out of the tongue
      stomach pain
      swelling of the feet or lower legs
      swollen or painful glands
      trouble with breathing, speaking, or swallowing
      uncontrolled twisting movements of the neck, trunk, arms, or legs
      unusual behavior
      unusual bleeding or bruising
      unusual facial expressions
      unusual tiredness or weakness
      yellow eyes or skin

  43. Truth9834 says:

    I should have said the side effects are either “not common” or “very rare”. Remember you are comparing this to the coronavirus which may result in death, organ failure, heart attacks, etc. with odds that are so much higher that they should not be compared to this drug.

    Hydroxychloroquine Side Effects

    Not common:

    A Disorder Of The Retina Of The Eye
    Abnormal Function Of The Cornea In The Eye
    Corneal Opacity, A Scarring Disorder That Results In Clouding Of The Cornea Of The Eye
    A Skin Rash
    Bleached Hair
    Blurred Vision
    Decreased Appetite
    Discoloration Of Nail
    Discoloration Of The Mouth
    Hair Loss
    Skin Discoloration

    Rare side effects:

    A Disease With Shrinking And Weaker Muscles Called Myopathy
    A Disorder Of The Peripheral Nerves That Enable Movement Called Peripheral Motor Neuropathy
    A Skin Disorder With Blistering And Peeling Skin Called Stevens-Johnson Syndrome
    A Skin Disorder With Blistering And Peeling Skin Called Toxic Epidermal Necrolysis
    A Type Of Abnormal Movement Disorder Called Dyskinesia
    A Type Of Allergic Reaction Called Angioedema
    A Type Of Significant Allergic Skin Reaction Called DRESS Syndrome
    A Type Of Skin Disorder Called Acute Generalized Exanthematous Pustulosis
    Abnormal Liver Function Tests
    Abnormal Muscle Movements
    Acute Liver Failure
    Cardiomyopathy, A Disease Of The Heart Muscle
    Changes In The Visual Field
    Decreased Blood Platelets
    Deposits On The Eye
    Erythema Multiforme, A Type Of Allergic Skin Reaction
    Extrapyramidal Disease, A Type Of Movement Disorder
    Fluid Accumulation In Cornea Of The Eye Causing Swelling
    Hearing Loss
    Heart Failure
    Increased Sensitivity Of The Skin To The Sun
    Low Blood Counts Due To Bone Marrow Failure
    Low Blood Sugar
    Low Levels Of A Type Of White Blood Cell Called Neutrophils
    Low Levels Of White Blood Cells
    Mental Problems From Taking The Drug
    Mood Changes
    Muscle Wasting
    Muscle Weakness
    Pigmentary Retinopathy
    Prolonged QT Interval On EKG
    Skin Rash With Sloughing
    Suicidal Behavior
    Torsades De Pointes, A Type Of Abnormal Heart Rhythm
    Ventricular Arrhythmias, A Type Of Abnormal Heart Rhythm
    Very Low Levels Of Granulocytes, A Type Of White Blood Cell
    If experienced, these tend to have a Less Severe expression
    A Change In Vision
    Acquired Chromatopsia, A Change In Color Vision
    Decreased Vision At Night
    Intense Abdominal Pain
    Loss Of Muscle Coordination
    Low Energy
    Muscle Tremors
    Nystagmus, A Condition With Involuntary Eye Movements
    Ringing In The Ears
    Sensation Of Spinning Or Whirling
    Visual Sensitivity To Light
    Weight Loss

    1. RA says:

      Interesting news story from Mumbai, assuming the numbers are right, one wonders if the police officers who declined Hydroxychloroquine had some reason for doing so (heart problems?) that could be one of many confounding factors. The studies for pre-exposure prophylaxis are in progress so we shall see!

      What you are asking in your 2nd point is post-diagnosis treatment. And your reasoning is that the risks of COVID are higher than the risks of the drug in that scenario….but I think it would be hard to make a blanket statement on the limited data so far. We would need data to help guide us to make decisions based on a number of factors:

      1. Your age, underlying conditions and other risk factors for severe covid disease vs your risk for hydroxychloroquine complications (do you know your Qtc interval at baseline?).
      2. How early in the course of the infection are you?
      3. How sick are you? Asymptomatic positive? Mild symptoms? Severe Symptoms?
      4. What setting are you in? Are you taking this at home or in the hospital while attached to a cardiac monitor?

      Depending on all these factors, the benefit of Hydroxy/zinc (if there is any) vs risk of side effects could vary for specific patient scenarios. We just don’t have the data for most of the potential scenarios out there yet, and varying clinical judgments and somewhat informed trial/error methods are what are being used in the clinical setting now. I know, uncertainty sucks, big time!

      Which is why the most rational thing to do is to do whatever you can to avoid being the guinea pig who gets COVID while the data is still preliminary and crappy…i.e. prevent infection in the first place…if you cant stay home, make sure everyone around you is wearing a mask properly…like President Trump is now when the cameras are not on! Be like Trump in that way everyone!!!!

      1. Truth9834 says:

        You can try the Nick Cordero standard care treatment and hope for the best though it did not work out well for him (Cordero, 41, has battled a series of coronavirus-related complications since he was hospitalized in March. He spent weeks on a ventilator and had to have his leg amputated after clotting issues and his condition is getting much worse), or you can be proactive and take this medication (with zinc) before your illness becomes life threatening. Remember there are more than a few cases where one showed mild or no symptoms and then all of a sudden within a day or two they were very sick. Why is that? The virus is in your body multiplying and your body is not fully aware of the problem. For example, this can happen where the virus starts deep in the lower lungs and the body does not show any or it shows minimal effects of this virus until it is too late (blood clots are another example). So I would not rely on mild symptoms to determine if I should or should not take this medication. At the very least if you use this mild symptom approach get a pulse oximeter and watch your oxygen level as low oxygen saturation levels are a sign of a deteriorating condition. Clearly if you are over 50 you should consider taking the hydroxy (with zinc) at the first sign of this illness or if you have high blood pressure, a BMI over 30, diabetes, etc. Most importantly consult with a doctor before taking this medication. As a side note all of my doctor friends and I are in complete agreement that hydroxy with zinc is the best treatment approach at least as of May 20, 2020.

        1. RA says:

          I agree with you that we want to be able to intervene earlier in the course of the disease….and I happen to think pulse oximetry is probably wise and I also wonder about anti-coagulants early in the milder, non-hospitalized disease…what is the risk/benefit ratio there? We all should be talking more about these issues and doing the science to clarify them and improve care as well as improving the health care delivery systems to make them happen (i.e. more rapidly available and resulted testing)

          Your approach might be reasonable for certain patients…having an open mind and letting the data guide us will be critical. And in the absence of data, consulting with a physician to make individual treatment decisions is indeed critical…keeping in mind that we are operating with limited evidence and so we could be wrong. We need far fewer self-proclaimed experts and much more intellectual humility in the face of a new disease with much yet to learn.

          Intellectual honesty would dictate, however, that there might be clinical scenarios in which hydroxycholorquine/zinc does more harm than good…i.e. if say you are a young female who tests positive with mild symptoms but has an elevated, undiagnosed Qtc…is your better move to take a QTc prolonging med or not when your risk of progression to more serious disease might be lower than the risk of prolonging your Qtc further and going into a fatal arrhythmia (that I now term Torsade de Trump)? Maybe you are confident you know the answer, but I am not!

          Many people are looking out for numero uno right now, but since this is a societal wide problem, the other consideration for people who care about public/population health is how any intervention affects spread. Do any of the folks who think the data is sufficient for a personal anti-viral benefit to hydroxychloroquine think it makes you uninfectious and absolves you of wearing a mask around others? Because there are some people who will interpret it that way…case in point:

          So can those of you pushing this cocktail we modify it just a bit more…Hydroxychloroquine/Zinc/Mask?!?!? Please!?!?!

  44. R. Eric Billings says:

    There is another problem with President Trump’s Hydroxychloroquine cheer leading – much like the hand sanitizer and toilet paper supply chain, the medicinal supply chain was not really expecting a surge in demand for HCQ. It can ramp up, but it takes time.

    The impact is that patients who were on prescriptions for HCQ for non-COVID reasons (for example: Lupus) are now facing shortages.

    I keep coming back to the thought that this HCQ addiction epidemic is the new Opioid epidemic. It took years for the legal system to punish Dr. Kapoor for his actions.

  45. Nada Nemo says:

    You know, with everything going on, I sometimes find myself wishing that there would be a blog post about a chloroquine derivative festooned with lots of nitrogens and fluorines or iodines, under “Things I won’t work with.”


    1. angrygecko says:

      What this drug needs are more peroxides.

    2. loupgarous says:

      Mefloquine’s got six fluorine atoms hanging off of its structure and a bad rep among soldiers who have to take it for prophylaxis against malaria. FDA’s blackboxed it for late neuropsychiatric problems that can appear long after the patient stops taking mefloquine. That bad enough for you?

      Maybe Derek can start a new topic category here – “Drugs I Won’t Take”.

      1. A Nonny Mouse says:

        We developed a cost effective process to the individual isomers of mefloquine (and a low cost process as well, by accident) which was funded by the WHO. The expectation is that the CNS effects of the more potent isomer would be reduced. Unfortunately, this isomer was metabolised more rapidly and required higher dosing which negated the positive effects!

      2. Druid says:

        The dosing advice to travellers for prophylactic use of mefloquine is to start 1 week before travelling. That means taking the second dose on the day of travelling. The hypoxic effects of high-altitude on drug metabolism are little studied. There are many behavioural studies but I cannot find a PK study of mefloquine in hypoxia (anyone?), but what evidence there is for other drugs supports the idea that travellers have reduced clearance while airborne and overdose on mefloquine. My advice is to start treatment a few days earlier and take the third dose after landing instead of before take-off.

  46. John says:

    I’ve continued to follow Dr. Didier Raoult’s interviews on video. He seems to give youtube presentations every Tuesday. In his most recent video, Raoult makes three interesting points:
    1) The Covid infection rate in the Marseille region has dropped to near zero.
    2) The death rate from Covid in the Marseille region is 1/5 that in the Ile-de-France region namely, Paris (where they are not using the HCQ-Azithromycin treatment approach).
    3) When one looks at deaths by age group, in both China and in the Paris region 50% of the total deaths have been in persons <70 years of age. In Marseille, there are almost no deaths in patients 70.
    Of course this is only indirect evidence for a potential advantage for the Marseille approach to diagnosis and treatment.
    Turn on closed captions and summary. You can then use the You Tube summary function to capture the translation and then use Google Translate if your French is rusty

  47. John says:

    Intended to write:
    In Marseille, there were almost no deaths in patients below age70.

  48. thxzetec says:

    I am somewhat pro chloroquine and this post seems anti, but well written thanks. Also interesting reading the comments.

    No there has not been a “golden” study (random, double blind, big-enough, etc) to show with confidence this drug works – but also no such study showing it does not work. I’d like to see such a study 1) w/ zing 2) given to people when they become ill, not at serious phase of disease.

    It is interesting to compare to remdesivir (?). Where chloroquine is public iP and inexpensive Remdesivir is patented and likely much higher cost. I am **not** drinking the rapid anti-pharma koolaid here, I believe it has some benefit. What i am saying is that Remdisivir had wealthy company that would benefit, so maybe more likely to get high-quality study.

    1. tt says:

      Wrong…Gilead is donating the drug (free), but I think it is in the same state as HCQ in that there is no good data showing it has any benefit.

  49. ursobr says:

    Are you aware of the big political issue that chloroquine and hydroxychloroquine have become in Brazil? Far-alt-right President Jair Bolsonaro is very aggressively pushing for generalized chloroquine use even in the slightest suspicion of COVID-19. Two health ministers have been sacked in less than one month, in part because of their refusal to endorse mass chloroquine use against scientific evidence. The government has bought millions of doses for distribution and the interim new minister (a military officer with no biomedical or scientific background whatsoever) has already published a new official COVID-19 treatment protocol using chloroquine all the way. Doctors are in a conundrum, afraid that they might be sued if they don’t prescribe it, but also sued if they do and the patient has serious side effects. Meanwhile, ministers more in line with the President are touting chloroquine as a “miracle cure” for COVID-19 (and they are using these exact words!).

    Bolsonaro has said that COVID-19 is “hysteria” (his foreign minister published an article saying that the COVID-19 “myth” is part of a Communist plot to take over international organizations, starting with the WHO!), that it’s “no more than a little flu,” that social distancing and lockdowns are folly and everybody should be working normally (mayors and state governors are trying to enforce partial or total lockdowns, though), and replied “so what?” when a reporter asked him about the growing number of COVID-19 deaths in Brazil (as of this writing, Brazil is the 3rd country with the greatest number of cases and the 6th in number of deaths, with almost 300,000 and 20,000 respectively, but considering the extremely low testing rates and widespread underreporting, real figures are likely to be much more — up to 15 times more, according to an estimate from a university in Southern Brazil).

    The “rationale” (if it can be called that) behind Bolsonaro’s obsession with cloroquine is not totally clear, but it seems to stem both from his well-known contempt and despise of science and from the wish to see economic activities resume as soon as possible, because he fears he will not be re-elected if the economy is bad. The next presidential election will only be in late 2022, over two years from now, but with over 30 petitions for Bolsonaro’s impeachment pending in the Brazilian Congress and Supreme Court for other reasons, he’d rather be on the safe side. His popularity is falling, but there is a hardcore stubborn group of fanatic supporters to whom he is a god, and that makes up about a third of the population. Things are going to get very chaotic in Brazil in the next months, and chloroquine is going to play a significant supporting role in this chaos affecting the country’s 210 million people.

    1. John says:

      There’s a lot of spin about country data mortality for COVID. I have been going to the IHME COVID-19 site for actual data, ignoring their projections, which I think are not very meaningful, focusing on actual reported daily deaths to-date. You can go to:

      and scroll down to “daily deaths”

      Then there is ‘compare’ function, and you can select Sweden (differences vs. U.S. are underwhelming) or Brazil (differences so far are also underwhelming). The projection is, that Brazil will get worse and the U.S. will get better in the coming monhts, but the actual data shows no difference, other than a later start for Brazil.

      1. tt says:

        I think you are making a huge assumption that countries, states, and municipalities are all reporting deaths accurately and honestly. In the case of Brazil, those numbers are meaningless and certainly wrong. In the US, I would trust the NYC numbers (they report confirmed and also suspected, segregated out). Not to mention the permanent disability and harm caused by the infection recovery as well as people who are dying (heart conditions, cancer, etc) because they fear seeking out medical help due to risk of infection.

    1. SteveM says:

      Re: “A woman who took hydroxychloroquine for 19 years for lupus has tested positive for SARS-CoV-2.”

      So? Why did you waste time even posting this? What is the point?

      The larger subtext is that no matter how much of a vulgarian idiot Trump is. He deciding to take Hydroxychloroquine under a doctor’s supervision is nothing more than noise. Because it was his personal decision that had ZERO impact on anybody else.

      It’s noise that has been hyper-amplified by Trump Haters so consumed by their contempt, they lose total sight of the bigger picture.

      The U.S. under Trump flushes Trillions of taxpayer dollars down the toilet playing the Global Cop Gorilla with its War Machine, the tax code is a pathological train wreck, scores of cities and huge regions of the U.S. are economically bombed out, saturated with massive unemployment, learned helplessness and drug addition, Trump is blindly teeing up a total economic war with China suffused with negative knock-on effects and unintended consequences, per capita U.S. health care costs are 80% higher than other advanced countries. Among other things…

      Yet the Trump Haters froth frenetically about Trump and Hydroxychloroquine, as if that has any real meaning in the grand scheme of things.

      The perverse irony is that the Trump Hate that ignores what really matters may actually be what gets him re-elected.

      1. Some idiot says:

        Just to state things clearly: I am not here for the politics, I am here for the science. I do not live in the USA, so therefore I quite reasonably do not have a say in their presidency.

        But to Steve’s comment… The question has arisen a number of times (I don’t remember it in this blog post/comments but it has certainly cropped up earlier a number of times) that if HQC works profelactically (probably spelt this wrong, but whatever…) then there may be a signal in the relative rates of infection of people with lupus who take it, compared with those who don’t. Now, granted that (a) there are probably other confounding factors, and (b) this is only one data point, but it is interesting to know. And I presume that this is why Steve posted it. And I presume as well that all/most other regular readers would have come to a similar conclusion.

        So that’s my take on why he bothered to post it. Not more, not less. Spreading light, not heat.


  50. JJM says:

    Time to stop the madness – Aspirin and Tylenol are more dangerous that Hydroxychloroquine

  51. Miles says:

    Oh boy, Derek, you stuffed the starving komodo dragon into a bag with a dozen chihuahuas this time!

    1. cynical1 says:

      Many thanks for this one post. It made it worth reading the others………almost.

  52. Magrinho says:

    I scroll to the bottom of these threads with trepidation but I can’t help myself. There must be a corollary to Godwin’s Law that states that as the thread lengthens, the probability of reading a rabid, ad hominim attack approaches 1.

    Why is it necessary for some who post to draw a hard line of FOR/AGAINST when it comes to scientific questions/topics. It’s science, not politics. Be grateful.

  53. John says:

    One issue that impresses me is how cardiologists are looking at the QT prolongation risks with HCQ. For example, there is one recent paper in JAMA Cardiology by Mercuro et al
    where they looked at QTc changes in patients with COVID-19 treated with either HCQ alone or with HCQ + Azithromycin. Mercuro et al conclude:
    “CONCLUSIONS AND RELEVANCE In this cohort study, patients who received hydroxychloroquine for the treatment of pneumonia associated with COVID-19 were at high risk of QTc prolongation,”

    Aside from the fact that they did not report on QTc changes in a control group who were not treated with either HCQ or the combination, if you go to their data and look at the the left side of the figure, Figure A (hydroxychloroquine alone), you see that QTc in the COVID-19 patients treated with HCQ only went up in about 10 cases, but went down in 8.

    The baseline QTc was 474 msec, and the overall mean change was only 5 msec. Those of you who have analyzed scientific data know that, when you have a situation where close to 40% of a change is in one direction, and 60% in another, it is impossible for the change to be statistically significant. Incredibly, the authors don’t apply any statistical tests to the change in QTc in the HCQ only group.

    So, their conclusion of QTc prolongation with HCQ alone is not at all supported by their data! Even in supposed “top-tier” journals, it seems like group-think is holding sway over careful scientific analysis of data.

    Granted, by the way, that the combination, HCQ + azithromiycin (the right panel in the same Figure) does increase the QTc. The QTc prolongation effects of azithromycin are well known, though the clinical importance of this apparently remains a matter of debate.

    1. RA says:

      Direct quotes from that paper:

      “Of 37 patients receiving hydroxychloroquine monotherapy, 7 (19%) developed prolonged QTc of 500 milliseconds or more, and 3 (3%) had ΔQTc of 60 milliseconds or more.”

      “Within a 4-week observation period, 21 of 90 patients (23%) treated with hydroxychloroquine or hydroxychloroquine plus azithromycin had either significant QTc prolongation or ΔQTc of 60 milliseconds or greater. This underscores the American College of Cardiology’s recommendation for baseline risk assessment, frequent QTc monitoring, and strict cutoffs for therapy cessation”

      “It remains possible that the true degree of QTc prolongation was underestimated, given clinical practice variation and a limited follow-up period: 45 patients remained hospitalized, and 19 patients had no follow-up electrocardiograms. ”

      “Higher-risk groups may not have been represented, because institutional guidance recommended against hydroxychloroquine for individuals with prolonged baseline QTc intervals.”

      And the conclusion is…

      “Patients who were hospitalized and receiving hydroxychloroquine for COVID-19 frequently experienced QTc prolongation and ADEs, including a case of torsades de pointes with the administration of hydroxychloroquine and azithromycin, which to our knowledge has yet to be reported elsewhere in the literature. There is a critical need for rigorous, large-scale studies and risk-benefit assessment prior to initiating COVID-19 therapeutics, with careful attention to medication interactions, cardiac manifestations, routine electrocardiograms, and electrolyte monitoring.”

      What exactly in the conclusion is “group think” you disagree with? Can you be more specific with regards to the actual words in the conclusion paragraph that you think are unjustified by the data? Perhaps you could offer a suggested rewrite of that paragraph based on your perception of what is scientific?

      1. It may be a good time to talk about what QTc is.
        The QT interval, measured on the surface electrocardiogram, is related to the ventricular repolarization time. The ventricular wall is actually heterogeneous, and its layers don’t always repolarize synchronously. Prolongation of the QT interval usually (not always) reflects delayed repolarization of one layer much more than the others. This is important because arrhythmias said to be associated with pronged QT intervals are more accurately described as being associated with differences in repolarization state between adjacent layers. There are drugs that prolong the QT interval but that are actually antiarrhythmic (phenobarbital is the best-known example). There are a variety of congenital long-QT syndromes, all of them associated with arrhythmias, but there are also (rare) congenital short-QT syndromes, associated with arrhythmias that have the same genesis in layerwise heterogeneity of repolarization.
        Increasing concentrations of some drugs (notably including quinidine, a non-distant relative of certain drugs now in the news) monotonically prolong the QT interval, but their proarrhythmic risk is non-monotonic, because of differing effects on different myocardial layers.
        It’s not trivial to decide when the QT interval is prolonged, because as the heart rate increases, the QT interval normally shortens, somewhat less than linearly. On the basis of observations in a few dozen patients, Bazett decided that the QT decreased proportionally to the inverse square root of the heart rate, so he defined the QTc as QT/sqrt(heart rate in Hz). If this fit were correct, then computing your QTc at any heart rate would predict what your QT always was when your heart rate was 60 (that is, 1 Hz). In the same way, computing your BMI purports to tell how much you would weigh if your height were one meter.
        Now, the problem is that the Bazett formula isn’t very good. Literally dozens of competing formulas have been put forward over the years, because — as one might guess — there is no correct formula. The QT/HR relationship varies from person to person. Just limiting the discussion to power-law formulas similar to Bazett’s, the various published formulas have had exponents ranging from below 0.2, through 0.33 (Fridericia’s formula, now fairly popular), 0.5 (Bazett) to around 0.6. The Bazett formula is built into many old ECG machines, but it is no longer respectable.
        If a drug might be associated with changes in heart rate, serious QT investigations require lots of data from each subject, so that his or her personal QT/heart-rate relationship can be determined off drug.
        I bring this up because the Mercuro team used Bazett correction. Their results may be sound, but maybe not. For example, their baseline QTc of 474 ms would already be in the abnormal range, if it were reliable. But it’s a Bazett result, so it isn’t.
        For details, there’s an overrview in Fenichel, Robert R., Malik, Marek, Antzelevitch, Charles, et al. Drug-induced torsade de pointes and implications for drug development. Journal of Cardiovascular Electrophysiology. 2004; 15(4): 475-495.

        1. RA says:

          Thanks for that explanation…I learned a lot! It would seem that the authors’ call for “rigorous, large-scale studies” is right on track given how hard of a measurement issue there is here on which a lot of people disagree on the correct methodology. Hopefully more definitive work is in progress!

  54. Isaac Machado says:

    How can an antimalarial be effective in the treatment of COVID-19? Rufigallol (antimalarial) with less side effect based on Gallic Acid could be more effective. Why not gallic acid itself because it has antiviral, anti-inflammatory, anti-cholesterol, immunomodulatory, antiulcer activity and even neuroprotective, cardioprotective, hepatoprotective and nephroprotective potential, associated with other compounds can be an effective strategy to reduce hospital stay, as described below:

  55. John says:

    Sure, glad to be of help.

    The first line of their conclusion, and in fact their main conclusion is:

    In this cohort study, patients who received hydroxychloroquine for the treatment of pneumonia associated with COVID-19 were at high risk of QTc prolongation,”

    Note that this statement is written in a very strange way. The purpose of the paper would be, to see if HCQ alone, or HCQ + Azithromycin, prolonged the QTc.

    This first sentence of the conclusion, implies that HCQ use resulted in QTc prolongation. Agreed, they didn’t actually say this, because it was not true.
    Their data regarding QTc was not statistically significant. So, a normal person doing the study would say: “HCQ use was not associated with QTc prolongation.”
    This is a fair statement of their results.

    Now, the next issue is, going above 500, and a delta of 60 milliseconds or greater. Here the question is one of measurement variance. QTc is a complicated, derived measurement, as it has to be adjusted for the heart rate, and there is a fair amount of controversy about the best way to adjust for heart rate.

    No data is presented with regard to measurement variance. We know, overall, there there was no change in QTc in the HCQ group. Now, if the within patient variance is high,
    of course, there will be times when QTc goes up a lot, and there will be other times when QTc goes down a lot. This (terrible) paper never discussed on how many occasions in a given patient the QTc was measured. So, if I have a repeat measures coefficient of variation of 10%, and my baseline is 475 msec, of course at some point in time, it is quite likely that my QTc may be measured to be more than 500. This is meaningless without information about withn patient variability, and in the absence of averaging.

    What if the baseline QTc were 499 msec? You could take 100 patients, with no net change in QTc, and 50% of the time, QTc would go over 500. The baseline QTc of 475 msec was close enough to 500, such that the number of times a single, or “maximum” measurement exceeds 500 msec is meaningless.

  56. John says:

    To RA

    A bit more explanation might be in order re the conclusions of the Mercuro paper.

    Let’s do an example. Baseline blood pressure for a study group is 140/90. Target blood pressure is 120/80. You give the 100 patients fabulopril, a great anti-hypertensive. Unfortunately, after 3 months, the average blood pressure is 138/88, p = 0.80.

    However, in 30% of the patients, the blood pressure decreased to within the target range, less than 120 mm systolic. And in 20% of the patients, the drop in systolic blood pressure was > 30 mm Hg!

    Is fabulopril a good anti-hypertensive? Most would say, no, because there was no statistically significant change on the blood pressure on the group overall. Talking about how often the BP decreased to target, or how often the BP decreased by more than x mm Hg is, in my opinion, not useful. The fair reading of the results is, that fabulopril had no significant effect on blood presure. Similarly, the fair reading of the Mercuro et al results is, that HCQ had no significant effect on the QTc interval.

    1. RA says:

      Thanks for your explanation! I think like many early-stage retrospective studies being put out there in the fog of a pandemic, this has limitations like you mentioned. It’s probably under-powered too. But I am having a hard time finding evidence of some sort of “groupthink” here when the next sentence of the abstract conclusion you quoted is: “Clinicians should carefully weigh risks and benefits if considering hydroxychloroquine and azithromycin, with close monitoring of QTc and concomitant medication usage.” In the body of the paper, the last sentence is “There is a critical need for rigorous, large-scale studies and risk-benefit assessment prior to initiating COVID-19 therapeutics, with careful attention to medication interactions, cardiac manifestations, routine electrocardiograms, and electrolyte monitoring.”

      They are not saying that you shouldn’t use hydroxychloroquine…just be careful about it at this stage and we need more data. Seems like a pretty balanced and prudent message to me!

  57. Robert R. Fenichel says:

    “pronged” should be “prolonged”

  58. John says:

    To RA:
    Perhaps my group-think statement was unnecessary. I look at the data first, and what bothers me about the Mercuro paper in JAMA Cardiology, all else aside, is that their primary finding re use of HCQ alone in treating COVID-19 patients on QTC was NEGATIVE. Here are their data (I posted this earlier, but maybe it was disallowed for some reason: The data are taken from the left panel of their Figure A (HCQ only)

    QTc interval
    530 490 -40
    520 502 -18
    495 595 100
    485 540 55
    490 523 33
    485 477 -8
    480 475 -5
    478 498 20
    475 442 -33
    473 440 -33
    475 425 -50
    470 425 -45
    472 480 8
    465 480 15
    460 525 65
    460 500 40
    455 480 25
    453 435 -18
    425 430 5
    415 420 5
    Average 473.05 479.1 6.05

    When scientists report data in a paper, the first thing they do is subject the result to statistical evaluation: Is the change statistically significant?

    If you run a Paired T-test on their pre vs. post QTc data above the P value is 0.501. This is MILES AWAY from the required significance value of 0.05. So, their results showed the exact opposite of what they claim. In COVID patients treated with HCQ alone, there WAS NO SIGNIFICANT INCREASE in the QTc interval. The authors were being disingenuous in that they never reported subjected their data to any test of statistical significance in terms of pre vs. post. The only test they did was to compare the delta QTc in the HCQ + Azithromycin vs. HCQ only arm.

    In the HCQ + azithromycin group (right panel of the Figure in Mercuro et al), there was a significant increase (not reported in the paper) and there was a significant difference in the change in QTc on the HCQ + azithromycin vs. HCQ only arm.

    I was very disappointed by the sloppy level of review of this paper by JAMA Cardiology and the journal editor.

  59. Ken Nelson says:

    I understood why he mentioned this treatment early on. I just wish he hadn’t because of the reaction the press and large parts of academia have to him.

    I’m a computer scientist, so this is definitely not my area of expertise. I did examine the COVID source code and found it shockingly poor.

    It’s sad how science is so politicized that we can’t trust most science reporting, and as in climate, much of the actual science itself. How would future funding go for a pro-hydroxychloroquine study’s author? Or would peers review it? Would journals even accept it? The original proponent of the treatment had his life unwound in the NY Times. I’m dubious it will ever get a fair shake now that Trump touted it, and has now used it.

    Your blog is a rare treat – thanks very much.

  60. RA says:

    Thanks, I see what you are saying. They did sort of imply the nonsignificance in the overall results abstract by including an IQR that crosses 0 “…compared with those receiving hydroxychloroquine alone (5.5 [−15.5 to 34.25] milliseconds” But you are right, they didn’t report out an actual statistical test in the hydroxy only group. With your method, the p value is .501…so there’s basically a 50-50 chance that there is an overall difference based on this small sample of hydroxychloriquine alone. Doesn’t tell you much! But… I don’t know if you need a statistical value to tell you that a 5ms overall change is not clinically significant, so who cares if it is statistically?

    BUT…. how useful is an overall change statistic in a small group of heterogeneous patients? Could it not be possible that there is a subset of patients for whom hydroxy alone increases the Qtc to a clinically significant degree (if a study could get the complex measurement issues sorted out) and many others who are not affected, making an overall pre-post statistical calculation in a small sample not the best way of looking at it? From a clinical point of view, even if it is only, say 20% of patients who might have an elevation, I would think you would still want to know that so you can monitor it on those patients…not say those patients don’t matter because the pooled qtc overall change is not significant.

    It seems to me you would want a much bigger sample so you could dive deeper in the hydroxy only group and look at what clinical characteristics predicted the patients who did have larger Qtc changes (assuming they are measured “well”) and which characteristics predict those who do not). But obviously, we are limited in our data available at this stage so we read tea leaves!

    Maybe if this study were framed more as a large case series rather than a cohort study and was a bit more measured with language in some places, it wouldn’t fall so far below the expectations you have for it…but at the end of the day, I think the authors’ call for caution and more data are appropriate!

  61. John says:

    To RA:
    Thanks. What set me off is, that there are bloggers and journalists who are citing this study as evidence that HCQ is ‘dangerous’ therapy that may cause serious arrhythmic heart problems. I do believe that HCQ even in healthy patients, can cause a slight prolongation of the QTc interval which is not of great clinical significance.
    In studies like the Mercuro et al paper, there are so many variables. R. Fenichel raises an important point about heart rate. It’s one thing to find a QTc interval of say, 460 ms when the heart rate is 80, and then after giving a med or doing an intervention, find that the QTc has increased more than 500 ms at a similar normal heart rate. Quite a different issue if one is comparing a baseline heart rate of 80 with a heart rate of say, 120 or more when the patient is on a ventilator or in ICU. I would like to have seen some analysis of QTc vs. heart rate at baseline in these patients, and then delta QTc from baseline to end-study plotted against delta heart rate. Very simple, basic sorts of analyses. The authors talk about a QTc-max. There is no granularity given as to how often the QTc was measured. If you measure something a sufficient number of times, and look at the maximum difference, I think it’s pretty clear that you will be overestimating the true difference as you will be measuring measurement error more than biologic effect.
    Next, there was no control group. When patients get admitted to ICU they have all sorts of issues, that might prolong the QTc, including hypokalemia, hypoxemia, and I believe that myocardopathy has been documented with COVID-19. So, the absence of a control group makes it near impossible to say whether or not taking HCQ caused or magnified any increase in QTc in some “susceptible” patients, or if the increase was due to some other cause. Remember, that if the net change in QTc is zero, then in 50% of patients the QTc will be increased. Looking at subgroups is fraught with danger, even when these are prespecified. The authors point out that they found that diuretic usage (possibly via depletion of K stores?) and other factors such as ICU admission were involved in lengthening the QTc. There is no way to know if these factors have been modified or magnified by taking HCQ.
    This type of shoddily done study, accompanied by handwringing editorials from the journal editor, that extreme caution must be used, etc. when giving HCQ only serves to frighten people. I suppose some bit of scariness is useful, but as an example, I was reading David Boulware’s twitter feed, that when some of these scare messages were issued by the FDA, it became much more difficult to recruit patients for their RCT (early treatment and post-exposure prevention).
    It’s pretty clear from this study, that the QTc was increased from the combined use of HCQ and azithromycin. But this is nothing new. There was a study published in NEJM a few years ago that caused a big fuss, as there was a small increased risk of sudden death in patients treated with azithromycin compared to amoxicillin. However, when compared to ciprofloxacin, there was no increase in risk, suggesting that more serious conditions may have been treated with azithro or cipro vs. amoxicillin. Also, I believe that there is some evidence (my knowledge of cardiac electrophysiology is limited), that azithromycin increases QTc by acting on a different cardiac ion channel than the one affected by HCQ, and that the risk of torsades as a result is not as great as with some other meds that increase the QTc. I think I’ll leave it at that.

  62. No good news for the HCQ fan boys and girls. The Lancet published the largest observational study to date: Money Quote: We were unable to confirm a benefit of hydroxychloroquine or chloroquine, when used alone or with a macrolide, on in-hospital outcomes for COVID-19. Each of these drug regimens was associated with decreased in-hospital survival and an increased frequency of ventricular arrhythmias when used for treatment of COVID-19. One major critique is they don’t have any data on the use of zinc. Maybe that is the magic potion for efficacy

  63. Robert says:

    New publication in The Lancet, dated May 22, 2020 (online). Summary: “In this large multinational real-world analysis, we did not observe any benefit of hydroxychloroquine or chloroquine (when used alone or in combination with a macrolide) on in-hospital outcomes, when initiated early after diagnosis of COVID-19. Each of the drug regimens of chloroquine or hydroxychloroquine alone or in combination with a macrolide was associated with an increased hazard for clinically significant occurrence of ventricular arrhythmias and increased risk of in-hospital death with COVID-19.”


    1. Sanych says:

      For some reason, the study published in lancet did not include zinc.

      1. Jinhui Chen says:

        I read the report too. It’s a very lousy research.

  64. Jinhui Chen says:

    I can read that you aren’t politically neutral but hold an anti-Trump tone to write the blog posts. When people show you articles, you attack they aren’t creditable. By following your logic, we all know even the peer-reviewed journals often report fake/falsified data, make wrong and misleading discussion. When science infiltrated with political agenda, the credibility is lost just like the mainstream media.
    I will read every reports, news or scientific publication, critically, and if I feel there is any political agenda, I will catch and disclose it on the social media platforms.

    1. David says:

      And by what objective set of criteria not available to anyone else will you discern whether there is any political agenda? No one has the mind of god.

  65. David says:

    Zinc and polyamines have been examined in cancer studies. Chloroquine is supposedly a zinc chelator, containing a tetramethylenediamine moiety (HCQ not so much).

    But it’s a far cry to extrapolate from a fundamental biochemical or molecular structural knowledge to a treatment of any kind. Yet such fundamentals seem to be the notions that give reason to various adherents of this or that.

  66. Tommy W Hayes says:

    What about the large study that you reported that was retracted ? Do you have a retraction for us?

    1. Coll says:


  67. Sandeep Kapatkar says:

    If not hcq zn, what r the patients and doctors doing in hospital? Death game or money game?

    1. Edward R says:

      My understanding is that it’s $13,000 for a hospitalized covid patient and $39,000 for a covid patient you can get on mechanical ventilation.

      With so many elective surgeries being postponed hospital CFO’s and CEO’s would probably like to see as many of both for as short of a period of time as possible to help cover shortfalls and maximize profit.

      A simple and successful outpatient treatment of HCQ + Az + Zn is their worst possible scenario. Not saying they are even thinking about this issue… just that the current revenue incentives line things up that way.

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