The disappointing results of hydroxychloroquine for covid-19 patients

“Study finds no benefit, higher death rate in patients taking hydroxychloroquine for Covid-19” (CNN) is discouraging. We’re apparently not on track to have a better drug treatment for coronavirus infections any time soon, thus potentially casting doubt on the value of “flatten the curve”. If we should be unfortunate enough to get seriously ill from COVID-19, we’ll get the same drugs next month that we would have gotten last month.

(Maybe flattening the curve is still worthwhile because then everyone can get onto a ventilator if necessary? “Nearly all Covid-19 patients put on ventilators in New York’s largest health system died, study finds” (CNN) says that 88 percent of patients on ventilators died. The true number is probably higher, since a lot of patients suffer so much organ damage that they die after being discharged from the hospital where they were on the ventilator. This number is consistent with what my physician friends had told me and what the Chinese found; see April 2 post.)

Should we abandon hope for hydroxychloroquine? A doctor friend responded to my questions with, essentially, “not on the basis of this VA study”:

  • It didn’t fail for indication / mechanism of its action
  • It’s a study done at the wrong stage of disease for the drug to work
  • So much garbage published
  • It works at very early stage of disease to block viral replication
  • If you give it to people who are dying in icu from cytokines storm it’s useless
  • They didn’t separate the patients

(she had only skimmed the paper, so might be wrong about some details)

Not everyone is upset at the failed outcome of this study. My Facebook feed has been alive with glee that the drug does not help people who are suffering and dying from covid-19. They write posts highlighting Donald Trump’s expressed enthusiasm about the drug back in March and then linking to articles about the VA study. Oddly, these expressions of delight come from the same people who are most vocal in their demands for additional shutdown because suffering and dying from covid-19 must be avoided at all costs. This is consistent with my April 7 post:

As much as I want this whole Covid-19 thing to be over, my biggest fear is that it will abate and the stock market/economy will rebound in time for the November election and Trump will claim credit and be re-elected.

Yet I was still unable to think of any situation in which so many people have been happy about a failed drug trial.

Readers who know more about medicine and pharma: Based on the trials that have been done, do we know whether hydroxychloroquine helps covid-19 patients? Anything else that seems promising for the near-term?

Related:

21 thoughts on “The disappointing results of hydroxychloroquine for covid-19 patients

  1. You know what Obama always says!!!!!!!! If you like your hydroxychloroquine you can keep it!

  2. Whatever the merits or lack thereof hydroxycholoroquine, this is all now about the removal of Dr. Rick Bright from BARDA. He was an outspoken critic of using it and is now seeking reinstatement, represented by Debra Katz, who represented Christine Blasey Ford in her testimony against Brett Kavanaugh. So it couldn’t get more political. The #MeToo movement can now line up against hydroxycholoroquine.

    https://www.cnbc.com/2020/04/22/coronavirus-treatment-vaccine-doctor-says-worry-about-trump-idea-led-to-ouster.html

    “Bright also wrote, “Specifically, and contrary to misguided directives, I limited the broad use of chloroquine and hydroxychloroquine, promoted by the administration as a panacea, but which clearly lack scientific merit,” he said.”

    I happen to think that the probability of *ever* developing a vaccine that confers lasting protection (meaning, something like a year or more, similar to an influenza vaccine) to a coronavirus is low. It’s never happened before. I think we’re going to be basically stuck with mitigation strategies and the virus will be around forever.

    It looks like hedge fund interest picked up in Vaxart last year. They popped to $3.15 on 3/21 and yesterday fell $2.95 to $0.21. So their good news didn’t last very long. New data is emerging all the time.

    https://en.wikipedia.org/wiki/Vaxart

    “Vaxart, Inc. is an American biotechnology company focused on the discovery, development, and commercialization of oral recombinant vaccines administered using temperature-stable tablets that can be stored and shipped without refrigeration, eliminating the need for needle injection. Its development programs for oral vaccine delivery (called VAASTTM) include prophylactic, enteric-coated tablet vaccines for inhibiting norovirus, seasonal influenza, respiratory syncytial virus, and human papillomavirus. In 2019–20, Vaxart began a program to develop an oral tablet vaccine for the 2019 coronavirus, COVID-19.[1][2][3]”

    Maybe Trump should have cited David Hockney and told people to start smoking.

    https://www.dailymail.co.uk/health/article-8246939/French-researchers-plan-nicotine-patches-coronavirus-patients-frontline-workers.html

    Was Hockney RIGHT? French researchers to give nicotine patches to coronavirus patients and frontline workers after lower rates of infection were found among smokers

    “A French study found that only 4.4% of 350 coronavirus patients hospitalized were regular smokers and 5.3% of 130 homebound patients smoked. This pales in comparison with at least 25% of the French population that smokes.”

    • > the probability of *ever* developing a vaccine that confers lasting protection … is low.

      Agreed but I suspect there is a much higher probability of developing a not-too-harmful vaccine that confers lasting and enormous profits for the pharmaceutical industry and their political backers.

    • @Lord Palmerston: In fact, the message from big pharma is that billions of dollars in “financial commitments” will be needed to underwrite the continuing effort to develop and produce vaccines, before they’re even shown to work. Kind of a “pre-bailout” bailout. The top 20 pharma companies lost 2.6 trillion in market capitalization in Q1, and they want not just a guaranteed market, they want their development costs funded:

      Hey, they’re not alone. Everybody wants the government to bail them out for as long as it takes, whatever it takes, including the governments of all our states and municipalities. That’s not going to happen either, but there will be winners and losers, just on a grander scale than we’ve ever seen in history.

      https://www.biospace.com/article/top-20-biopharma-companies-lose-2-6-trillion-market-cap-in-q1/

      “David Loew, executive vice president of Sanofi Pasteur, one of the top vaccine manufacturers in the world, indicated governments would *** need financial commitments in the billions to underwrite the acquisition of the most promising vaccines even before proof they were viable. ***
      “If the industry does not know if there will be a market in 18 months, [it] cannot carry all [the costs],” he told the Financial Times. “Industry alone can’t provide all the investment needed now for billions of doses.”

      At least some of the concern is that without greater funding and coordination, the companies won’t be able to buy sufficient raw materials, continue production of existing drugs and quickly scale up their capacity to meet the demand of new drugs and older therapies around the world.”

      There’s not enough money in the world…

  3. @Toucan Sam: If you’re interested, STAT is hosting a Zoom webinar on the coronavirus with Dr. Rich Besser, former Acting Director of the CDC under the Obama administration, now president and CEO of the Robert Wood Johnson Foundation, next monday at 11 a.m. EDT. Philg’s Facebook friends should love it.

    “He has drawn on his experience to offer both criticism and commendation of global response efforts to the pandemic, and has emphasized the health inequities being brought to light as a result.”

    https://www.eventbrite.com/e/stat-video-chat-a-conversation-on-the-coronavirus-with-rich-besser-tickets-102892209368

  4. For those who are interested in the details, the news articles Philip cites are based on these original articles,:
    Outcomes of hydroxychloroquine usage in United States veterans hospitalized with Covid-19
    https://www.medrxiv.org/content/10.1101/2020.04.16.20065920v1

    Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients Hospitalized With COVID-19 in the New York City Area
    https://jamanetwork.com/journals/jama/fullarticle/2765184

    The figures in this table from the second paper are especially grim:
    eTable 1. Clinical Measures and Outcomes for Patients Discharged Alive or Dead at Study End Point – By Comorbidity

  5. It’s a gigantic muddle. Where’s the Holtgrave study? As of yesterday morning, it’s in the infinite elsewhere.

    https://www.cnn.com/2020/04/22/health/hydroxychloroquine-new-york-study-results-unreleased/index.html

    “New York researcher says preliminary results of hydroxychloroquine study are ready, but state hasn’t released them”

    On April 12, New York Gov. Andrew Cuomo said, “about April 20 we think we’re going to have results.”

    When results were not announced on Monday, CNN asked why not. Cuomo answered that the hospitals “are to send their results” to the US Food and Drug Administration and the US Centers for Disease Control and Prevention.

    The CDC has not received results from the New York hospitals, according to agency spokeswoman Kristen Nordlund.

    CNN did not receive an immediate answer from a spokesman for the FDA.

    The New York Department of Health did not respond to CNN’s inquiries about when it plans to release the study results.

    Tuesday, after Cuomo met with Trump at the White House, a reporter asked Cuomo if he had “any indication of what the state results have been.” Cuomo answered that he did not know.

    Holtgrave, dean of the University at Albany School of Public Health, said he plans to finish his study analysis by the middle of next week, and publicly release it within a few days.

    “We’re continuing our work every day on this study and anticipate having our final analysis in place by the end of April,” he said, adding that “it’s very important get final results study out quickly as possible” so that doctors and patients can make decisions about whether to use hydroxychloroquine.

    #MeToo !

  6. Is your theory more or less that the Novel Coronavirus (and its various strains) will end up more or less like pre-vaccine chicken pox, floating around the population, relatively harmless in childhood, potentially awful or lethal in adulthood, but more or less inevitable on an individual level? And further, if that’s the case, then lockdown/flattening is really just slightly delaying the inevitable for the individuals concerned. (If that’s the case, then the moment it became pandemic, a lot of people became dead men walking!)
    It seems that you’re saying that, without a way to improve the eventual outcomes, we might as well just bite the bullet and let the bulk of the population contract it, because, at least that way, our economy could become productive again.
    I think this is a bitter pill to swallow for a lot of people that hold out hope that drugs, a vaccine, or intensive care could improve outcomes if available to vulnerable sufferers, especially given the enormous sunk costs at this point (A few trillion dollars of inflation money printed, huge disruptions to everything for a couple of months). The most concerned in my facebook feed say we’re looking at another 18 months of distancing (interestingly, they also seem to see this as a model for how we could tackle global warming) Which politicians are going to be willing to lead the “it’s better that grandpas die now in a healthier economy than in 17 months in a wrecked one” charge? American politicians are not know for being good at delivering bad news.

    • SuperMike: I wouldn’t say that whatever I think is MY theory since I’m not an epidemiologist. Of the information that’s been put out by experts, I think the Swedes make the most sense. A primary point, as I understand them, is that Western governments simply do not have the power to substantially change the number of infections and deaths (assuming a basic level of competence within a health care system to handle a flu-like surge in patients). A conclusion based on this point is that the difference in viral spread between a Swedish-style “hey, stop gathering in huge crowds, but keep going to school, restaurants, and offices” policy and an American-style non-lockdown lockdown is minimal.

      A secondary point from the Swedes is that the coronavirus, possibly in a mutant form, will always be with us (as Jesus said about the poor! Look how rich people in the Bay Area who say that their first priority is social justice have learned to drive by the homeless encampments in their new Teslas!) and therefore we have to learn to live with it. Also, that progress in vaccines and medicine is so slow that we can’t stay in our bunkers until there is a big improvement in these areas. I agree with this point too.

      The idea from particular Swedes that the ultimate death toll from coronavirus will be similar to that from a bad flu season is one that I have less confidence in. Everyone is forced to guess about this right now, especially if the virus is mutating. But, whether the ultimate death toll is more or less than it would be from a severe flu, the rest of the Swedish plan remains valid. You can impoverish yourself and the rest of the world on your way to X% deaths. You can keep educating children, working productively, and socializing with friends and family on your way to X% deaths. A belief that X is a high number is not a reason to try to stay in an ineffective Western-style lockdown since it won’t change X.

    • LinePilot: A moderately bad flu season in the U.S. can kill 80,000 people (and about 650,000 people worldwide, says WHO). https://www.statnews.com/2018/09/26/cdc-us-flu-deaths-winter/ That’s 242 per million (I think it is on your chart as the yellow 2017-18 curve, 10-20 deaths per million per week over 33 weeks).

      Sweden hasn’t run out of ICU capacity for COVID-19 patients (partly due to some hasty prep work), but they ran out of hospital beds in 2016 due to ordinary influenza: https://www.thelocal.se/20161229/winter-flu-puts-karolinska-in-crisis-mode (the article refers to a 2009 crunch due to swine flu).

      COVID-19 is “flu-like” in that there is no cure from medicine and the treatment with oxygen and, as a last resort, ventilators, is similar. Flu and COVID-19 are also similar in that you need to stockpile PPE to prepare for an outbreak of either.

      I think COVID-19 might be so similar to flu, actually, that it is largely medically irrelevant whether a patient has COVID-19, SARS, MERS, or influenza. https://en.wikipedia.org/wiki/Li_Wenliang on December 30 identified the Wuhan outbreak as SARS, for example. With any of these, however, I think the hospital staff does the same thing: put on a mask so as not to become infected oneself, then support the patient’s breathing and hope that his/her/zer/their immune system kills the virus.

      As of today, the WHO shows 40,000 COVID-19 deaths in the U.S. (Situation Report 94). A week ago (Report 87), it was 18,579. So that’s 65 deaths/million in the last week, which the prophets of U. Washington say was our peak. https://covid19.healthdata.org/united-states-of-america

      The chart you’ve linked to makes it look like COVID-19 is an exponential disaster that is unprecedented and that cannot be comprehended. But if they’d extended it out another week it would show the beginnings of a Bell Curve shape and the top would be less than heart disease and cancer combined. COVID-19 would have a much tighter curve than the 2017-18 flu season with a similar area underneath. That’s “flu-like” I think, even if it isn’t exactly the same as the 2017-18 influenza wave.

  7. NY doctor has treated 1450 covid patients, those with high-risk given 3-drug combo of HCQ + Zinc + azithromycin. Results: only 2 dead, 4 respirators; NY hospitals have 10x higher rates. He claims Zinc is the key that stops virus replication, but it needs the HCQ as a “pathway” to enter cells; azithromycin is an antibiotic to treat secondary infections. Claims HCQ on its own is ineffective.

    Interview w Dr Z: https://www.youtube.com/watch?v=-K7lnW9_xnw

    • You then need another doctor that was treating about the same number of patients, similar ages, health conditions, similar occupations, living in the same geographical area, admitted at a similar stage in the disease, and give them a placebo. Only then would you know if the 3-drug combo was effective.

      Science is hard.

      No wonder all the miracle cures and treatments always come from youtube or dubious websites, and not in peer-reviewed scientific articles? And all the cranks associated with them are often conservative or right-leaning? Well, it is just like climate change, but in an accelerated way (as you can disprove the bullshit much faster).

    • @Philg: Funny you should mention that. I posted a longer reply that went to moderation, but the gist of it was that anyone with three pieces of information who knows how to speak the mumbojumbo can get a study on COVID-19 listed on an NIH website. Like this one:

      Determination of the Effectiveness of Oral Chlorine Dioxide in the Treatment of COVID 19

      https://clinicaltrials.gov/ct2/show/NCT04343742

      The “Responsible Party” is one Dr. Eduardo Insignares Carrione, originally from Bogota, Colombia.

      https://ieaninepoints.com/2007/08/02/2007-correlation-between-psychotypes-and-biotypes/#myaccount

      Wouldn’t it be hilarious if someone is feeding links to junk-science studies on an NIH website to the President to make him look like an idiot?

  8. Vanity Fair just released an article on the Trump administration’s push for hydroxychloroquine. “Really Want to Flood NY and NJ”: Internal Documents Reveal Team Trump’s Chloroquine Master Plan.

    WH call. Really want to flood NY and NJ with treatment courses. Hospitals have it. Sick outpatients don’t. And can’t get. So go through distribution channels as we discussed. If we have 29 million perhaps send a few million ASAP? WH wants follow up in AM.

    We can get a lot more of this. Right Bob? Millions per week?

    Apparently Trump talked about injecting disinfectants at today’s daily briefing.

    Summary of investigation into therapies, from the BC CDC:

    There are currently no approved therapies for COVID-19, and no therapies have been robustly evaluated. The majority of published evidence that have suggested treatments for COVID-19 is extrapolated from experience with SARS, MERS or limited to case-series. Randomized-controlled trials are ongoing, most notably with three agents: 1. lopinavir/ritonavir (Kaletra), an anti-retroviral used for treatment of HIV; 2. remdesivir, a novel investigational antiviral; and 3. hydroxychloroquine, anantimalarial drug with antiviral activity ​in-vitro​. Other agents also under investigation including immunomodulatory agents used to attenuate COVID-19-associated cytokine storm such as tocilizumaband sarilumab. As of April 10, 2020, the Cochrane COVID-19 Study Register lists 490 interventional studies of which 285 are randomised trials.

    • If it doesn’t work as well as a placebo then it can be marketed as a miracle cure for a psychiatric disorder.

  9. > the biggest sources of fake miracle cures are government-funded academic scientists and pharma companies!

    Funny you should mention that. Wanna see something screwy about the “disinfectant” thing? There actually is a “study” listed on ClinicalTrials.gov, run by the U.S. National Library of Medicine through the NIH, describing the following:

    Determination of the Effectiveness of Oral Chlorine Dioxide in the Treatment of COVID 19
    https://clinicaltrials.gov/ct2/show/NCT04343742

    Abstract The objective of this study is to review, through prospective case research, the efficacy of oral chlorine dioxide in the treatment of patients with COVID infection 19. The research will be carried out between April and June 2020 with a quasi-experimental design in two health care centers on a sample of twenty (20) patients, through direct intervention, who will measure the changes in the manifest symptoms of infection and negativity. a COVID 19 after administration of the study preparation, to determine the effectiveness of chlorine dioxide in the treated group.

    The “Responsible Party” for getting this study listed in the government database is one Eduardo Insignares Carrione, Genesis Foundation. His address is listed as 7747 SW 86th St. Miami FL. Other bio. data indicates he’s from Bogota, Colombia and received the Colombian National Award of Medicine.

    His name comes up in connection with the Eneagram, Orthomolecular therapy (whatever that is), some company called Nutricell, U.S.A. out of Florida, a whole bunch of quack stuff.

    How does one get a study listed in the NIH-run U.S. National Library of Medicine? Here:

    https://clinicaltrials.gov/ct2/manage-recs/how-apply

    There are all sorts of things to read. In the end, though, apparently all you need to log in to PRS is to type the day of the week and then supply an organization, a username and password.

    https://clinicaltrials.gov/ct2/manage-recs/register

    So it looks like basically any whackjob who has access to preexisting PRS (Protocol Registration and Results System) credentials can log into the system and register a study on the effect of the number of furlongs per fortnight on the dispersal of COVID-19. And any idiot can then supply a link that could lead an elected official to a U.S. Government website showing that a study is being conducted. The gullible elected official might even be the President of the United States.

    Here’s the FAQ: https://clinicaltrials.gov/ct2/manage-recs/faq#find
    Can an organization have multiple users for a single account?

    Yes. When sponsors or their representatives register to become PRS data providers, they will be given information on using PRS, including instructions for creating additional user accounts. See How to Apply for an Account for more information.

    Here’s some more information about Dr. Eduardo Insignares-Carrione:
    https://ieaninepoints.com/2007/08/02/2007-correlation-between-psychotypes-and-biotypes/#myaccount

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