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An old malaria medicine, hydroxychloroquine, has gone viral on the internet. But is it really an antiviral drug?

The medicine has been seen as a potential treatment for Covid-19, the disease caused by the novel coronavirus SARS-CoV-2, almost since outbreaks started. This week it made headlines, due in part to tweets from President Trump and in part because of a small French study of 42 patients that seemed to show that hydroxychloroquine, particularly when combined with the antibiotic azithromycin, helped decrease patients’ levels of coronavirus. Unfortunately, the rumors about the drug’s efficacy have also encouraged some to buy and even consume a similarly named fish tank cleaner; one person has died.

But a second study emerged last week from Shanghai University in China of 30 patients hospitalized for Covid-19. Whether patients received hydroxychloroquine or not, their body temperature returned to normal a day after hospitalization, and the time it took for levels of the virus to become undetectable was comparable. Unlike the study from France, the patients in this study were randomly assigned to either hydroxychloroquine or the control group, which makes the results more reliable.

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Jun Chen, one of the authors of the Shanghai study, called the French study’s results “interesting” but said they needed to be evaluated in another randomized study.

“Both our study and theirs had many limitations,” Chen wrote. “But personally, I would say that hydroxychloroquine was not a ‘magic’ drug, if there is any antiviral effect. And in fact, hydroxychloroquine has never been effective in any viral diseases, despite its in vitro antiviral activity.” “In vitro antiviral activity” means that the drug stops the virus from infecting cells in the dish.

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The first mention of the Shanghai study came from a paper in The Lancet Global Health, where the results were described as positive. One of the authors of the Lancet paper, Oriol Mitjà, wrote via email that changes on CT scans showed “that the drug has some efficacy” against Covid-19. In the Shanghai study, worsening of the disease that could be picked up on a CT scan happened in 33% of those on hydroxychloroquine (that’s 5 patients) versus 47% of those in the control group (7 patients).

Mitjà was even more optimistic about the French study, saying it has “new and stronger data.”

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But objections have been raised to the French study  paper, even as it’s bounced around the Internet. Fox host Sean Hannity even shared another doctor’s letter on his experience using the hydroxychloroquine/azithromycin combination on his television show on March 23.

Three statisticians published a review of the French study that argued that the way it was designed made the treatments look better than they actually are. They pointed to the lack of randomization, as well as an inappropriate control group composed partly of people who refused to take the drug. They also noted that the study dropped some patients from the analysis — the small study of 42 patients actually only included data from 36. The Shanghai study, which showed less impact from the treatments, adds to the questions about the French study, wrote Tim Morris, a statistician at the MRC clinical trials unit at University College, London.

“The [French] study gave very little useful information about whether hydroxychloroquine might help,” Morris wrote. “The Shanghai study is better (because they had a meaningful control group) but gives us very little information that hydroxychloroquine doesn’t help.” The data, he wrote, are “compatible with a wide range of possible effects,” which is statistician-speak for, “Nobody knows whether the drug helps or not.”

The Shanghai study, Morris wrote, is a step in the right direction toward some bigger, better trials that are kicking off. The first of these might give some answers in April — a short time when it comes to clinical trials, but potentially after the United States, and particularly New York City, will have seen a tsunami of Covid-19 cases.

Some doctors on the front lines will use these drug combinations, particularly with patients who are so sick they are on ventilators. As one doctor told me, the risks associated with these drugs, like heart rhythm disturbance or worsening psoriasis, don’t warrant not using them in patients who are in serious trouble. But there is also a need to conduct studies of them to find out if they are truly effective. New York Governor Andrew Cuomo signed an executive order saying that pharmacists should not dispense the drugs to treat Covid-19 unless they are part of a clinical trial. Studies for another drug, remdesivir from Gilead Sciences, are expected to read out in the coming weeks.

Zach Weinberg, one of the co-founders of Flatiron Health, a division of Roche, remembers the difficult transition of going from working in online advertising, where his first company was focused, to Flatiron, which is focused on cancer. In software, more data is better. In cancer, the wrong type of data can lead to conclusions that are not only incorrect but dangerous.

“Sometimes people confuse saying, ‘the study doesn’t tell you anything’ with saying the drug doesn’t work,” Weinberg said. “That’s a really important distinction. They’re not the same thing. I’m not saying the drug doesn’t work or does work. What I’m actually saying is nobody knows if the drug works or doesn’t work.”

His lesson: when dealing with a pandemic, listen to experts who are used to grappling with these problems.

“Society tends to put people who’ve been successful in one area on a pedestal, and draw the conclusion that means they’re expert at many things even though the expertise that they had in one area has nothing to do with the other,” Weinberg said.

  • Matthew, You are missing this paper from China, of 100 patients taking chloroquine. Superior to control. They recommended that it be included in the Chinese Guidelines for prevention and treatment. https://www.ncbi.nlm.nih.gov/pubmed/32074550
    Also, you might be interested in this protocol of a combination of hydroxychloroquine, azithromycin and zinc sulfate. https://docs.google.com/document/d/1SesxgaPnpT6OfCYuaFSwXzDK4cDKMbivoALprcVFj48/edit
    Apprently, the reason chloroquine works so well against most viruses is because it is a zinc ionophore, meaning that it brings zinc inside the cell, which results in the apoptosis.
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4182877/

  • Hate to say it, but hard to trust anything coming from China. We will need to look at our results.

    • I agree with you. I would not trust anything that comes out of China. We should have data form our studies next week.

  • The normal medication rules must flex in this tsunami-style pandemic. What works in one country is worth using in another, certainly if there are no detrimental side effects. Right now the tussle of who said or did what seems so futile. Use what works to address the wild-fire spread and get patients back on their feet. Keep records in your own country. Involve techno’s for analysis. Follow up later. Personally I don’t trust any info from China – many now suffer and die due to their ingoramous attitude in the first 2 months Covid-19 spread there.

  • My Dad was ventilated for 4 days before he got the covid 19 diagnosis. On Tuesday March 24 he started on the hydrochloroquine medicine. On March 26th he was taken off the ventilator with only an optiflow for his breathing. Today, Marxh 27th he called me. Hydrochloroquine worked for my Dad. Thank you West Penn hospital for using this drug. If not for hydrochloroquine and lots of prayers, my Dad would not be here.

  • I think there are at least 4 cases in US where the combo saved folks. Zithromax does show antiviral activity and Hydroxychloroquine method of action is it slows rapid immune response that causes death and it slow virus replication by blocking receptors the virus seeks. While I am not a doctor, I have following closely and believe it will work on many many people.

  • This suggests there are 50Million on-stock doses. Why aren’t they being distributued to pharmacies to meet on label use?

    “When supported for use in COVID-19 infected patients by regulatory authorities, Novartis intends to donate up to 130 million 200mg doses by the end of May, including its current stock of 50 million 200mg doses.

    The Swiss company is also exploring further scaling of capacity to increase supply and will work with manufacturers around the world to meet global demand.

    Sandoz currently only holds a registration for hydroxychloroquine in the USA, and will pursue appropriate regulatory authorizations from the US Food and Drug Administration (FDA) and the European Medicines Agency.”

  • JC- Six patients left the study and recovered, 1 died day 3. To be clear, there’s no evidence that “6 patients got worse.” But there’s plenty of proof on page 24 that all who completed the 6 day regimen recovered markedly faster than the control group. Then there’s the NY doctor that says he treated 350 out 350 patients 100%.

  • This article (and others citing the Shanghai study) fail to mention the HCQ patients were compared to a group that received “conventional Covid19 treatment” which includes lopinavir and ritonavir HIV antivirals which are both very expensive and also of unproven benefit. Regardless, low cost and safe HCQ should be made available to those with first symptoms, test positive and are otherwise healthy. Doctors should not be hording or prescribing it otherwise, or for “just in case”.

  • Is there any reason this article cites the Chinese study as casting doubt on the efficacy of hyroxychloroquine with Azithromycin treating covid-19 when the Chinese study did NOT include azithromycin?!? The French study shows a CLEAR fast recovery in ALL patients- granted sample size is small- and a NY doctor is claiming 100% success with 350 patients AND there is ZERO evidence to the contrary. I just talked to an elderly associate who is mortified of what he’s heard about coronavirus and when I mentioned HCQ/ ZX as a cure, he blasted me and won’t even consider- he sited this same Chinese study and wouldn’t even consider this is being used to dumb down potential covid-19 victims. Most of us totally understand both these drugs are safe, effective, proven, but they’re also cheap due to generics and no current patents. It’s such a shame (what’s left of the) media chooses to propagandize and kill than to educate and eradicate.

    • The French study does not show improvement in all patients. They exclude the six patients who got worse — the definition of “informative censoring”.

      Imagine your teacher dropped your six lowest grades throughout the semester. Would your grade be accurate?

      Especially if your classmates had to include all of their assignments in their grade.

      Could you really say your average was better? No. That’s how the French study did their analysis.

  • It appears, from what I can gleam from different Doctors who are speaking up, that these older drugs have been showing results, just not in a clinical setting. The malaria drug/ z-pak/ ect ect my not be a cure, but the benefit from using these to possibly keep the critical from having to go onto a ventilator, or shortening the duration for the suffering should be looked into with a lot more vigour. To act as a aid in “flattening the curve” to give to the many doctors and health providers when they are infected, the last count I know is that 30 Doctors have died around the world. This is not acceptable if there is a drug that can lessen the duration. I have listed a group of doctors I have found. Thank you Stay kind and brave.
    https://forward.com/news/national/442285/coronavirus-hydroxychloroquine-trump-doctor/

    https://www.youtube.com/user/USMLEOnline

    KudosMD, Dr Oz, Kim Woo-Too Korea University Guro Hospital, Doctor Mike Hansen,
    Dr. William Graze Lenox Hill Oncologist New York

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