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.

  • Doctors are writing themselves RXs for Plaquenil – ‘just in case.’

    Meanwhile, patients that need this medicine on a daily basis can’t get it. There are millions of people that may end up in the hospital because of symptoms and complications from stopping this medicine.

    Do we need the ERs flooded with millions of patients right now? No!

    The doctors who are unethically writing RXs for Plaquenil and the Druggists who fill them should all go to jail. We need a congressional hearing on this and expose the culprits.

  • Hydroxychlorquine is generic, meaning no one will make any money if this treatment works. Gilead’s remdesivir will be proprietary, meaning they will make billions. Today, under social pressure to do so, Gilead requested a removal of orphan status for remdesivir which would have given them extended commercial patent protection. Gilead’s history can be summed up here: “Gilead priced its first new hepatitis C drug, sofosbuvir, at $1,000 per pill, or $84,000 for a three-month course of treatment. Its first combination pill, Harvoni, cost $94,500.May 7, 2018”

    Who do you think may be influencing how this story unfolds?

    • Of course , if Hydroxychlorquine works well, there will be less sales for the very expensive drugs. So there is a lot of money in discrediting Hydroxychlorquine research.

  • Statistical significance of this test is 10,000**. The FDA has accept results 1 to 20. Is having a cure so hateful to everyone’s ideas? They you are dangerous.

    **Dr. William Grace, NYC

  • We absolutely know that it works!
    “Dr. Vladimir Zelenko thanked the President for securing approval for the use of hydroxycholorquinine with Azithromycin. The doctor is a general practitioner in a Hasidic community, which is hit hard by Coronavirus — about 60 percent have the illness. He has had a 100 percent success rate with the drugs, using it on 350 patients.”

  • The FDA needs to eliminate proving efficacy as a precondition of drug approval. People need to make decisions based on their own judgement and risk standards. People have a right to take drugs without the intellectual certainty of a scientist and without the permission of a bureaucrat.

    • I’m sorry, but have you met people?

      You seriously believe that your Auntie Em can make a well-informed decision about the utility of, say, losaratan vs betaxolol, especially a) in an emergency situation and b) in a situation in which there isn’t comparable efficacy data?

      This isn’t an area where sledgehammer approaches improve anything. Find something you can fix with a scalpel instead.

  • Matthew, the discussion in the French study exhibiting the positive effect of hydroxychloroquine combined with azithromycin in comparison to hydroxychloroqine alone is not mentioned in your otherwise factual article. The Shanghai study did not study the combo.

  • Plaquenil. Per review of literature may help control the protozoan related to uncomplicated malaria. No proof exists that hydroxychloroquine (plaquenil) is effective against a corona virus. The anti-inflammatory and immune modulation effect reduces the damage caused by Lupus, Rheumatoid arthritis and other autoimmune diseases. This medication may reduce a normal person’s immunity allowing them LESS resistance to corona virus, by reducing the body’s natural immune protection. Hydroxychloroquine may reduce damage to lungs caused by corona virus. The current hysteria has made obtaining hydroxychloroquine near impossible thus causing severe harm and possible death to the segment of population suffering from Lupus. The government needs to inform their citizens with the real facts. Please be responsible, my darling wife needs this medication – she only has 20% use of her kidneys from autoimmune nephritis.

    • The drugs discussed are already being prescribed for everyone who is getting killed by the virus BECAUSE OF COVID REACTIONS ON THE IMMUNE SYSTEM.
      Older people actually have proven to have well developed immune system but in the case of some viruses like the one we are dealing with presently all over the Earth, the “storm of immune resistance is actually killing the patience.
      So, the treatments have split into two different approaches to two different groups. Those who are going to die if they are made to take on the virus directly are given Hydroxychloroquine/Azithromycin. Dr. William Grace, NYC and other Doctors are already currently providing these treatments. The FDA can do testing on those not on the verge of dying from this VIRUS ATTACK IMMUNE SYSTEM REATIONS. SEE?

    • It tends to take hydroxychloroquine a month or two to be effective against autoimmune disorders. I read that it can sometimes take up to six months once a person starts using it. I think it remains in the system for about 40 days after a person stops using it. I don’t know if that applies to long-term use or both long-term and short-term use. However, it seems that short-term use to treat coronavirus should not adversely affect the average person’s immunity.

      My local pharmacy is only filling seven days’ worth of the drug for customers who do not have autoimmune disorders. I wonder if other pharmacies are doing full 30 day fills or if they’re also limiting the amount. Manufacturers are said to be stepping up production. Hopefully, additional stock will be available soon.

    • @Mick you can’t get any amount of this drug where I live. You can’t get it from mail-order either. It doesn’t matter what amount they’re informed to provide. The doctors and dentists all prescribed tons of it to themselves and their friends just in case and left millions of us without it. If it takes 6 months to help a patient, that’s worse. Not only does one have to wait out the pandemic and hope to survive, but wait another six months more to feel well again and survive that six months as well? That’s huge. I take this medicine and like millions of others will have to go to the ER because of the run on this medicine which will easily quadruple the pains on the healthcare workers. People need to lose their license to practice and go to jail.

  • It may. It may not. There are better alternatives out there.
    Favilavir, aka Avigan, is a Japanese antiviral approved for use against COVID-19 in China and Italy (only drugs approved for this disease)…no idea why others are not rushing to this drug. Only real reason is Political Hype. Trust the people who are/were desperate….and follow their approvals.

    • Hydroxychloroquine/Azithromycin is only the second cure for any Virus disease in History. Apparently the word CURE is too strong of a word for comprehension. Worlds like controlled random testing, approval, vaccine development, etc. is more important to the mind than CURE?

  • I find an issue with the Shanghai study. From the following article:
    https://www.fiercepharma.com/pharma-asia/did-chloroquine-really-fail-a-covid-19-study-or-was-it-just-trial-design-s-fault

    ‘However, most patients in the study’s control group were actually treated with other antiviral therapies at the same time, including AbbVie’s HIV combo med Kaletra and flu drug Arbidol. Most, but not all, patients in the hydroxychloroquine group were also treated with Arbidol. All patients got interferon-alpha.’

    So if the solid majority of patients was receiving other anti-viral treatments, how can we measure the effectiveness of hydroxychloroquine?

    • It’s almost as if the the study was conducted to mislead. Hard to believe news out of China would be misleading.

  • “……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. ……..”

    I can’t understand this position. If a drug is known to be adequately safe in prescribed doses, but its benefit is unknown, then I can see no harm in prescribing it, in the clear knowledge that it may not assist, but is unlikely to harm.

    Chloroquine is also believed to have a prophylactic effect. Again, we have no firm data. But given the requirement for such protection for front-line medical staff, it would seem to be justifiable to make Chloroquine doses available for them. Time is of the essence, and pre-loading their bodies would be valuable if a trial provides positive evidence that the drug is of value.

    • “Chloroquine is also believed to have a prophylactic effect.” Have we tested a randomized sample of say 10,000 lupus patients on Chloroquine to see if any have contracted Coronavirus? That might tell us something.

    • @Andrew M, we can’t test lupus and other patients that already take Plaquenil because they can no longer take it.

      Everything is going to be much worse. The ERs are going to be flooded with patients that would be home resting but are having a sudden acute health event because of some bozo doctor and their cohorts hoarding all the medication.

      People need to lose their medical licenses and go to jail. Period. I don’t want doctors that unethical treating any of my loved ones.

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