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Hydroxylchloroquine wars, 4: Didier Raoult strikes again, with 80-patient test

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BREAKING: Professor Raoult has released a further result. Using Google Translate on two tweets:

Our two articles published this evening help to demonstrate:

     1. The effectiveness of our protocol, on 80 patients.

     2. The relevance of the association of hydroxychloroquine and azithromycin, thanks to research carried out in our P3 containment laboratory. https://t.co/Y91bsFOgB2

     – Didier Raoult (@raoult_didier) March 27, 2020

and:

New article published online by my teams: in vitro demonstration of the hydroxychloroquine / azithromycin synergy to counter the replication of SARS-COV2

     In vitro testing of Hydroxychloroquine and Azithromycin on SARS-CoV-2 shows synergistic effecthttps: //t.co/KUaag6N5FF

     – Didier Raoult (@raoult_didier) March 27, 2020

Here is a chart in one of the Twitter threads, which seems to document the efficacy of the HCQ-Z-pac cocktail across 5 – 6 days of treatment:

Of course, there is also a suggestion on Zinc supplements.

Let’s see how this further develops, one way or the other. END

U/D1: After searching, I found at Professor Raoult’s Institute as follows.

Exhibit 1, on the 80 patient study:

Clinical and microbiological effect of a combination of hydroxychloroquine and azithromycin in 80 COVID-19 patients with at least a six-day follow up: an observational study
Running title: Hydroxychloroquine-Azithromycin and COVID-19

Abstract
We need an effective treatment to cure COVID-19 patients and to decrease the virus carriage duration. In 80 in-patients receiving a combination of hydroxychloroquine and azithromycin we noted a clinical improvement in all but one 86 year-old patient who died, and one 74 year- old patient still in intensive care unit. A rapid fall of nasopharyngeal viral load tested by qPCR was noted, with 83% negative at Day7, and 93% at Day8. Virus cultures from patient respiratory samples were negative in 97.5% patients at Day5. This allowed patients to rapidly de discharge from highly contagious wards with a mean length of stay of five days. We believe other teams should urgently evaluate this cost-effective therapeutic strategy, to both avoid the spread of the disease and treat patients as soon as possible before severe respiratory
irreversible complications take hold.

Exhibit 2, on an in vitro study showing synergism between HCQ and Z-Pac at concentrations relevant to lung tissues:

In vitro testing of Hydroxychloroquine and Azithromycin on SARS-CoV-2 shows synergistic effect

Abstract
Human coronaviruses SARS-CoV-2 appeared at the end of 2019 and led to a pandemic with high morbidity and mortality. As there are currently no effective drugs targeting this virus, drug repurposing represents a short-term strategy to treat millions of infected patients at low costs. Hydroxychloroquine showed an antiviral effect in vitro. In vivo it also showed efficacy, especially when combined with azithromycin in a preliminary clinical trial. Here we demonstrate that the combination of hydroxychloroquine and azithromycin has a synergistic effect in vitro on SARS-CoV-2 at concentrations compatible with that obtained in human lung.

We thus find a more comprehensive study of patients, and further in vitro results showing synergistic action. Promising, to be further followed up.

37 Replies to “Hydroxylchloroquine wars, 4: Didier Raoult strikes again, with 80-patient test

  1. 1
    kairosfocus says:

    Hydrochloroquine wars, 4: Didier Raoult strikes again, with 80-patient test

    (Where are the two new papers?)

  2. 2
    kairosfocus says:

    U/D 1: I found two papers at the site for the Institute, adding to OP from Abstracts momentarily. KF

  3. 3
    JVL says:

    A nationwide shortage of two drugs touted as possible treatments for the coronavirus is being driven in part by doctors inappropriately prescribing the medicines for family, friends, and themselves, according to pharmacists and state regulators.

    It’s making it hard for people who need those drugs to get them.

    https://arstechnica.com/science/2020/03/doctors-hoard-unproven-covid-19-meds-by-writing-prescriptions-for-selves-families/

  4. 4
    kairosfocus says:

    JVL, hoarding behaviour is unfortunately common, and needs to be countered through confidence in ready supply; the same has been happening with masks etc. That should not be too hard with a generic. However, an implication of such hoarding is precisely that many physicians — a highly relevant group for evaluating evidence — clearly are inclined to believe this may well work. In that context, emphasising “unproven” rather than “promising” speaks volumes on unbalanced partyline media reporting. The OP is showing that further evidence heightening warrant is emerging day by day. It is clear from in vitro studies over 15 years that this drug has antiviral properties, and in concentrations relevant to in-tissue contexts. Not only a significant number of cases but now repeated studies are showing the same. Two from Raoult, an Australian study, a 100 patient study in China come to mind. KF

    PS: These exchanges are also speaking to much broader issues of warrant and how we respond to evidence.

  5. 5
    JVL says:

    Kairosfocus: hoarding behaviour is unfortunately common, and needs to be countered through confidence in ready supply; the same has been happening with masks etc.

    Yes but in this case it’s particularly sad when people who depend on them can’t get them. I did not use the term “unproven” and I can’t change the link.; I will gladly support the use of the drugs in question if the results of the ongoing clinical trials are positive.

    These exchanges are also speaking to much broader issues of warrant and how we respond to evidence.

    That is part of the core gap between ID and unguided evolutionary theory.

  6. 6
    kairosfocus says:

    JVL, the point first is, hoarding is a common problem, relieved by renewed confidence in ready supply. Unfortunately, it means that various types of patients face difficulties for the moment. In that context, I pointed to the terms used by ars technica which are only too reflective of the imbalances and polarised (often politicised) selective hyperskepticism that are afoot. We need to recognise this fallacy for what it is as we disbelieve what we should not because on a related matter we believe what we should not. If your yardstick is crooked, what is genuinely straight and upright will never fit with crookedness. We need to find naturally straight and upright plumb lines and respect their verdict. KF

    PS: In this case, we need to recognise that different degrees of warrant are relevant to different circumstances, depending on what is at stake. Here, there is a difference between warrant sufficient to justify early, experimental or emergency use given stark alternatives and warrant sufficient to justify general, routine use. What we have in hand clearly meets the first level. The second seems to be coming. Note here, the results in the OP.

  7. 7
    ET says:

    JVL:

    That is part of the core gap between ID and unguided evolutionary theory.

    The core gap is that ID has the evidence and the science whereas unguided evolution has the liars and bluffers.

  8. 8
    ET says:

    The WORLD is the clinical trial for the new treatments. And the new treatment has been working. To ignore that is to be willfully ignorant

  9. 9
    Ed George says:

    KF

    PS: These exchanges are also speaking to much broader issues of warrant and how we respond to evidence.

    Nobody is suggesting that this combination shouldn’t be used. If a patient in hospital tests positive I have no problem with having it administered on a routine basis. But until a comprehensive clinical trial has demonstrated its efficacy and, more importantly, its contraindications, it would be irresponsible to prescribe it to people with mild symptoms, even if they test positive.

    Trump, with his poorly thought out pronouncements do more harm than good.

  10. 10
    Truthfreedom says:

    @9 Ed George

    Trump, with his poorly thought out pronouncements do more harm than good.

    So right reason is something valuable. Almost an objective good.
    If not, who are you to judge Trump’s pronouncements? Based on what exactly?

  11. 11
    kairosfocus says:

    EG, who has been advocating broadcast use? (Apart from somebody deciding to swallow aquarium cleaner not for human consumption.) Nearest I see is that prophylaxis would go to critical health workers and maybe to those with danger-sign preconditions. KF

  12. 12
    kairosfocus says:

    EG, TF is right to highlight how in your own arguments, yet again, you appeal to the inescapable first duties and principles of responsible reason. That repeated pattern is trying to tell you something. KF

  13. 13
    ET says:

    Acartia Eddie proves he is ignorant. President Trump said exactly what this treatment is for and when it should be used. And the world today is an has been, the clinical trial, duh. And in the real world the treatment has been working. That is why the President has said what he did.

  14. 14
    Ed George says:

    KF

    EG, TF is right to highlight how in your own arguments, yet again, you appeal to the inescapable first duties and principles of responsible reason. That repeated pattern is trying to tell you something. KF

    Yes, it is telling me that if I want to survive and thrive in a stable society that I have to make decisions that benefit society. Any ‘duty’ implied by this is one that I have established for myself.

  15. 15
    Truthfreedom says:

    @14 Ed George

    … in a stable society

    As if order and stability were good things we all should aspire to. Almost objective goods.

  16. 16
    JVL says:

    Truthfreedom: As if order and stability were good things we all should aspire to. Almost objective goods.

    That’s what works for the majority of individuals so they’re likely to support it, vote for it, strive for it.

  17. 17
    kairosfocus says:

    EG [attn JVL], do you see the appeals to truth, prudence, right reason, fairness and justice etc in your arguments? That’s what I have been pointing out regarding how inescapable first duties and principles of responsible reason are. This points to them being undeniably, self-evidently and so objectively true; indeed, they are the framework on which warrant, including scientific warrant, is built. KF

  18. 18
    JVL says:

    Kairosfocus: EG [attn JVL], do you see the appeals to truth, prudence, right reason, fairness and justice etc in your arguments?

    Yup, I do!

    That’s what I have been pointing out regarding how inescapable first duties and principles of responsible reason are.

    Yup, that’s why I keep referring to the greatest benefit for the greatest majority. We have to look out for other people.

    This points to them being undeniably, self-evidently and so objectively true; indeed, they are the framework on which warrant, including scientific warrant, is built.

    Well, scientific ‘warrant’ is based on repeatable, observer independent truth yes? Stuff you can check yourself. We can all get behind that, and it sounds pretty self-evidently true and objective to me. Perhaps we actually agree on the basic stuff.

  19. 19
    daveS says:

    KF, et al,

    Delurking to say, stay safe & healthy! I hope you haven’t been severely impacted by the pandemic. I’m fortunate to live in the middle of nowhere, with essentially 0 cases nearby, but have close family in some of the hotspots. Everyone’s ok so far though.

  20. 20
    Ed George says:

    Ontario has prohibited doctors prescribing chloroquine for COVID-19.

    https://apple.news/Ag2W32KvaS6Cg796OX9f-3w

  21. 21
    ET says:

    Ontario wants to decrease its population.

  22. 22
    ET says:

    JVL:

    Well, scientific ‘warrant’ is based on repeatable, observer independent truth yes?

    Not according to evolutionism.

  23. 23
    kairosfocus says:

    Hi DS, we just went into 24 hour curfew here, with 5 officially recognised cases. Trust you and yours fare well. Looks like this one is going to hurt. KF

  24. 24
    kairosfocus says:

    JVL, scientific reasoning depends on our being rational, responsible, significantly free thinkers. Indeed, in large measure, it is applied inductive logic. And again, you appeal to first principles and duties of reason, to truth [you think I overlooked a fact], to right reason [fact + logic], etc. Those first principles and duties are inescapably the case, i.e. they accurately describe reality and are true. KF

  25. 25
    daveS says:

    KF,

    Glad to hear you are taking stringent measures. I’m also afraid that we are going to incur heavy losses.

  26. 26
    Jammer says:

    The left is so mad at this treatment. They thought they finally got Drumpf, and the White House was soon to be theirs again. Instead, thousands of lives will be saved, and Trump will ride another four years.

    A double L for our friends on the left.

  27. 27
    Seversky says:

    If chloroquine and azithromycin are effective against COVID-19 then great, let’s get them into full production as soon as possible. But it will take more than the word of a reality-show President who thinks the USAF has Romulan cloaking-devices to convince me. That will need to be confirmed by results from the large-scale trials that are being prepared now.

  28. 28
    ET says:

    seversky, grow up. The President said what he did because the treatments have been used and have worked. He didn’t make it you, you troll.

    That said, Boston hospitals are running clinical trials using remdesivir.

  29. 29
  30. 30
    Truthfreedom says:

    Didier Raoult is the most cited microbiologist in Europe according to ISI and was cited more the 5000 times in 2012. He has trained more than 457 foreign scientists in his lab since 1998 with more than 1950 articles referred in ISI or Pubmed. He is the more prolific French scientist, anytime, in any field.

    And he is a rabid (pun intended) anti-Darwinian. He says that darwinian evolution is p**p.
    https://www.thethirdwayofevolution.com/people/view/didier-raoult

  31. 31
    kairosfocus says:

    Sev, I suggest you read the OP to this thread on recent further results from France, which add to earlier results. I also point to the trend graphs and my discussion of significance, esp. for Bahrain, which began Hydrochloroquine treatment on Feb 26. Fair comment, the reality show President belittling rhetoric is seriously misinformed. There is significant reason to take this seriously, though the talking points and partyline of the bulk of international and esp US media would not lead you to think so. KF

    PS: I further clip from the linked, Bahrain data:

    Total Cases: 499
    of which 1 in severe condition
    Deaths: 4
    Deaths/ Total Cases: (1%)
    Recovered: 272
    Recovered/ Total Cases: (55%)

    Remember, on evidence in hand, they began treatment with hydrochloroquine on Feb 26. Notice from the graphs in the OP for the linked, Bahrain is getting the trend line on fresh cases to begin to flatten.

  32. 32
    Truthfreedom says:

    He is the author and co-author of more than 2000 scientific publications. Didier Raoult is devoted to research in infectious diseases, especially in the field of emerging microbes. His team isolated for the first time over 20% of bacteria isolated in humans, more than 50% of archaes from man, and his team is the origin of the discovery of four viral families, the first virus giant Mimivirus, and also Marseillevirus, Faustovirus the virophage, the first virus infecting viruses by making them sick.

    And he says darwinian evolution is p**p.
    https://www.thethirdwayofevolution.com/people/view/didier-raoult

  33. 33
  34. 34
    kairosfocus says:

    Seversky et al, you would be well advised to click, view and read. KF

  35. 35
    Truthfreedom says:

    When Didier Raoult wrote his articles against darwinian evolution, he says he received a religious reply from certain evolutive people. Not scientific, religious. Can you believe it? 🙂

  36. 36
    Seversky says:

    Kairosfocus @ 31

    Sev, I suggest you read the OP to this thread on recent further results from France, which add to earlier results. I also point to the trend graphs and my discussion of significance, esp. for Bahrain, which began Hydrochloroquine treatment on Feb 26.

    Fair enough, but I would also draw your attention to this article from Science reviewing the controversy surrounding the use of chloroquine:

    When President Donald Trump recently touted the common malaria treatments hydroxychloroquine and chloroquine as potential remedies for coronavirus disease 2019 (COVID-19), he ignited unprecedented demand for the drugs—and set scientists’ teeth on edge. Although the World Health Organization (WHO) agrees the compounds are worth testing more fully on the pandemic coronavirus, few drug or infectious disease experts—not even the president’s own advisers—share his optimism that the drugs could become “one of the biggest game changers in the history of medicine,” as he tweeted. And many are critical of the small French clinical study of just 42 patients that seems to have touched off most of the excitement.

    “The president was talking about hope,” Anthony Fauci, director of National Institute of Allergy and Infectious Diseases, said diplomatically at one of the White House briefings where Trump praised the drugs’ potential.

    Others are less diplomatic. Darren Dahly, a co-author of one of several critiques of the initial study and a principal statistician at the University College Cork School of Public Health, said it would be “egregious” to recommend treatments for millions of people based on such a small trial, regardless of its quality. “This is insane!” tweeted Gaetan Burgio, an Australian National University expert on drug resistance, noting what he sees as lapses in the 6-day trial, including inconsistent testing of virus levels in the patients.

    To Dahly and others, only much larger, better studies such as one WHO has just started can show whether any optimism about the compounds is warranted. “The best way to know whether a medication for COVID-19 is effective is through a high-quality clinical trial,” says Joshua Sharfstein, a vice dean at Johns Hopkins University’s Bloomberg School of Public Health and a former principal deputy Food and Drug Administration commissioner. “Efforts to widely distribute unproven treatments are misguided at best and dangerous at worst.”

    Such cautions were buried under an avalanche of demand for hydroxychloroquine, also sold under the brand name Plaquenil, and chloroquine, as doctors rushed to prescribe one or the other for confirmed or possible COVID-19 infections. Among the immediate consequences:

    Shortages of the drug are endangering patients who need it for lupus or rheumatoid arthritis.

    India, a major producer, has banned exports, and some doctors are hoarding both drugs by writing prescriptions for themselves or family members.

    Deaths in Nigeria among people self-treating for apparent COVID-19 were attributed to chloroquine overdoses, and an Arizona man trying to avoid COVID-19 infection died after reportedly self-medicating with a toxic form of chloroquine used to clean fish tanks.

    Brazilian President Jair Bolsonaro, a staunch Trump ally, ordered that nation’s military labs to ramp up production of chloroquine. Panic buying has ensued.

    “Here in Brazil even good scientists are backing this, saying we should waive rigor in difficult times,” says Natalia Pasternak Taschner, a microbiologist at the University of São Paulo, São Paulo. “We should be even more rigorous lest we give people false hope and invest [limited] time and money on unwarranted claims.”

    Although doctors regard hydroxychloroquine as relatively safe at prescribed doses for short periods, it has been associated with life-threatening cardiac side effects and suicidal behavior. “Given the toxicity of the drug, I’m afraid my government is going to kill people,” Taschner said.

    Trump’s initial public remarks on the drug candidates at a 19 March briefing appeared to be based on anecdotal reports from China and the tiny French study, which Vanity Fair reports he learned of after Elon Musk tweeted about it and Fox News amplified the information. In that trial, the Mediterranean Infection University Hospital Institute (IHU) treated 26 COVID-19 patients with hydroxychloroquine alone, or combined with the antibiotic azithromycin. The authors reported “clearance”—no virus present in samples taken by nasopharyngeal swabs—in most of them, but continued infection in most of a 16-person control group of COVID-19 patients. The patients who received both drugs cleared the fastest, the researchers reported in a peer-reviewed paper in the International Journal of Antimicrobial Agents.

    Many scientists have criticized the French trial as riddled with enough methodological flaws to render its findings unreliable or misleading. Biostatisticians from the United Kingdom and Ireland cited a basic failure: Investigators didn’t randomize the groups—essential to ensuring dependable comparisons. They also noted that six of the treated patients were lost to the study, five of whom fared badly—one died, three entered intensive care, and one stopped treatment because of nausea. Yet they were dropped from the analysis, potentially skewing the outcome.

    Elisabeth Bik, a scientific integrity consultant, wrote on her blog that for some patients supposedly helped by the treatments, daily tests for the presence of the coronavirus fluctuated between positive and negative, suggesting the virus might have persisted, just below the test’s detection threshold. Investigators should have confirmed viral clearance over two or three consecutive days, she said, particularly because the trial did not keep track of clinical indicators such as fever or shortness of breath. But the viral tests also ended after no more than 6 days total for all patients.

    Bik and other researchers have raised questions about other aspects of the paper, including its peer review, noting the submission and acceptance dates suggest it was reviewed in less than 24 hours. One of the paper’s authors is also the journal’s editor-in-chief, which Bik says might be “perceived as a huge conflict of interest.”

    Chloroquine may be as effective as the French trial suggests but we need bigger and better research before we jump the gun.

    Fair comment, the reality show President belittling rhetoric is seriously misinformed. There is significant reason to take this seriously, though the talking points and partyline of the bulk of international and esp US media would not lead you to think so.

    My impression is that the hopes for chloroquine are being taken very seriously

    And if my rhetoric is belittling it is as nothing compared to the belittling nicknames and rhetoric that Trump routinely directs at anyone he perceives as an opponent. And he is President where I am not, which means that he has a higher duty to the country than pursuing petty feuds.

  37. 37
    kairosfocus says:

    Sev, FYI the yet further development is that France has now approved the drug once this test was on the table and that a group of pharmaceutical companies has indicated they will produce 250 million tablets by mid April. There is now, cumulatively, a growing body of evidence, clinical reports and statistical tests strongly pointing to efficacy of HCQ especially in a cocktail with Z-pac [and with Zn supplements]. As such evidence mounts, the chances that such is by chance drops exponentially. KF

    PS: I note, that by end of February to early March, there was already a considerable body of evidence of effectiveness on the table, as I have partly documented from a series of OPs here. Note, this specifically includes tests documented in the professional literature from 15 Years ago, post SARS, that Chloroquine was effective chemically against a broad range of RNA and DNA viruses. As it is a well studied and widely used drug, the translation between chemical and in vivo effectiveness should have been recognised. The REAL scandal and debate we should have been having — given the longstanding, pressing need for effective antivirals — is why there was not a concerted effort to test and approve it over a decade ago. I suggest, that it is a longstanding generic and that approvals processes are now extremely cumbersome and costly just might have something to do with that.

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