Will we finally have the right to talk about hydroxychloroquine in good faith?
In almost all my posts regarding COVID-19, I mentioned the defamation campaign against the hydroxychloroquine (HCQ). Could we now conduct fair trials and stop censoring the truth? We finally got the right to blame the Chinese, but this isn’t enough.
It’s Didier’s
I’m reusing as the OG Image for this post an image from April 2020, when le Professeur Didier Raoult was “my hero.” In my impossibly long posts on the matter, there’s so much information that nobody bothered to read them thoroughly, so I’ll summarize my point on the HCQ succinctly:
- It’s not “Trump’s miraculous drug.”
- It’s not “Dr. Zelenko’s protocol”: hydroxychloroquine (HCQ), zinc (Zn), and azithromycin (AZM).
- It’s “Dr. Didier Raoult’s protocol”: hydroxychloroquine (HCQ) and azithromycin (AZM).
- The zinc is not useless, but it’s merely an adjuvant, less effective in modulating the immune response and the cytokine storm than Vitamin D (or the Vitamin D plus Vitamin K combo).
- As per Dr. Raoult, the treatment should be administered from the early stages of the disease, not when the patient has no chance to recover lung’s function. Most studies who labeled HCQ as ineffective only started administering it when it was too late.
- Also as per Dr. Raoult, HCQ must be associated with AZM. This is not to prevent additional bacterial infections in the respiratory tract, but because of the paradoxical antiviral effect of this antibiotic. Many studies only used HCQ.
- HCQ is known, initially as chloroquine phosphate or sulfate, since 1934. It has been used by about 2 billion people to prevent or treat malaria, or in autoimmune diseases such as systemic lupus and rheumatoid arthritis. It’s a very safe medicine included in the WHO Model List of Essential Medicines. However, as all drugs, there are specific contraindications, and there are toxicity limits. To prevent malaria, the dosage starts at 200 mg HCQ (base) per week. 600 mg/day should be a safe dosage for people of 60+ kg. Most clinical studies meant to discredit the use of HCQ in COVID-19 have given patients up to 2,400 mg HCQ per day, which is a deadly dose that would kill 20% of the healthiest people even without a SARS-CoV-2 infection!
- Dr. Raoult’s had only a handful of deaths among his COVID-19 patients at IHU Méditerranée Infection because his patients were constantly monitored (oxygen saturation, blood coagulation, etc.) and treated from the beginning, not left at home with paracetamol, as most protocols in most countries did, in the most genocidal way!
A new study
Now there is a new observational study that suggests HCQ+AZM was helpful from the very beginning! Sorry to give a Link to Daily Mail, but this is how I found about it: Was Trump right about hydroxychloroquine all along? New study shows drug touted by former president can increase COVID survival rates by 200%. You should prefer the actual study (full PDF): Observational Study on 255 Mechanically Ventilated Covid Patients at the Beginning of the USA Pandemic.
- This observational study looked at 255 COVID-19 patients who were admitted in the Saint Barnabas Medical Center in Livingston, New Jersey, by May 1, 2020, and which required invasive mechanical ventilation (IMV), but the study has been made available in preprint on May 31, 2021.
- The patients had pre-existing conditions aka comorbidities: hypertension (63.5%), diabetes (59.2%) and obesity (50.4%). By discharge or by day 90, 78.2% of them died. However, the comorbidities and clinical status on presentation were not predictive of the outcome. The mortality rate of 78.8% is similar to published data on critically ill COVID-19 patients from February through June 2020, but lower than that of other studies.
- Treatment schemes: steroid therapy (dexamethasone), tocilizumab (TOZ), convalescent plasma (CP), HCQ alone (≥400 mg), and HCQ and AZM.
- Patients receiving >3g HCQ and >1g AZM had 3.26 times lower risk of death than those who did not receive these doses.
- Patients receiving TOZ had 2.00 times lower risk of death than patients who did not receive the medicine.
- Patients who received ≥6 mg dexamethasone for at least 3 days had 1.42 times lower risk of death.
This should be enough per se, but there’s a discussion to be made about HCQ and AZM:
When AZM and HCQ were given together, the association with survival greater than when HCQ was given alone. We finally noticed that patients, who received cumulative doses HCQ > 3,000 mg and AZM > 1,000 mg, had a much higher survival rate than all others. 37 patients received > 3g HCQ and > 1g AZM. 18 patients (48.6%) of these 37 patients survived. Comparatively, 36 patients (16.5%) of 218 patients who received either <= 3g HCQ or <= 1g AZM survived. The absolute difference (32.1%) in survival was significant [C.I = 15.9% – 48.2%; p <0.0001]. The relative difference in survival = 194.5%. Differences of these magnitudes have not been reported in other clinical studies.
Also:
Most Covid studies have not considered days of therapy, cumulative dose, or weight-adjusted dosing. We found that when the cumulative doses of two drugs, HCQ and AZM, were above a certain level, patients had a survival rate 2.9 times the other patients. By using causal analysis and considering of weight-adjusted cumulative dose, we prove the combined therapy, >3 g HCQ and > 1g AZM greatly increases survival in Covid patients on IMV and that HCQ cumulative dose > 80 mg/kg works substantially better. These data do not yet apply to hospitalized patients not on IMV. Since those with higher doses of HCQ had higher doses of AZM, we cannot solely attribute the causal effect to HCQ/AZM combination therapy. However, it is likely AZM does contribute significantly to this increase in survival rate. Since higher dose HCQ/AZM therapy improves survival by nearly 200% in this population, the safety data are moot. However, given the data presented here, the studies reporting HCQ’s effect of QTc intervals need to be reevaluated.
The QTc interval thing, in plain terms: there was no correlation between HCQ cumulative dose and QTc delta, i.e. the ECG showed no negative effect of the HCQ on the heart!
Stephen Smith, one of the authors of the study, added a few comments of relevance. The first one concerned the cumulative dose:
The most commonly used cumulative dose of HCQ = 2,400 mg. This dose/regimen was recommended, as noted in the paper by Yao et al., based upon computer modeling. The 2,400 mg dose was given over 5 days, 800 mg on Day 1 and 400 mg on Days 2-5. The treating or consulting ID physician chose the cumulative dose.
In late March, the French data came out and some switched to the French regimen, 600 mg of HCQ x 10 days plus azithromycin x 5 days. Most pts received the 800 mg first day dose, which was started by the ER docs and was a click in the computer ordering system. The ID docs saw the pt the next morning. Many continued the pt on 400 mg per day for 4 more days. Others switched to 600 mg per day. So, by Day 5 on the latter regimen, the cumulative HCQ dose = 3,200 mg or > 3 gm or the cut-off used in our paper. In other words, it took just as long to get to > 3 gm and as it took to get to 2,400 mg.
From the second one:
BTW, I have no idea why Dr. Raoult added AZM to the HCQ regimen. But at the time, those were the only clinical data available. So, we used that regimen. We then realized that the weights of pts varied enormously. So, we started aiming for 80 mg/kg cumulative dose of HCQ (6,000 mg HCQ divided by 75 kg or average adult weight). But overall, the data strongly suggest that AZM co-administration is needed to achieve this success in increased survival.
From the third one:
First, you don’t have to get to 10 days to receive >3 gm of HCQ and >1 gm of AZM. We gave 600-800 mg per day.
…
Listen, I didn’t expect to see these huge differences. But the fact that weight-adjusted HCQ dosing correlated with survival even stronger than cumulative dose is extremely strong evidence that HCQ/AZM were the cause of that difference. Younger pts were much heavier than older pts. Consequently, weight-adjusted HCQ cumulative dose shifted younger pts to a relatively lower dose and older pts to a relatively higher dose. That introduces a strong bias against weight-adjusted HCQ being associated with survival. Despite this bias, weight-adjusted HCQ cumulative dose was more strongly associated with survival than cumulative HCQ dose.
Let’s recap the findings:
- The most effective is the HCQ+AZM combo. It cuts the risk of death by 3.26.
- The cumulative dose is important (>3 gm of HCQ and >1 gm of AZM).
- The daily dosage must be adapted to the weight of the patient, as to avoid the side effects!
- Correctly administered, the HCQ doesn’t hurt the heart.
Honestly, I don’t expect the powers that be (including Big Pharma) to admit their immoral vileness, but I’m not an optimist by nature. The common sense of the public isn’t great either–it was the public who launched thousands of fake news, and it’s the public that is now, in some countries, hysterical about getting AstraZeneca’s and Janssen’s (J&J) vaccines completely retired from use. Only time will tell what comes next (a 4th wave?).
Clarification: I don’t hold for Didier Raoult any cult-like veneration. I watched most of his public appearances and, if we were to judge by his body language, one could say he’s a pathological liar or someone trying to deceive. But when the facts suggest otherwise, I’ll stick to the facts, not to the individual.
Making sense
Also, it helps when it does make sense. In the case of the HCQ, its inhibitory effect on the cytokine storm by suppressing T-cell activation is well-known from before the pandemic. Any immunomodulatory therapy able to down-regulate the cytokine storm helps in COVID-19, and I’ll mention again the mild helpful effect of the Vitamin D.
Under the circumstances, the fact that the French authorities have forbidden the general practitioners to prescribe HCQ, a drug that was prescription-free (OTC) before January 15, 2020 (see here), is literally genocidal! If I were their mentally retarded Olivier Véran, I’d have done rather the contrary: I’d have distributed rationing tickets for one 200 mg Plaquenil pill per week per adult, and then, when people got positive, I’d have made this study:
- How many people who took HCQ as if they were trying to prevent getting malaria got infected with SARS-CoV-2, compared to those who didn’t take HCQ and got infected?
- How many of them had severe symptoms?
- How many of them needed hospitalization?
- How many of them needed invasive medical ventilation?
- How many of them died?
I’m sure the results would have surprised everyone. Everyone but me and Didier Raoult.
LATE EDIT: The “official” anti-vaxxers
As much as I hate Big Pharma, and as much as I hate the pharma regulators such as the European Medicines Agency, a bureaucratic cesspool of idiots who have forbidden dozens of classical, proven drugs because one idiot in ten million “might” develop a certain condition, I find the current official anti-vax trend disgusting.
Linguistic note: anti-vax, adjective; anti-vaxxer, noun.
We’re still not free to say that children can transmit the disease the same as the adults, if not more; on the contrary, we have this:
JUST IN – German scientific vaccination commission (STIKO) advises NOT to vaccinate healthy children against #COVID19, only severely pre-diseased children.
— Disclose.tv 🚨 (@disclosetv) June 10, 2021
Pre-diseased: German STIKO recommends vaccinations against coronavirus only for 12 to 17-year-olds with certain rare preexisting conditions.
— Disclose.tv 🚨 (@disclosetv) June 10, 2021
The, we have this:
JUST IN – CDC to hold an “emergency meeting” on rare but “higher-than-expected” reports of heart inflammation following jabs of the mRNA-based Pfizer and Moderna #COVID19 vaccines (CNBC)
— Disclose.tv 🚨 (@disclosetv) June 10, 2021
Here we go again on the lines of the AstraZeneca “scandal” regarding blood cloths. Here too, the devil is in the details:
So far, the CDC has identified 226 reports that might meet the agency’s “working case definition” of myocarditis and pericarditis following the shots, the agency disclosed Thursday. The vast majority have recovered, but 41 had ongoing symptoms, 15 are still hospitalized, and 3 are in the intensive care unit.
The reports represent just a tiny fraction of the nearly 130 million Americans who have been fully vaccinated with either Pfizer or Moderna’s doses.
226 cases (at most!) in 130 million makes 1.7 in a million. The unanswered question: what is the normal incidence rate of myocarditis/pericarditis in a given population within the same age brackets? Unless we know the answer to that, the whole story is scaremongering.
With AstraZeneca, they used some old figures to say that the incidence of blood cloths was more important than the “natural” values. But they used data from the pre-pandemic past, when people lived under less stress, and they didn’t have the proper statistics per age groups in all the affected countries.
Either way, what are the “normal” numbers for myocarditis/pericarditis in the US population? Just like with AstraZeneca, I’d suggest a social experiment: give everyone a free sausage, register them, and then count how many of them develop conditions that might meet CDC’s “working case definition” of myocarditis and pericarditis!
Changing the conditions of the experiment, we might be surprised to reach pointless but “scientifically valid” conclusions such as:
- Sausages can lead to 2 cases per million of myocarditis or pericarditis. Let’s ban them!
- Wearing socks can lead to 2 cases per million of myocarditis or pericarditis. Let’s ban them!
- Reading a free newspaper can lead to 2 cases per million of myocarditis or pericarditis. Let’s ban them!
Not all vaccines are born equal (read about some failures, from manufacturing Dr. Salk’s anti-polio to Sanofi’s Dengue vaccine in section SEVEN here), and we can all agree that in this pandemic everything has been rushed-in, but the overall approach is unscientific and against the common sense.
BONUS: No, the spike protein in the mRNA vaccines isn’t toxic!
Apparently, the anti-vaxxers will never stop creating fake news and FUD (fear, uncertainty and doubt). Please read the truth:
- Byram Bridle’s claim that COVID-19 vaccines are toxic fails to account for key differences between the spike protein produced during infection and vaccination, misrepresents studies
- USA Today: Fact check: COVID-19 vaccines don’t produce dangerous toxins / Reuters: same fact check
Both article are very well documented, please spend some time reading them. You’ll understand that it’s terribly easy to make unsubstantiated claims and some people would fall for them.
I’m sick of the stupidity of the global populace.
👉 Continued here.
The moment of truth: No, we won’t have this right!
Big Pharma takes revenge!
- Marseille : l’IHU du professeur Raoult perquisitionné lundi
- À Marseille, des perquisitions menées à l’IHU du professeur Didier Raoult
- Marseille : L’IHU Méditerranée du professeur Raoult perquisitionné
Only a complete idiot would believe that this has nothing to do with Didier Raoult’s positions. Oh, la Justice de la Cinquième République, pas comme les autres. Yeah, sure.
Updated with two more topics.
Big Pharma takes revenge!
“randomized, placebo-controlled trial”: newsroom.uw.edu/postscript/end-hydroxychloroquine-treatment-covid-19
“There was no faster resolution of symptoms among people receiving hydroxychloroquine or hydroxychloroquine/azithromycin compared to placebo.” Johnston said.
Don’t. Just don’t. One single study, I can piss on it. I won’t even read it. I wrote more than once: HCQ, as Didier Raoult said, should be administered in/from the very early stages of the infection, otherwise it’s useless! It’s easy to make a study saying it doesn’t work if you administer HCQ to patients with destroyed lungs!
But HCQ’s only effect is to prevent the cytokine storm that makes your body destroy your lungs! I suppose this could work preventatively too, the way it works against malaria.
The anti-inflammatory effects of the HCQ are used e.g. in rheumatoid arthritis. The way it prevents your body to destroy itself is used in some autoimmune diseases such as lupus. It’s not uncharted territory!
The medrxiv preprint you analyzed is also a single study and has all the known biases of observational ones. I don’t know if Dr. Raoult is a liar, but his publication list shows that he has no or very little experience with clinical trials. Why would anyone believe that his claims about giving HCQ early are anything else than pure invention ?
About the medrxiv preprint: https://www.factcheck.org/2021/07/scicheck-no-new-revelation-on-hydroxychloroquine-and-covid-19/
Too much money has been already invested in trying to understand whether HCQ could have a benefit in COVID-19 to ask for more studies. It does not. Asking for more studies is similar to what homeopaths are doing all the time: “nah, we don’t have any evidence that homeopathy works, but it’s only because the studies have not been done in good faith”.
Finally, there is no evidence that, as you wrote, HCQ could prevent the cytokine storm in Covid-19. The immunomodulatory effects of the drug were only observed after months of administration in chronic illnesses and even there, the evidence for clinical benefits remain weak because studies used only a few dozen patients (see this Cochrane analysis on the drug effects in lupus: https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD007478.pub2/full).
The Covid pandemics highlighted the weaknesses of clinical research and how easy it is to draw bold conclusions from biased results.
1. You definitely know very little about Dr. Raoult’s past. Please get informed.
2. factcheck.org is so skeptical about anything and everything that, if we were to apply the same “high standards” to all claims for all drugs, then more than half of the prescription drugs would get banned, and more than half of the OTC drugs would be reclassified as dietary supplements.
3. Do you know people having lupus? I do. Do you know people having, dunno, cancer, and who take all the drugs that might help, as long as they’re prescribed to them?
It’s like saying, “oh, but the aspirin and the paracetamol don’t always have the intended effect, so let’s say they’re crapola!”. No, it doesn’t fucking work that way.
Thank you for taking the time to answer to my comment. I did not expect arguments to change your point of view.
1. I hate authority arguments, but, as a scientist, I am pretty sure that Dr Raoult’s laboratory scientific production is below standards in the field. The committee of experts examining his institute’s science had a similar opinion. Favoring quantity over quality is not how this should be done. So, yeah, I’m not guessing here, just stating facts.
3. It is a tragedy that desperate people, having cancer or other severe illness, are ready to try anything in search for a cure. I said that only small clinical trials have been done to see whether HCQ was effective in lupus. It might work, and the drug is prescribed in lupus. The fact that you personally know a few people with lupus does not make you an expert in the field of immunomodulation, nor does it explain anything about the similarities between the potential effect of HCQ in lupus and the physiopathology of Covid-19.
The analogy with aspirin or paracetamol is strange, since these drugs work pretty well on everybody, to decrease fever, for example. I don’t know what you meant by “intended effect”, but these drugs are effective antipyretics. You could do any time a new controlled clinical trial on these drugs, and they would work (like antibiotics on sensitive bacteria, calcium channel blockers for hypertension or histamine receptor blockers for allergic reactions).
1. Malaria, tropical diseases, field experience in Africa: Dr Raoult has a huge hands-on experience. In Africa, not in Marseilles. I very much value this kind of experience, the same way I appreciate a mechanical engineer whose engineering expertise is not only “mouse-based” (if you know what I mean). Medicine is not mathematics, it’s not just theory and lab.
2. Paracetamol works very well in killing your liver. For an antipyretic, when the maximum recommended daily dosage of paracetamol HAS NO EFFECT WHATSOEVER (it happened to me more than once, the fever simply stayed at 38.5-38.6°C!) the best effect comes from sodium metamizole (Novaminsulfon, Dipyron, Анальгин, Algocalmin) or magnesium metamizole (Nolotil), now banned in several Western countries (starting with the late 1970s), and available by prescription in others, after having been tremendously successful around the world for many decades, usually as an over-the-counter drug (at least in Russia, Romania; it’s still very popular in Mexico, yet illegal in the US). The reason? A tiny risk of agranulocytosis and neutropenia. Heck, I knew someone who took 4 grams a day for about 20 years, the person having several severe morbidities, and it was just fine. After all, the patients of risk should be monitored, and everyone should know themselves and notice if they don’t tolerate well a drug. Nobody died suddenly after having taken metamizole!
3. I sincerely don’t believe there’s a single scientist left in the pharma and health care fields! They’re all stupid bureaucrats, and experts in statistics. I wrote about many other effective drugs that have been banned and discontinued, or severely restricted, or that are approved in the EU but not in the US, or vice versa. Stupid bureaucracy. So a “scientist” like you and a bureaucrat decide a drug is “effective enough and safe enough” in a given developed Western country, but their counterparts in another developed Western country decide quite the contrary. THIS IS NOT SCIENCE.
Side note: The Roter tablets, used in Western Europe since the late 1940s, were extraordinarily effective in the treatment of peptic ulcers (my father was saved from a surgical operation by Roter in the late 1960s), and was later produced in Romania as Ulcerotrat; it was also magical in the cases of acid reflux with dyspepsia, but it’s now banned in the “civilized countries” because one of its ingredients, the bismuth subnitrate, is “highly toxic” (yeah, I didn’t know why I died and I’m now a zombie: I also took it for quite some time). It’s still manufactured in Hong Kong. However, if the bismuth subnitrate is a no-go, somehow the bismuth subsalicylate is “good”… as it’s what PeptoBismol contains, and Pepto is very much the norm in the US!
We could also talk of drugs such as: Diane-35, Celebrex (celecoxib), Vioxx (rofecoxib), Arcoxia (etoricoxib, it’s magical, trust me!), the formaldehyde or formol (a very popular drug, Formitrol, doesn’t contain it anymore, despite dozens of millions having taken it without any problem), fusafungine (Bioparox, Locabiosol), etc. etc.
Since you’re in the field, could you solve the mystery of the best antipyretic ever (however, with no analgesic effect), Acalor? It might have been orthoxyquinoline sulfonate of aminophenazone (a natrium salt of aminophenazone with the 8-hydroxyquinoline-5-sulfonic acid), but I can’t tell for sure; nor could I know why was it banned, except that rumours were circulating that it was also used to induce an abortion. Was it banned for being related to aminophenazone (Pyramidon)?
EDIT: Are you that guy from Pasteur? If so, why are you interacting on blogs with “laymen”? Experts being experts, they’re also known to be inflexible. Sort of a tunnel vision in itself, pour ainsi dire.
I enjoy reading your criticism of many aspects of the Linux and computer-related world and I have many views that are similar to the ones you express here, or in the past, in the “Béranger” days. It’s sad that your vision of experts is so far from reality. How many experts do you know ? Why do you hold “experts” to such a low level of esteem ? The term “inflexible” does not go well with most people who have the chance to do research. If you are inflexible you are not doing science. And good medicine is based on good science.
It’s your blog, your space, and I just feel sad that an intelligent person has been manipulated by people such as Raoult into believing the HCQ hoax. You invested in this belief and it will require a gigantic effort to get out of this. It is maybe even impossible and you are going to hate me for even mentioning it.
That there are enormous problems with the Big pharma et al., it’s obvious. Families of new drugs are not developed by pharmaceutical companies because the “market” is not interesting enough (mostly acute infectious disease). The process of approving or not a drug for use is complex and flawed. Still, the quality of the published studies has to be evaluated for each case, and try to see which studies were carefully done and which are trash.
As much as I enjoyed discussing with you through these messages, I hope you will agree that we might need to disagree on a few topics. Maybe we can find common ground for interesting discussions some other time. Best regards,
I know experts in software development, electronics, mechanics, law. Most of them are either morons, or frauds. It can’t be any different elsewhere.
Does Bologna tell you something? Isn’t everyone having a “minimum quota” of required publications if they want a PhD, a tenure/professorship, or whatever? There are hundreds of thousands of contradictory, irreproducible, and useless “studies” — published ones. In prestigious scientific magazines, no less.
Today, a study says the aspirin is good in preventing heart issues. Tomorrow, a study (observational?) says the contrary. The same for coffee and cancer (one study: it helps preventing it; the next one: it might cause it!), and for many other common topics.
How can one still trust such (haha, “peer reviewed”; why not “ISO 9001”?) studies and, subsequently, people such as those who wrote them?
EDIT: Regarding the HCQ, I’m an agnostic, not a believer. You claim to know everything about it, but I just ask questions, and I don’t like the “holy war” against it, which started even before any study was made. It’s when they first made it prescription-only in France, then they forbade “les médecins de ville” to prescribe it. This is fascism (or communism, as both impose their only truth). (I am for the right of anyone to take whatever they want: cannabis, because it’s made by nature, and nature cannot be made illegal; strychnine or whatever they want; and also those drugs that are prescription-only, if they assume the risk, and if they don’t drive, they don’t pilot planes, etc.)