> Today, three of the authors of the paper, "Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis", have retracted their study. They were unable to complete an independent audit of the data underpinning their analysis. As a result, they have concluded that they "can no longer vouch for the veracity of the primary data sources."
"Our study has several limitations. The association of decreased survival with hydroxychloroquine or chloro-quine treatment regimens should be interpreted cautiously. Due to the observational study design, we cannot exclude the possibility of unmeasured con-founding factors, although we have reassuringly noted consistency between the primary analysis and the propensity score matched analyses. Nevertheless, a cause-and-effect relationship between drug therapy and survival should not be inferred. These data do not apply to the use of any treatment regimen used in the ambulatory, out-of-hospital setting. Randomised clinical trials will be required before any conclusion can be reached regarding benefit or harm of these agents in COVID-19 patients. We also note that although we evaluated the relationship of the drug treatment regimens with the occurrence of ventricular arrhyth-mias, we did not measure QT intervals, nor did we stratify the arrhythmia pattern (such as torsade de pointes). We also did not establish if the association of increased risk of in-hospital death with use of the drug regimens is linked directly to their cardiovascular risk, nor did we conduct a drug dose-response analysis of the observed risks. Even if these limitations suggest a conservative interpretation of the findings, we believe that the absence of any observed benefit could still represent a reasonable explanation.In summary, this multinational, observational, real-world study of patients with COVID-19 requiring hospitalisation found that the use of a regimen con-taining hydroxychloroquine or chloroquine (with or without a macrolide) was associated with no evidence of benefit, but instead was associated with an increase in the risk of ventricular arrhythmias and a greater hazard for in-hospital death with COVID-19. These findings suggest that these drug regimens should not be used outside of clinical trials and urgent confirmation from randomised clinical trials is needed."
Has anyone seen good randomized clinical trials yet?
To people who believe the current political rhetoric promoting hydroxychloroquine, a study in a medical journal doesn't change anything, as their interest in it was never based its medical efficacy, but rather as a symbol used to rally around their leader and their movement. Just look at the anti-vaccination movement, which continues despite being debunked for years.
And we shouldn't so quickly dismiss this phenomenon. We underestimate the power of that kind of fictional narrative group-think to our peril. The only way to fight falsehood based narrative is truth based narrative. The dry statistical or scientifically derived truth that eggheads like most of us wish would prevail is largely powerless. Stories are what ultimately wins.
Those of us who live in the world of reality need to realize the only way to fight this "demon haunted world" is to make a scarier demon, not try to fight with facts.
31 years in India and I've never even heard of it!
Europeans were extra stupid to try it as treatment. If you read the early original Chinese reports they always mentioned that it worked as prevention, Lupus patients had an advantage.
And those two disliked presidents always promoted its usage as prevention, not treatment. But reading is apparently a rare skill.
Irrational behavior in both directions is indefensible.
Agreed that any political side is capable of false narratives, but that's hardly what's going on here. Nobody with the fundamental desire for a treatment for themselves and those they care about should they fall severely ill would want any proven effective treatment to be dismissed for political reasons, whether that is hydroxychloroquine or anything else.
The problem is that what should have been left as an investigation into a medication with no political colors was turned into a political wedge by the US president who seemingly aspired to use it to regain relevance during this crisis.
The same thing has also happened for the various promotions of very preliminary vaccines, or of a fictional nationally deployed testing website that was claimed by POTUS to be under development by Google. This follows the basic principle guiding this administration and its leader that there is no such thing as bad publicity. And to a certain extent, they might even be right. Time will tell.
If you look at the experts, they're still designing studies to test it, and there are some papers suggesting it does work. The jury is very much still out on this subject.
I'd like nothing more than for hydroxychloroquine to be an effective treatment, so we can end this crisis. It should continue to be explored and investigated. At the very least we might learn something new that will help with its known effective use in treating malaria or autoimmune diseases like lupus.
But it should never have been turned into a political football, and the person responsible for that is unmistakably the POTUS.
 (video) https://fast.wistia.net/embed/medias/td0v8taipc
There was an article the other day that interviewed someone who’d been on long-term treatment with the drug (for lupus) they were shocked when they got covid, because they believed that the drug was a prophylactic. No reputable scientist ever claimed that, as far as I know; it was a popular myth encouraged by unscrupulous news outlets, which won’t go away just because of a study or two.
It may be the end of the road for hospitalized patients with heavy viral loads but, considering the fact that zinc is mentioned nowhere in the full text, it is not the end of the road for prophylaxis. Early action before hospitalization is necessary... see below.
Zinc does the hard work of inhibiting viral replication; HCQ is the zinc ionophore that lights the pathway. "First used in 1967, the term ionophore refers to the molecule’s ability to bind a metal ion and facilitate its transport across cellular membranes." In order to inhibit viral replication, zinc must enter the cell... HCQ and other zinc ionophores can facilitate this.
Pasting my previous comment below with slight modifications:
Hydroxychloroquine is just one of several zinc ionophores that inhibit viral replication. "Zinc Ionophores Pyrithione Inhibits Herpes Simplex Virus Replication"
"... the virus replicative cycle can be divided into 10 steps (Fig. 52-1): (1) adsorption, (2) penetration, (3) uncoating, (4) early transcription, (5) early translation, (6) replication of the viral genome, (7) late transcription, (8) late translation, (9) assembly, and (10) release of new virus particles."
If using HCQ as a zinc ionophore which targets replication, "antiviral drug treatment should be started early, before irreversible tissue damage occurs. Such timely treatment is not possible without early and accurate diagnosis, which is difficult for many viral infections (such as infections of the respiratory tract)"
Edit: Wow, how the HN community has fallen. Downvoting a simple, honest question into oblivion.
HCQ is an enabler; zinc does the heavy lifting but only if administered early.
See my other comment downvoted to oblivion below.
Admit you were wrong.
https://www.thelancet.com/journals/laninf/article/PIIS1473-3... is an overview of the counter criticism on it, with a link to the study.
A computer programmer suggesting a medical study shouldn't be given much credit based on a question they self-admittedly don't understand is pretty far from my definition of humility.
"Asking a simple question" is different from "asking a question and supplying your own assumed answer and throwing the whole thing out as a result."
> If zinc is not a `macrolide` I wouldn’t give this paper much credit as they didn’t test the treatment properly.
Also where did I claim anecdote was a good way to conduct medical research? I did not. Anecdotal evidence is a completely valid source to find ideas that might be worth trying and testing with actual research.
I don't need any answer your points because you've not given any evidence to suggest they should be taken seriously versus the evidence that two-thirds of the treatment you suggest is still quite harmful.
Are you suggesting I should trust everything the government, media, or scientists says whole cloth simply because I am not an expert? Sorry, that is not how I operate or ever will operate. I take information on all sides of every topic seriously and come to the best conclusion I can for myself and I share what I’ve seen and learned with others.
If you don’t like that move to China and enjoy the CCP.
If you were an alien on another planet, would you blindly trust the local populace about things you did not understand? If not, why does that suddenly change when you are your own planet among your own people?
If you can't understand the logic of a solution posed to you, then logically you must not accept it as absolute fact.
Improving the efficacy of Chloroquine and Hydroxychloroquine against SARS-CoV-2 may require Zinc additives - A better synergy for future COVID-19 clinical trials
Zn2+ Inhibits Coronavirus and Arterivirus RNA Polymerase Activity In Vitro and Zinc Ionophores Block the Replication of These Viruses in Cell Culture
Does Zinc Supplementation Enhance the Clinical Efficacy of Chloroquine/Hydroxychloroquine to Win Todays Battle Against COVID-19?
Zinc ionophores have been shown to inhibit replication of various viruses in vitro:
Equine viral arteritis
Hepatitis C virus
Herpes simplex virus
Human Immunodeficiency Virus
All doctors I’ve seen promote hydroxychloroquine have been adamant that it must be administered early in the disease’s progression in order to have any effect.
But most of the studies being performed that I’ve heard of, have explicitly been on late-stage patients. This includes the central EU study.
It would be tragic if the drug works when administered early, but all the studies have happened at a late stage, incorrectly disqualifying a treatment that can save many lives.
I'm sure a test group could be made among them to test for severity of symptoms + testing to see the number who are later hospitalized.
How would you justify giving hydroxychloroquine to hundreds of thousands of healthy people a year for malaria prophylaxis?
I'd expect the lungs to be fully invaded and serious damage done by the virus by that time. This is not an early, or even seriously prompt, treatment. Certainly if the patients were in a hospital setting this would be unacceptably slow treatment.
This appears to be yet another of several "studies" where HCQ was given late to patients that were already near death. Of course it had little effect.
The recommendation was always HCQ + AZITHROMYCIN + ZINC SULFATE given EARLY. Few, if any, studies have followed that recommendation.
I don’t get it. Just do a simple, proper frickin’ study where the cocktail you mention is used immediately after diagnosis, and compare outcomes with different treatments.
This seems so obvious that I wish someone could point out to me what obvious detail I’m not understanding. It’s as if proving Trump wrong is more important than answering the real and important yes/no question.
So it’s sadly not very useful for drawing conclusions about that :(
Another drug that doesn't work nearly as well as some people think. https://www.bmj.com/tamiflu
> The reviewers concluded that there was no convincing trial evidence that Tamiflu affected influenza complications (in treatment) or influenza infections (in prophylaxis), and raised new questions about the drug’s harms profile.
Everything needed for FDA approval.
> no convincing trial evidence
It just sounds like Tamiflu efficacy studies to date haven't been thorough enough to be convincing.
Conclusion: This study provides the first in vivo evidence that zinc sulfate in combination with hydroxychloroquine may play a role in therapeutic management for COVID-19.
This one is underway:
That's great but that doesn't exactly tell us that hydroxychloroquine + zinc is better than other therapies or even better than nothing.
The clinical trial is regarding the efficacy as a prophylaxis for a small portion of the population that is most directly exposed. It would be great if it works but it will likely not be as useful as a treatment as we can't necessarily give our whole population a years worth without seeing other health consequences.
One might ask pointed questions why the original formulation (zinc + ionophore) is so consistently absent from these studies. I don't care one way or the other about the drug, but why are studies widely promoted that are irrelevant to the question?
For something purporting to be the current consensus of evidence-based medicine, it sure lacks the usual hallmarks of scientific inquiry: openness, transparency, review.
Edited to add: Plus, that anonymous Google doc doesn't even represent the latest research, because the Raoult paper (under the heading "12 April 2020") has already been retracted: