Six months ago I wrote an article discussing the evidence on hydroxychloroquine as a treatment for covid. My conclusion then, based on the small number of trials that had been completed at that point, was that hydroxychloroquine did not appear to be an effective treatment for covid. Many of you were unhappy with that conclusion, and I’ve since then received multiple requests to look at the evidence again. So that’s what I’m going to do now.
A systematic review of randomized controlled trials was published by the Cochrane Collaboration a few weeks back. Unfortunately it only looked at data available up to mid-September 2020, so it’s missing more recent data. But it’s a good starting point for our quest to figure out whether hydroxychloroquine has any role in the treatment or prevention of covid.
I know some of you think we should be looking at the observational studies that suggest hydroxychloroquine is effective against covid. But those studies are rife with confounders, and I don’t think it makes sense to look at a lower quality form of evidence when a higher quality form is available. I often look at observational studies when it comes to nutrition, because higher quality data usually isn’t available. I don’t usually look at observational studies when it comes to medications, where higher quality data is available.
The reviewers identified ten trials that provided data on mortality, with a total of 8,270 participants. The trials varied in size from tiny to huge, with the largest study having 4,716 participants.
Two criticisms have frequently been levelled at the trials of hydroxychloroquine – that they gave the drug too late in the disease course to have an effect, and that they gave either a dose that was too low to have an effect or a dose that was so high that it was toxic. So let’s look at whether that was the case in these ten trials.
Two of the trials, with a total of 716 participants, started giving the hydroxychloroquine within three days after symptom onset. This is great. An additional three studies, with a total of 5,416 participants, started giving the hydroxychloroquine at around day six to nine after symptom onset. This might be too late to have an effect on the disease course. One trial, with 150 patients, didn’t give the hydroxychloroquine until around day 16 after symptom onset, which is almost certainly far too late to have any meaningful effect on the disease course (among those who die of covid, many have already died by day 16). The remaining six trials strangely didn’t report the average time point at which the patients received hydroxychloroquine.
Ok, so this is clearly a problem. If we think hydroxychloroquine needs to be given early in the disease course to have an effect, then only two of the trials clearly qualify for inclusion.
What about the doses given? Were they reasonable?
Hydroxychloroquine is primarily used to treat rheumatic diseases. A normal dose for these conditions is 400 to 600 mg per day. Most of the trials gave 400 to 800 mg per day, which is a reasonable dose, and unlikely to cause problems. One trial gave 1400 mg on day one, which is quite high, followed by 600 mg per day. The two biggest trials, with a total of 6,569 participants (in other words, 79% of all participants in the systematic review) gave the patients very high doses. One gave 1600 mg on day one, followed by 800 mg on the following days. The other gave 2,000 mg on day one, followed by 800 mg on the following days. These doses are much higher than those used for rheumatic diseases, and potentially high enough to induce toxic side effects. I guess these high doses could be motivated by the hope that you will have an increased probability of seeing benefit, but they also increase the risk of side effects significantly.
Both these trials did in fact show harm, with a 9% increase in the relative risk of death among those treated with hydroxychloroquine in one, and a 19% increase in the relative risk of death among those treated with hydroxychloroquine in the other. This harm could have been due to giving the patients a toxic dose. It’s certainly not possible to say what would have happened if the patients had been given a more normal dose.
Now we’re going to look at what results that Cochrane review had, but it’s clear that we’re also going to have to do some meta-analyzing of our own, to see what happens if hydroxychloroquine is given early, and also what happens if only non-toxic doses are given. So, what did the reviewers find?
There was a 9% increase in the relative risk of dying in the group treated with hydroxychloroquine, but it was not statistically significant. So, basically, the meta-analysis showed no benefit in terms of effect on mortality.
Now let’s see what happens if we do a little meta-analyzing of our own. In case you haven’t heard of meta-analyses before, a meta-analysis is basically just when you add the results of a bunch of different studies together in order to get a result that has greater statistical power. Considering that most randomized trials in health and medicine are too small to detect differences even if they do exist, this is often a necessary step in order to figure out if a treatment works or not.
Let’s look first at what happens if we remove the two studies that gave very high doses of hydroxychloroquine (which unfortunately means removing the vast majority of participants from the analysis). I’m also not going to bother to include the study (Tang et al.) that gave hydroxychloroquine 16 days after symptom onset (seriously, what were they thinking?). That leaves six studies. Here’s what we get when we meta-analyze them:
Unfortunately, there is still no signal of benefit. 2% of patients died in the group treated with hydroxychloroquine, and 1,7% died in the control group. The marginal difference seen is nowhere near statistically significant, and there is still not even a hint that hydroxychloroquine might be beneficial.
But of course, deaths aren’t the only thing that matter. If people can be kept out of hospital, or prevented from developing severe disease that requires invasive ventilation, that is also a win.
Only one of the studies (Cavalcanti et al.) looked at the ability of hydroxychloroquine to keep people from requiring invasive ventilation. In the hydroxychloroquine group, 7,5% required invasive ventilation, compared with 6,9% in the control group. This marginal difference was again nowhere near statistically significant.
So there is no signal that you get better results if you give more moderate doses of hydroxychloroquine. Let’s see what happens to mortality if we just look at the two studies (Skipper et al. and Mitja et al.) that gave hydroxychloroquine within three days of symptom onset. In these two studies, one person died in the hydroxychloroquine group, and one person died in the control group. Unfortunately, the total number of participants was only 700, which simply isn’t enough to tell if hydroxychloroquine given early has any effect on mortality, for the simple reason that the vast majority of people who get covid don’t become sick enough to die, regardless of what is done with them.
These two studies did however also look at the ability of hydroxychloroquine to keep people out of the hospital. Here’s what happens if we do a meta-analysis of hospitalizations instead:
Both studies appear to show a reduction in the number of people who go on to require hospitalization, and the reduction is actually quite big, with a relative risk reduction of 38%. However, the reduction is not statistically significant.
Of course, that doesn’t mean the reduction isn’t real. If you see a big difference between groups that isn’t statistically significant, that usually means the data set is too small. As mentioned, the data set here is only around 700 people, which is why even a huge 38% reduction in hospitalizations is not statistically significant. So this data suggests that there is a beneficial effect of hydroxychloroquine when given within three days of symptom onset, but more data is required before any conclusions can be drawn.
So, what can we say so far?
The evidence that exists from the randomized trials that had been published up to September doesn’t suggest any benefit from hydroxychloroquine when given at one week after the beginning of symptoms or later in the disease course. We can be pretty confident of this conclusion, since it remains even if we take away the two studies that used very high doses of hydroxychloroquine, and there isn’t even a signal of benefit in any of the trials. This means that hydroxychloroquine doesn’t have any role to play in the hospital, since people usually aren’t sick enough to require hospitalization until they’ve been symptomatic for at least a week.
There is a suggestion from from the two studies that did look at giving hydroxychloroquine early in the disease course that it might significantly decrease the risk of requiring hospitalization. A much larger trial would need to be carried out to see whether that signal is real or not.
So, has any new evidence appeared since September that might change or strengthen these conclusions?
Yes, there have been a few new trials produced since then, which we can use to update our meta-analysis. There’s a French study by Dubée et al. that gave hydroxychloroquine to high risk groups, with the start of treatment on average five days after the beginning of symptoms. This study actually showed a 46% reduction in the relative risk of death in the hydroxychloroquine group, but the study only had 250 participants and 17 deaths overall, so as with most of the earlier studies, this one was too small to produce a statistically significant result, even if one did exist. The result could easily be due to chance.
There’s a Mexican study by Cardenas et al. that gave hydroxychloroquine on average ten days after the beginning of symptoms, with a total of 214 participants. This study showed a marginal 7% reduction in relative risk of death in the hydroxychlororquine group, but again, the reduction wasn’t anywhere close to being statistically significant, and in terms of absolute numbers, there were 40 deaths in the hydroxychlororquine group and 44 in the placebo group, a difference that is so small that it could easily due to chance. The fact that 84 out of 214 participants in the study died is shockingly high, and makes me wonder a bit what they’re doing to their patients in Mexican hospitals. I guess they were only recruiting the very sickest patients in to the study.
There’s a study carried out in the United States by Self et al. that gave hydroxychloroquine an average of 5 days after symptom onset, and that included 479 patients. 25 patients died in the hydroxychloroquine group, and 25 patients died in the placebo group. This was a big, high quality trial, and the hydroxychloroquine was given relatively early, so the lack of even a hint of an effect on mortality is disappointing, and strongly suggests that even if hydroxychloroquine does have an effect on the risk of dying of covid, that effect is modest at best.
And finally there’s a study carried out in Qatar by Omrani et al. that gave hydroxychloroquine to young, otherwise healthy people with mild or asymptomatic disease (i.e. people without symptoms but who had a positive covid PCR test when they were screened). There were 152 people in the treatment group and 152 people in the control gorup. Not surprisingly, there were no deaths in either group. When it came to hospitalizations, there were three hospitalizations in the treatment group and four in the control group.
Here’s what we get when we add these studies to the meta-analysis:
What we see now is a marginal 7% reduction in the relative risk of death, that is nowhere close to being statistically significant. I therefore think it’s pretty safe to conclude that hydroxychloroquine is either completely ineffective when given on day 5 after symptom onset or later, or at best so marginally effective that it’s probably not worth bothering about. For comparison, remember that when we meta-analyzed the trials of ivermectin, there was an 87% reduction in relative risk of death that was highly statistically significant! Here’s the meta-analysis of ivermectin again, as a reminder of how impressive those results were:
Unfortunately, there haven’t been any new trials looking at hydroxychloroquine administered within the first three days after symptom onset, so we still don’t know whether it’s effective at preventing hospitalization when given that early or not. It’s a shame that question still hasn’t been answered, a full year in to the pandemic.
The study by Omrani et al. that I mentioned earlier was giving hydroxychloroquine early, but they never specify exactly how early, and a large portion of participants in that study weren’t actually sick, they were just asymptomatic carriers. But let’s add that study to our meta-analysis of hydroxychloroquine given within three days to prevent hospitalizations, just for fun. Here’s what that meta-analysis looks like:
Unfortunately, even with the addition of that trial, we’re still nowhere near statistical significance. To be fair, there is still a suggestion here that hydroxychloroquine, when given early, can decrease the risk of hospitalization. All three trials are pointing in the same direction. But even when added together, there is still not sufficient statistical power to say whether we are seeing real benefit or just random chance creating the appearance of benefit. What we would really need now is a big study, with at least a thousand participants, preferably two thousand, that were given hydroxychloroquine within three days of symptom onset. That would allow us to answer this question definitively.
Some people have argued that hydroxychloroquine only works when combined with azithromycin and/or zinc. Let’s examine that. The idea that hydroxychloroquine and azithromycin are effective when combined (and also that hydroxychloroquine is effective on it’s own, for that matter) is based on a tiny little French study (Gautret et al.) of very dubious quality that was conducted in early 2020, in which eight patients received hydroxychloroquine plus azithromycin, while 18 received standard care.
Personally I usually don’t even bother looking at studies this small because they’re far too small to yield any useful information, and really just waste everyone’s time. Anyway, what the researchers found was that the patients treated with hydroxychloroquine became negative on a covid PCR test more rapidly than the patients receiving standard care, while the patients getting hydroxychloroquine and azithromycin together became PCR negative a little faster still. From such small, questionable findings can big mountains of nonsense be built.
Since that study, three reasonably large studies looking at the combination of hydroxychloroquine and azithromycin have released their results (in fact, we’ve already talked about two of these studies a bit, because they also had a treatment arm that only received hydroxychloroquine).
The first (Cavalcanti et al.) gave 800 mg hydroxychloroquin per day and 500 mg azithromycin per day to 217 patients. These were compared with a control group consisting of 229 patients. Treatment started on average seven days after the beginning of symptoms. Five patients died in the intervention group and six patients died in the control group.
The second (Omrani et al.) gave 600 mg hydroxychloroquine per day and 500 mg azithromycin on day one, followed by 250 mg of azithromycin on the following days. There were 152 people in the intervention group and 152 people in the control group. As mentioned earlier, the study was only treating people with very mild covid, and unsurprisingly there were no deaths among the participants. Nor was there any difference in hospitalizations. Four people were hospitalized in the group receive hydroxychloroquine and azithromycin, and four people were hospitalized in the control group.
To be fair, this study was never statistically powered to look at hard end points. Instead it was powered to look at the probability of going from having a positive PCR test to a negative PCR test after six and 14 days from the beginning of treatment. So basically it was a higher quality version of the French study that started the whole hydroxychloroquine+azithromycin discussion.
Personally, I think this is a nonsensical endpoint because it is completely irrelevant to patients whether they still have a positive PCR test or not at a certain time point. But since this is what they were looking at, I’ll report what they found. At day six there was no difference between the groups. There was a trend towards decreased PCR positivity at 14 days among those treated with both hydroxychloroquine and azithromycin (30 people with a negative test in the intervention group vs 45 in the control group), but it wasn’t statistically significant.
Moving on. The third trial (Furtado et al.) was carried out in Brazil. It wasn’t comparing azythromin and hydroxychloroquine to placebo. Rather it was comparing the combination against just getting hydroxychloroquine. Treatment started on average eight days after symptom onset. Patients had to be quite sick to begin with to be included in the study. At the very least, they had to be getting 4 liters of oxygen, and half the patients were being invasively ventilated at the time they were included in the study. 214 patients received the combination therapy, while 183 just received just hydroxychloroquine. Overall, 42% of the patients in the combination therapy group died, compared with 40% in the group that only received hydroxychloroquine. In other words, there was no signal of benefit.
Based on these studies, I would say that there is no good evidence at this point that a combination therapy consisting of hydroxychloroquine and azithromycin has any role to play in the treatment of covid-19. Apart from hydroxychloroquine and azithromycin, there also has been a separate discussion about combining hydroxychloroquine with zinc. Is there any evidence to support this combination?
I have been able to identify exactly one completed randomized trial that has looked at combining hydroxychloroquine with zinc (Abd-El Salam et al.). 96 patients were treated with a combination therapy consisting of hydroxychloroquine (800 mg on day one, and thereafter 400 mg per day) and zinc (100 mg per day), while a control group consisting of 95 patients only received hydroxychloroquine.
The patients varied in how sick they were at the time point when they were included in the study, from only mildly ill to critically ill. No information is provided about the time point in the disease course at which patients started getting the treatment. Five patients died in the combination therapy group and five patients died in the hydroxychloroquine only group. There was no statistically significant difference in any of the outcomes studied.
Ok, this is just one relatively small trial. So the main thing we can conclude about the trial evidence on hydroxychloroquine combined with zinc is that it is extremely limited, really too limited to draw any firm conclusions. However, there is no signal of benefit in the one trial that has published results.
Two observational studies, both carried out in New York (Carlucci et al. and Derwan et al.), appear to show promising results in patients treated with a combination of hydroxychloroquine, zinc, and azithromycin. The first, involving 932 paitents, showed a 55% reduction in relative risk of death among those getting zinc in addition to hydroxychloroquine and azithromycin, as compared with those just getting hydroxychloroquine and azithromycin. The second, involving 518 patients, showed an 80% reduction in relative risk of death among those getting the full triple therapy, when compared with a reference sample that didn’t get any of the drugs.
That seems impressive. However, these are low quality observational studies that are seriously limited by the methodology used. The scope for confounding effects is huge. Therefore, these studies should be considered exploratory and hypothesis generating. They certainly should not be considered evidence of any cause and effect relationship.
Ok, let’s wrap this up. What can we conclude from all these studies?
The evidence that exists at the present point in time does not support the use of hydroxychloroquine as a treatment for covid. There is a signal that hydroxychloroquine could potentially decrease the risk of serious illness when given within three days of symptom onset, but there still isn’t enough trial data available to know whether that signal is real or not.
There is also a signal from observational studies that triple therapy consisting of hydroxychloroquine, zinc, and azithromycin is effective against covid, but no randomized trials have yet been done of the triple therapy that can corroborate that effect. The trials that have so far been published that looked at hydroxychloroquine in combination with azithromycin, and hydroxychloroquine in combination with zinc, have failed to show any benefit.
Doctor Rushworth first thank you for your work. I have to admit though that I’m really fed up with all this changing of opinions towards HCQ, which seemed (and I still believe so) that is a definitely useful treatment and also a cheap one (wonder why they went after it so much last year ?!). And even despite that the Lancet had to withdraw its publication after so many criticism and from that moment in there have been only favorable studies about it. So I honestly think (notwithstanding that “covid”, which has never been isolated by the way and it’s nothing more than a flu, let’s be honest about that, survival rate etc, you know better than me..notwithstanding that in almost the entire “infected” population does not even come with any symptom and thus requires no treatment) that this article is pretty much confusing to us normal people, and despite the very thorough analysis throughout it, reading that you still think is a non effective drug, so bypassing the big amount of studies that I’ve recently read that absolutely confirm its benefits (of course when it’s needed and in the correct stages) and debunk all the junk that has been told about HCQ.
I would like you to be more tended to highlight the positive outcomes of things in order to dismantle this rhetoric of hysteria and terror that the establishments wants to instill in people in order to keep their wicked plans for humanity going on.
Please, be brave, take truth’s and freedom’s side even more. Thank you for your work.
Best regards.
If you cherry pick your data sources, you can always get the conclusions you want, so that is exactly what I am trying not to do. I know a lot of my readers won’t be happy with my conclusions, but if I let what my readers want to hear guide my conclusions, then this blog really wouldn’t be about science any more.
It’s obvious that this was not what I meant nor my intention. I’m an objective and impartial person and so are you. However as I told you there has been lot of works I’ve noticed about the good effects of HCQ (which, I think you can agree, if administered in the correct stages and in the right way definitely outnumber the bad side effects) and mostly about those good effects even recently, that I didn’t notice you talked about a lot.
(https://articles.mercola.com/sites/articles/archive/2021/02/01/hydroxychloroquine-and-zinc-for-coronavirus.aspx
https://www.americasfrontlinedoctors.com/hydroxychloroquine/
https://www.amjmed.com/article/S0002-9343(20)30673-2/fulltext. Of course science is a continuous)
I know science is a continuous research field and thank God about that. But I just wonder how and why did you just focus more on some aspects that cause confusion and negativity in the reader about a mostly safe and cheap treatment (this we can all acknowledge, it’s not a new drug we’re talking about) instead of pieces (like the ones I found about) which show a totally (good) different story. Notwithstanding that I’m not even so concerned about HCQ this much, since “coronavirus” (like all the other tens of coronaviruses we’ve lived with throughout history) should be nothing to be concerned about more than an average seasonal flu.
But it was just to point out that even more than focusing on these, sometimes, wool issues matters we should focus on dismantling and debunking all the hysterical and fake rhetoric that has been maybe throughout last year on “coronavirus” so that people can understand the reality and live their lives normally and with freedom to decide about their own body.
Thank you again.
I’m french and have been following closely the work of Prof Didier Raoult in Marseille and his undeniable success with HCQ plus azithromicyne plus zinc.
India and African countries have used it with success because they had no other choices financially. If used along the lines of Raoult’s protocol, and in the early days, it’s been successful but politically at least in France, rejected because of pressure from big pharma who financially supported Macron’s access to power! The same applies to Ivermectin, another cheap and efficacious remedy which has been around for years. I trust Raoult as he’s a doctor and scientist and has integrity, with experience with HCQ which not many people on the covid scene have. His connection with Senegal and Africa is also of value in the use of this medecine
Cherry pick as you did in your arbitrary selection of HQC studies omitting the overwhelmingly positive results when HQC is introduced early WITH zinc and az*#th.
I haven’t cherry picked. I’ve gone through all the randomized trials. When you do something systematically, that is the opposite of cherry picking.
It’s not about so-called science – it’s always about cherry-picked science. Science is only science in text books.
Those RCTs, and the meta-analyses too, are filled with invisible error. School thoroughly programs one with unexamined assumptions. We believe (i.e. faith) that these studies are as close to truth as possible, but do not realize the extent of the problem – and because of the complexity, one can never know.
Specifically, RCTs can be jiggered by economics (by the funding source such as pharma), ideology, and are rife with cognitive biases. There is error, both intentional and not. Medical so-called science is not like easy physics with its finite set of variables and confounders. Biochemistry is a moving target. There are confounders one can never know about, and there can be millions of them, and they are not independent. Furthermore averages do not exist in reality, and people have extreme biochemical individuality. The optimal ranges for biochemical metrics are based on lab results from sick people. Medical so-called science never cures, it just treats with “managed care.” No MD or drug ever cured a single person. If they survived MD and drug intervention, they cured themselves.
Specifically RCTs have unavoidable distortions in experimental design, statistics, cohort selection, term of study, experimental dosage, the interpretation of data, and selection of end points. It’s easy to make it say whatever your cognitive biases and funding source wants to hear (that’s how you get follow-on funding). Due to the complexity, no one can figure out where it is wrong – one would have to be an OCD accountant. No one is motivated to dig comprehensively deep because it’s boring and there is no benefit to them for doing so, plus they’d just be ignored and probably shamed and disparaged for rocking the boat, so no up-side and lots of down-side.
RCTs are considered the gold standard by corporations and academics who most benefit by them, whereas anecdotal reports based on clinical experience are ignored. In theory RCTs sound good and they do have some utility wiping out the obvious confounders of the worthless correlation studies. That does not mean they are of ultimate value – it merely points to how worthless the observational studies are. RCTs only appear good in relative comparison, but you’re comparing dumb and dumber, not right and wrong.
Do not make the mistake of hanging your hat on them. They are not, as Wittgenstein said, “True enough.” Note that pharma can fund an RCT, and if it does not make their new multi-million dollar drug look good, they throw it out and start a new RCT with different parameters. No one, including MDs, knows what the prior RCTs concluded. Research form Harvard’s Safra Center found that 90% of new pharma drugs did next to nothing (except give Pharma big profit) – they provided maybe a 2% improvement (probably jiggered to pass the FDA rubber-stamp approval threshold (Pharma funds half the FDA’s budget and staffs it via the revolving door)).
We live in a post-truth world where we are programmed from every direction. It is not easy to think for yourself since we’ve been programmed from birth with unexamined assumptions. Science (including lots of anecdotal reports) is our only hope to do an end-run around our internal confirmation and availability bases as well as both the mainstream and alt-programming. You can’t really trust anyone and can’t trust RCTs either. It’s not easy moving onward through the fog and you have to be ready to backtrack so no ego allowed.
You have to do your own research and Hope for the Best. As Socrates pointed out, realizing your own ignorance (as well as that of others) is the beginning of wisdom.
“It Ain’t What You Don’t Know That Gets You Into Trouble. It’s What You Know for Sure That Just Ain’t So.” – Twain
““The first principle is that you must not fool yourself, and you are the easiest person to fool.” – Feynman
Good luck.
More to the point: garbage in, garbage out.
To paraphrase George Orwell,
He who controls the data going in, controls the conclusions coming out.
He who controls the controls coming out, ensures trillions in profits.
That is fair and what we need to do, have a broad good data with statistical power to prove a benefit or not. It would be good to have your opinion over the HCQ meta analysis from https://hcqmeta.com .
regards
Regi
Have you seen this with Peter McCullough MD?
He´s suggesting a little bit of other combinations. Do you know anything about them?
Hi Sebastian, this my be a cliché, but, english is not my first language, so apologies in advance for any gross or small errors; I´m from Brasil, and it´s quite a treat to read your post. They´re are really helping to make up my mind in these times. I´m here just to suggest for you to comment on the sweden situation; On worldometers.com they have 100% mild active cases. I´ve tried to find they´re guidelines but to no avail. Anyway, thx for your insights, cya
Yes, I agree with your reply pretty much.
To the doctor who performed the study review, were there ANY studies performed that took into account BOTH: 1. Administered early (3rd to 5th day of symptoms) AND 2. Administered with Zinc and Zithromax? BOTH parameters are required for those doctors who had success!!!
Good article.
I think most informed people know that it’s the triple therapy that needs to be studied. We’ve known the amounts to use from Dr Zelenko’s work but the drug companies/university cartels/WHO are making very certain that no high quality studies are being done of the triple combination. Then they can say HCQ is useless. It’s actually unbelievably evil, there is a therapy with great observational evidence but they won’t study it because it’s not profitable. It’s a sad state of affairs but the bottom line is science needs to serve people rather than corporate interests. And of course the media play their part too.
A primary pillar of an Emer Use Auth is no other treatment available…
S/he who has ears to hear, let them hear.
Ditto!!
You only look at people who take the Hydroxychloroquine after infection.
The largest study is Africa, with millions of people taking Hydroxychloroquine against malaria infection and very few cases of Covid.
Hydroxychloroquine works as a preventative for malaria and does the same for Covid !
That is again looking at observational data and saying it proves cause and effect. There could be a million different reasons why people in Africa are less likely to get severe covid, for example lower average age, lower rates of obesity, better levels of vitamin D, different weather. That’s why randomized trials are the only way to show a cause and effect relationship.
You are correct that I am only looking at hydroxychloroquine as treatment in this article. Now that we have effective vaccines, I no longer see much point in looking at hydroxychloroquine for prophylaxis.
I think the jury is still out on “effective vaccines”.
All the best
Steve
In Africa HCQ is a Sunday pill that people take as a prophylactic. It may be an observational report, but low COVID-19 rates in the population require science to extrapolate out the actions in the community to learn if an effective action is present. PCR tests are using way to many Cycles skewing numbers of “infected”. Science requires a search, not a coconspiracy among scientists to confirm an idea.
Vaccines!!! I think it would be wiser to treat people than inject the whole population with some experimental medical procedure with no long term safety studies and a totally new technology . I’m totally against it and will fight my damnest not to be a guinea pig! My body my choice, my health!
Citation ” … for example lower average age, lower rates of obesity, better levels of vitamin D, different weather.”
So the opposite is also true. The mortality by cause of death is associated with (Obesity, heart disease, cancer, age, etcw hat about ethnic groups, socio-economic classes.? ) .
Not because the use of hydroxycloroquine. Professeur Raoult Didier as a scientist investigate, as a doctor treats his patients and as a proffesor, he teaches. He is humble enough to say when it is the case ” I don’t know “. If the noble price is adressed to NOBLE people, Didier Raoult will be amoung them.
Thanks
I would be very curious if anybody has looked at the rather large population, perhaps in the millions, of people among us who take hydroxychloroquine daily for rheumatoid arthritis. How do their rates of covid, end of complications, compare with the average?
GREAT Point Steve!! I did not know about those stats in Africa – thank you for sharing that!!
Hi Sebastian,
What is your opinion on the analysis done at:
hcqmeta.com
and
c19study.com
They do seem to consider many more results then you did here and I cannot reconcile your findings with the outcomes there. There is indeed a lot of trial data. Moreover, although RCTs are superior, they are not the only form of useful data.
So in this case I am not convinced by your arguments and stick to the hcqmeta analysis.
Their analysis is based on observational data and cherry picking of end points. I think there are enough randomized trials that the observational data can be disregarded.
They also discuss all the RTC’s in great detail, so I do not agree that they are basing everything on observatonal studies. They are also focussing on early treatment since they argue that that is the correct way to apply it.
The variety in study designs is enormous with HCQ and adds to the confusion and interperability of outcomes. In your article I also see a great number of applications and endpoints and that may be the reason for inclonclusive outcomes. You may call it cherry picking, but I see them (hcqmeta.com) addressing design flaws and accounting for them to draw a conclusion on what really works.
The, by now, infamous Lancet HCQ-study was incredibly fraudulent and rightfully retracted, but it is clear that , if certain parties would want to obscure the positive effect of some treatment, they can just create a lot of fog around it. I believe this happens a lot with non-patentable, or cheap, interventions.
Disappointing, I was hoping to see some positive results for the triple combination of drugs. However, as there still has not been a good trial using hydroxychloroquine + Zinc +azithromycin, it is still an open question.
What it does show, is that Covid is not really a dangerous disease/virus and most people recover no matter what…. More akin to the common cold or mild flu, which can kill unhealthy people with co-morbidities, but from which nearly everyone recovers.
Absolutely, the question is still open, and it’s a shame there hasn’t been a randomized trial yet looking at the triple therapy.
It is ridiculous to ask for an RCT in the midst of a battlefield.
All you need are thousands of anecdotes from clinical experience and a protocol that does no harm and is cheap. If you don’t want to go with Dr. Zelenko, go with the frontline critical care docs at flccc.net. Dr. Varon has a 99% success rate. Dr. Marik has a 94% success rate (Dr Marik has also written four critical care text books).
The global average success rate for C19 is 75%.
Of course, on top of that, there is sufficient evidence in 200 plus studies at c19study.com as well as this retrospective study:
https://www.sciencedirect.com/science/article/pii/S0924857920304258
One might also wonder why the poor countries’ deaths per million is about five times lower than that of the rich countries with their ultra-expensive pharma monopolized healthcare system. In the US that pharma system has done nothing about the fifty-year epidemic of chronic disease and nothing effective against this pandemic. Could it be because they’re ranked 27th in the world for outcomes? And because they put profit over people? The current pharma C19 treatment protocol costs about $40,000 versus the Zelenko protocol at $20. They also kill 440,000 people every year in the US with avoidable errors and another 100,000 with MD correctly prescribed drugs, every year. MD’s are very well programmed pharma sycophants with an average US income of $300,000. They are not paid to think outside the box.
The question is only open if you require RCT evidence a priori.
There is no RCT evidence against the triple therapy. There is sequential observational evidence in favor of the triple therapy. (Of course, sequential retrospective studies on the evidence pyramid are the next best thing to RCTs.)
Has the well been poisoned against HCQ? Of course–it is very difficult to find patients to enroll unless they are biased in favor of HCQ. Nobody who believes that the triple therapy works wants to take a chance on being in the alternative arm if they can get HCQ. And everyone can get it if they look in the US.
So the rational conclusion is to use the triple (or quadruple) therapy based on the best available evidence, which is sequential and non-sequential retrospective studies.
Academics who care about RCTs should try to enroll people. But they almost always want to use hospitals, which is too late unless you are extraordinarily careful. There was a RCT study at St. Francis Hospital which was stopped because they couldn’t recruit participants.
Exactly. Almost everyone needs no treatment at all and the very vast majority of people are asymptomatic: the only ones that might have some issues are very old people with more than one co-morbidity. It’s lethality rate is 0.2% come on people, this discussions about HCQ or Ivermectin are wool issues, we should first highlight this above mentioned issues and reestablish freedom in the world (which in countries like Israel is disappearing with this horrible vaccine-passports).
Let’s remember besides that we’re talking about a virus which was never isolated and from what we know is the flu virus itself (why did flu disappeared from the world, no one has an answer). Wake up people, thank God for people like dr.Rushworth who deepens our knowledge, but it’s a fight against slavery and misinformation too. Wake up!
I say “amen” to your comments.
I admire Dr. Rushworth’s courage (AZ article very enlightening, also bought your book). There is no time for big trials when the ship is sinking. Dearest doctors: the general public is confused and families are fighting because those members that refuse shot are not welcome or “crazy”. The pressure is intense.
Hi Sebastian, thank you for all your work and analysis. As mentioned above, HCQ works best in combination with zinc and a medicine like azithromycin in early treatment. Therefor, all over the world general practitioner are reporting great results. Too bad these are usually not considered as evidence since it s not randomised trial etc. But should it be considered as empirical evidence that treatment works?
Furthermore there s a meta analysis available through this website: https://hcqmeta.com/
You might find this interesting.
Very kind regards, keep up all your good work.
thats right :
take paracetamol and wait !
wait for the scientists to come up with something else (if they dare to do so ) !
wait for the health institutions to allow early treatment (once the disease is over ) !
wait for bill gates to pay for a randomized HCQ study (and kill it ) !
wait for the virus to replicate in your lung and kill you !
According to Trialsitenews, Bill and Melinda Gates Foundation will fund an Ivermectin study…
to finance a study is a way to control it and make sure it will not interfere with the sacred vaccine carnival.
How about the Cuban Interferon medicin? Any studies?
It does look like hydroxychloquine certainly doesn’t aid recovery from Covid19 from your close analysis of rather poor data.
On a different tack, I wonder what your feelings are about patients who have had the virus being given a dose of a vaccine when they have recovered. So far, I’ve heard of three people being given a dose like this, so would it boost their immunity significantly?
Just as a piece of anecdotical evidence: When I got covid symptoms in March, just a very mild cold and a mild cough but with an odd pressure in my lungs, I immediately started taking chloroquine diphosphate, klorokinfosfat in Swedish, 250 mg per day. (I’d got some pills from a friend who had been travelling…) Since before I’d been taking Zink and other supplements (C, D et c), and of course I continued taking them. Already on the next day I noticed that the pressure in lungs was reduced, and on the third day the increased pressure was almost gone. On the fifth day I felt like normal, besides feeling somewhat weak.
Taken very early and together with zink, chloroquine diphosphate and HCQ seem effective. Already in March 2020 for example MEDCRAM posted covid videos about HCQ and zink as ionophore, but of course a zink was ignored in a number of studies since the plan was to make HCQ appear to be either without effect or dangerous (too high doses, for very sick patients).
As it has to be taken very early to have an effect if any. And the possibility for early treatment is small, because people do not search help until they need. It seem no point in further investigating.
there is no point in taking a treatment if you are sick !
no point in seeing a doctor !
just let things happen , be a stoician !
if you father is sick, tell him not to worry !
That is a good point. Even if you order a PCR-test on the first day of symptoms, the odds of having an answer within three days is low in most places. And even at the peak of the pandemic, covid was only causing 10-20% of respiratory infections, so probably wouldn’t make sense to give hydroxychloroquine to everyone with a respiratory infection.
If your choice is 4% high risk patient deaths v 0.1 % high risk patient deaths, why wouldn’t you treat URTIs assuming they were covid? Short term HCQ treatment is marvelously safe for almost everyone.
With 20% false negatives at best, is there any reason to discontinue treatment if you get a negative PCR result?
There are other coronaviruses besides covid which should respond to triple therapy.
That is a good point. I wonder whether there is enough hydroxychloroquine in the world to give it to everyone with an upper respiratory infection. I think if that became policy, production would need to be ramped up enormously.
Isn’t production of HCQ ramped up already? Will an occasional five day treatment of high risk people (40+ y.o.) impact supply heavily?
We in my family got a URTI in Oct. and treated with elderberry concentrate–an old folk remedy which contains quercetin–and zinc. My wife had to get it from either my daughter or me. The baby doesn’t go to day care and never showed any symptoms and was heavily exposed. My daughter is a surgeon and her symptom was fatigue. Mine was a dry cough. My wife’s symptoms were gi-flu-like. She tested negative for covid, but it’s possible that it was a false negative.
In any case, symptoms cleared within 24 hours of taking the remedy. The baby’s immunity points towards covid.
Whatever it was, my wife had a second round after three weeks and the same treatment worked the second time and then no repeats.
So, maybe the solution is to have some elderberry concentrate on hand.
(I tend to be skeptical about folk remedies, but there’s research into quercetin being a zinc ionophore and its widespread adoption as a treatment for URTIs is some weak evidence that it may work for coronaviruses.)
Interesting, I do plan to write about zinc and respiratory infections soon. The problem, as I see it, is that respiratory infections overall are extremely common. The average person has two respiratory infections per year. I haven’t run the numbers, and am not sure how big the global stockpile of hydroxychloroquine is, but I could imagine that if everyone was given a five day course of hydroxychloroquine at the onset of every respiratory infection, that global supply would run short very quickly.
The global HCQ market is $2.4 billion, after doubling in 2020. We could limit its use to rheumatic diseases and high risk covid patients (50+ y.o.) for early outpatient treatment only. Younger people would have to get by on some other antiviral–maybe ivermectin or quercetin or EGCG.
Actually, it looks like the pandemic is done already–at least in the US–so all this talk is really for the purpose of establishing better ways of handling future pandemics.
Fauci was recommending vitamin D supplementation in northern climes in winter in an interview, but it never got official approval.
I don’t believe the studies. Too many observational studies comparing treated to non-treated groups (matched for as many variables as possible) show decreased hospitalization (and by implication) severity of disease.
Remdesiver (a RNA polymerase inhibitor) was heavily promoted (prior to any studies) as the treatment for COVID-19. The early studies showed a positive response. This was obtain by altering the endpoint of the study from reduction in death (no effect) to reduction in hospitalization (borderline statistical effect). Further studies showed remdesivir to be and expensive boondoggle. Why was this so disturbing: Remdesivir is made by Gilead. Gilead underwrites a huge portion of the NAID budget. Gilead saw remdesivir as a make or break moment for the company. Bias in these studies? An HCQ regimen costs about $50. A remdesiver treatment costs about $3500. Hmmmm.
The mechanism for HCQ, zinc and azithromycin is compelling: COVID-19 enters the cell via a combination of 2 mechanisms: It grabs hold of the cell via the glycocalyx; once it grabs hold, it fuses with the AEC2 receptor to gain entry into the cell. HCQ alters the glycocalyx and blocks the binding site. HCQ alters the AEC2 receptor so the virus can no longer and then fuse with the cell to gain entry. Once inside the cell, HCQ inhibits RNA polymerase but its effect becomes blunted.
Zinc directly inhibits RNA polymerase. So it helps. Zinc needs help to get inside the cell as a zinc is a heavily regulated metal. HCQ helps zinc to gain entry by opening the pores. (It’s not actually an ionophore). HCQ aids zinc in gaining entry.
Azithromycin is a well known broad spectrum antibiotic. It has another unique property: it induces interferon 1 in respiratory cells. COVID-19 turns off interferon 1 production. Azithromycin helps neutralize this property. It also blocks initiation of a gram negative septic state (necessary for the initiation of immune dysfunction and coagulopathy).
The issue of QT prolongation with HCQ and AZN has been blown out of proportion. Out of 10,000 near death patients treated only 1 showed sufficient evidence to indicate the HCQ/AZN combination as a possible contributory issue.
I don’t believe the literature. All studies have overt and covert hidden biases. Never in the history of the world has there been so much political and industry mobilization directed against a possible cure for a disease.
Dr Rushworth, I hope you study the above comment. As one who normally appreciates your critical views, I found your looking at HCQ on its own very disappointing. As you have pointed out there are many limitations in RCT trials but one of the most basic requirements is to understand the mechanism under trial. The cellular process requires an ionophore and without that the trial is pointless. Many therapies require the support of other mechanisms, and it is a shame and indictment of the medical research that this is not appreciated. If the trial doesn’t include Zn++, just ignore it or ask why it didn’t. The process is maybe even more important than the statistical analysis and consideration of confounders which you discuss so well.
I included the one trial that looked at hydroxychloroquine plus zinc. It didn’t show a benefit. I would love to see more trials of the combination, but at present none exist that I have been able to find. Considering the strong support among segments of the public for hydroxychloroquine + zinc (+ azithromycin) it should have been quite easy for Zelenko or some other medical professional with a strong interest in the combination to do a kickstarter to fund a trial looking at the combination. Considering that all these drugs are generic and cheap, a trial like that could have been done quite cheaply. It’s a shame that hasn’t happened.
Dr. Rushworth,
The St. Francis study of Zelenko’s triple therapy was started in April and discontinued because they couldn’t recruit participants.
Then there is the political angle that those docs who allow their patients to participate in those trials are threatened with being hauled up in front of state medical boards.
So, no, it isn’t easy to study the triple therapy now in RCTs.
A possible cure would not legally allow an emer use shot.
A good summary of the trials – but were they the right trials? The shenanigans over HCQ underline the absolute requirement for rheumatologists to be involved in the development of Covid treatments. As long ago as last April I pointed out the issues over HCQ; in rheumatoid arthritis it is a weak drug, and nowadays would be unlikely to be used alone; it will not work once the immune process is fully established; and high doses produce high side-effects. And what are you trying to do in coronavirus infection? Not kill the virus, but prevent the cytokine storm. Giving it in very sick Covid-19 patients who have already developed CSS it is utterly useless – but that is what most of the trials have done. It’s like giving it in rheumatoid once joint damage is visible on X-ray and expecting that damage to reverse! So whatever the trials say, we are still in the “not proven” category with HCQ
I refer readers to my blog (https://bamjiinrye.wordpress.com). Starting on 26th April, then 1st, 1th, 21st, 22nd, 28th May, 16th June, 7th and 12th July.
Is it possible that the virus could have become less responsive to hydroxycloroquine as new variants arise? Thank you for your very thorough analysis Sebastian, but I wonder why so many doctors in the US deluded themselves that it worked. I suppose many people were going to get better regardless of what treatment they got and maybe it helps people, even medical professionals, to feel less helpless in the face of a new virus, to have some treatment available. I must admit I get disappointed when any initially promising treatment fails to follow through.
It’s hard to see these studies as a simple exercise in extending the sum of human knowledge when any discussion of HCQ has been so viciously suppressed by the media. The moment I saw that my Facebook link to America’s Front Line Doctors’ video on successful HCQ/zinc treatment had been removed by the censor was deeply chilling. And this for a treatment that is cheap, available and at least will do no harm.
Given that, it’s imperative at least that the full funding source for all these studies is made clear.
Also should point out, from my thorough albeit amateur investigations, that there seem to have been very few, if any, claims that HCQ works as a successful treatment/prevention on its own.
This article and the comments left so far neatly illustrate the difference between science and faith. Dr Rushworth summarises all the available data, good or otherwise, and the conclusion is clear: HCQ has no proven benefit and should not be used outside of clinical trials. As Dr Rushworth points out, now that there are vaccines about, there seems little point in pursuing these treatments that are likely to be of minimal effect.
The number of comments that clearly reject this scientific conclusion of the evidence suggests to me that there is a constellation of beliefs (covid denial of various degrees, faith in unproven alternative treatments, anti-vax views , conspiracy theories about Bill Gates etc, ) that form what is essentially a cult. No amount of evidence will shift these strongly held beliefs.
I have to say I do agree with your conclusion, the level of negativity about the power of meta-analysis is rather surprising. Dr Rushworth has produced another very useful summary of the actual trial evidence, with just the right amount of detail to drill down into – thank you!
I have to say, your nasty rhetoric is worded very well and is chock full of logical fallacies. Well done!
I am surprised, Dr Rushworth, that you have more or less ignored the reason that zinc is important in combination with hydroxychloroquine (and Ivermectin, for that matter) because, as Pathcoin has pointed out in his/her comment, it is the combination that helps prevent viral replication – by helping zinc enter the cells.
Just using HCQ on its own in various trials will presumably be relying on the individual’s zinc status as to whether or not it has a beneficial effect – which, of course, is another confounding factor that doesn’t seem to be taken into account in any of the studies that don’t use additional zinc.
We are often told that most people have a zinc deficiency as a result of diet, either through eating nutritionally-deficient processed foods or from foods produced through industrial farming which, over the years, has depleted the soil of many essential minerals (and there are studies showing this.)
So it would be unsurprising for a trial based entirely on HCQ (in the absence of added zinc) to fail!
As far as I know, the addition of the antibiotic is merely as a precaution against any concomitant secondary infection? I may be wrong about that, but I think I heard or read that somewhere – so it isn’t directly addressing the Covid infection.
Hydroxychloroquine along with zinc sulphate and antibiotic azithromycin is the combo of choice.
Could you comment on the data found in c19study.com ?
They say on their site that it includes 214 trials, but that is incorrect. The vast majority of studies in their analysis are observational studies, not trials. And they are combining a bunch of different types of end points (cherry picked based on whichever happened to show the biggest effect) in to a single meta-analysis.
I have often found c19study useful, if only to alert me to new studies. (Their analysis and push to get more info from study authors has also been helpful.)
I am a RCT fundamentalist when it comes to treatment of chronic diseases, but not for novel acute infectious viral diseases where the mortality curve is steep. There’s too much learning to occur for a RCT to arrive in time in most cases…at risk groups…disease progression…pathology reports…transmission modes…so I’m afraid we are stuck with observational studies in the heat of things. When a proposed treatment is relatively safe and inexpensive, how can anyone justify withholding it when no better alternative presents?
I see problems coming with the mRNA vaxxes. They monopolize certain cellular resources to make covid antibodies, but that might not be in the best interest of people being jabbed. Immune-compromised people might be seriously at risk…people with cancer, zinc deficiency, vitamin D deficiency, etc.
ok thanx, that is clear.
So would it be possible to have a – non-cherry-picked – meta analysis of the observational studies ? I can imagine that the scientific accuracy would be possible given the high numbers ?
Dear Sebastien,
Thanks for your thoughtful review of the hydroxychloroquine story. This is the most objective analysis that I have seen on this subject. However, I must disagree with your conclusion.
Many of the pro-HCQ people are flat out nutcases that only cite extremely low quality non-controlled observation studies and most of the anti-HCQ people will only cite those same studies while dismissing the few potentially interesting ones. Franky, it’s hard to see through all of the hype.
One of the major appeals of this drug is its extremely long and well documented safety record. Very few drugs have been studied so extensively and under a such a wide range of circumstances. https://www.facebook.com/notes/691243434858129/ This is definitely not the impression that one getting one watches CNN or if one reads the NY Times.
When I first became interested in HCQ in May, it seemed to me that the drug had three potential uses, each of which would have required different types of clinical trials, HCQ as a treatment for critically ill hospitalized patients, HCQ as a treatment for early disease and HCQ as a preventative.
Subsequent trials have clearly eliminated the first two. However, I continue to believe that HCQ may have had enormous potential as a preventative. https://www.facebook.com/notes/971241790054179/
That is, HCQ could have potential use for people working in very high-risk environments such as hospitals or people living in the same house with Covid patients and nursing home patients. To prove this would have required large trials with about 20,000 participants because the large majority of contacts will never actually contract Covid. Unfortunately, because of all of the negative hype. such studies will never be conducted.
Ron Eliosoff MD
High risk environments? I have read many studies that show that health workers (doctors nurses, cashiers) are less prone to get sick than the general population. Here is one i found quickly.
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0241956
There have been a few valuable early treatment studies that showed benefit for HCQ…Derwand being particularly valuable and the Procter study, too. The HCQ trials have been mostly underpowered and/or poorly done.
If a treatment works as a preventative, how does it fail to work as early treatment? Do you discount the zinc ionophoric activity of HCQ where zinc is the antiviral?
Thank you Dr Rushworth. As Pathcoin and others have said, it’s important to consider the mechanisms. How do we expect particular drugs/combinations of drugs to work? Even if I don’t fully understand them as an educated person I appreciate the discussion. So many of our public health officials in the west are out of touch with day-to-day health practice and treat the general public with contempt. They seem to be looking for a magic (and expensive) bullet to cure every health problem. Too often the voices of experienced doctors who care about the welfare of their patients are dismissed. I know who I’d trust my life with (the latter).
You are a medical charm! For me the most important information came early from a doctor in New York who was using the triple therapy to great success. Why all the studies did not employ the triple is beyond me but I do imagine ivermectin is better…but even better is simple old baking soda. Here in Brazil was an official study nebulizing sodium bicarbonate into ICU patients with seriously compromized lungs….to great success….doctors have forgotten the viruses are pH sensitive….
https://drsircus.com/general/bicarbonate-proves-to-be-cheapest-fastest-safest-covid-treatment/
Of course it can be prevenitive….and best to take it starting at very first symptoms….silly to wait till one is dying in ICU. This news was so good that it was taken down by that terrorist organization known has Facebook!
This statement “Most of the trials gave 400 to 800 mg per day, which is a reasonable dose, and unlikely to cause problems. One trial gave 1400 mg on day one, which is quite high, followed by 600 mg per day.” ignores the fact that the WHO’s own consultant in 1979, H. Weniger, looked at 335 episodes of adult poisoning by chloroquine drugs. Weniger on page 5 notes that a single dose of 1.5-2 grams of chloroquine base “may be fatal.”
Thus, 800 mg per day is *not* a reasonable dose, but is a potentially *fatal* dosage. To be an honest evaluation of hydroxychloroquine requires only looking at studies that gave *under* 1500 mg daily dosages and less than 3500 mg total dosage as the effective recommended dosages by all doctors treating mild to hospitalized cases is less than 3200 mg total and all conform to being *under* the advised potentially lethal dosages. See these two pages for more information: https://anthraxvaccine.blogspot.com/2020/06/who-trial-using-potentially-fatal.html and a compilation of articles http://www.kathydopp.info/COVIDinfo/COVIDTreatments/PharmaVsHCQ
800 mg is less than 1500 mg.
There is evidence that ivermectin works though or not?
Furhermore, a meta-study in Israel found Pfizer vaccine increases deaths 40 times for the elder and 260 times for the young, compared to covid itself. Can you elaborate on this on a separate article?
https://childrenshealthdefense.org/defender/israel-pfizer-vaccine-killed-more-elderly-than-covid/
Your link was removed. Here’s another one…apologies for the formatting…
http://www.nakim.org/israel-forums/viewtopic.php?t=270812&s=The_uncovering_of_the_vaccination_data_in_Israel__reveals_a_frightening_picture
Thank you for another expose´.
Tick the box 😬
I did not see mention of the July Henry Ford study which found a substantial reduction in mortality in a study of 2,541 patients treated on hospital admission. See: https://www.henryford.com/news/2020/07/hydro-treatment-study
Because it isn’t a randomized trial, it’s an observational study.
Hello Doctor,
Thanks for all your work, even if you didn’t get the result some seem to want.
Can you answer a question for me, nothing to do with HCQ, don’t worry I won’t quote you on it.
Do we accumulate antibodies in our systems even from extinct, or at least dormant viruses? I’m specifically thinking of the 1918 so called Spanish Flu pandemic. I’d just like to be able to say to doubters that we still have ‘protection’ against the Spanish Flu even though we are unlikely to ever encounter it again. Or if it is still out there in the environment unlikely to get sick or die from it.
Viruses are constantly evolving. In general, new viruses are most deadly when they first cross the species barrier, and then they usually evolve to become less deadly but more transmissible, because that makes them more effective at reproducing. I haven’t looked in to Spanish flu specifically, but my guess would be that a less deadly descendant of it is still circulating.
My understanding is that HCQ was first considered as a treatment for Covid because it was observed that people taking HCQ for other reasons did not get Covid. It is also known that one in vitro effect of HCQ is to assist zinc in crossing the cell wall to enter cells, and that zinc inside cells aids immune response.. Given those facts, one might reasonably expect that HCQ will be most useful if given before or immediately upon exposure, in people with adequate dietary zinc or zinc supplements. But your “gold standard medical tests” are never going to prove that, so it must not be true, right? Or maybe your idea of a “gold standard” is based upon a theoretical approach that amounts to looking for your keys where the light is best, rather than where you actually dropped them.
It doesn’t matter how good a hypothesis is for why something works, if the evidence shows it doesn’t work.
And what I say in the article is that hydroxychloroquine might work if given within three days of symptom onset or when used as part of triple therapy, but there isn’t enough data yet to say for certain either way. It definitely doesn’t work if given alone later in the disease course, that has now been shown beyond any reasonable doubt.
Thanks for your comprehensive analysis.
I’m wondering what your thoughts are regarding the large study from Henry Ford hospital published in August showing a large benefit of HCQ in hospitalized patients. Clearly there was a confounding problem of difference in treatment between the two groups overall, in particular corticosteroids. However I’m wondering how you would explain the significant benefit still found in 190 patients treated with HCQ matched with 190 patients not treated with HCQ who had the exact same propensity score, including steroid treatment.
It’s a retrospective analysis of observational data. There could be all kinds of different selection biases and other confounders hiding under the surface. We are talking about an observational study with 400 patients, there are a number of equally large or significantly larger randomized trials that fail to show benefit in hospitalized patients.
Your points are well taken
However I believe the study contained something like 2600 patients.
But I’m still puzzled as to why this study was such an outlier. The main criticism of the results of this study is that the HCQ group considerably more often received treatment with corticosteroids and also toxilizumab. The reason for this is presumably because the group that received these treatments were considerably sicker with a very significantly higher proportion of a quite extensive list of known factors and comorbidities that worsen prognosis. At the very least the study is a strong endorsement of these treatments.
However, although unaccounted for factors may have been present to explain the results, nevertheless in the group I mentioned in which there was a subanalysis, all of the known important factors that influence morbidity were identical, including both groups receiving the same drug treatments other than HCQ. It’s hard to imagine what other factors may have been influential considering the list of factors that were considered.
Not really arguing as much as I’ve always been considerably puzzled about this study’s results.
Here’s one possible explanation, just off the top of my head: people in the hydroxychloroquine had a stronger will to live. They were therefore more likely to request hydroxychloroquine because they’ve heard it might help. They also mobilized themselves more. Thus the beneficial effect would be due to increased motivation to survive and more mobilization, not hydroxychloroquine.
That’s just one possible confounder that’s largely impossible to correct for, there could easily be others.
thank you so much for your very comprehensive studies!!
Hanna
https://www.mediterranee-infection.com/wp-content/uploads/2020/04/Abstract_Raoult_EarlyTrtCovid19_09042020_vD1v.pdf
RE: “Two observational studies, both carried out in New York (Carlucci et al. and Derwan et al.), appear to show promising results in patients treated with a combination of hydroxychloroquine, zinc, and azithromycin. The first, involving 932 paitents, showed a 55% reduction in relative risk of death among those getting zinc in addition to hydroxychloroquine and azithromycin, as compared with those just getting hydroxychloroquine and azithromycin. The second, involving 518 patients, showed an 80% reduction in relative risk of death among those getting the full triple therapy, when compared with a reference sample that didn’t get any of the drugs.
That seems impressive. However, these are low quality observational studies that are seriously limited by the methodology used. ”
Above is linked one of Didier Raoult’s early studies. He is a well-known epidemiologist. Covid became highly politicized so everything to do with a simple therapeutic is subject to all the deceptive slings and arrows to which anything in the political arena is subject.
I read early on that HCQ must be taken with zinc to be reliably effective since the drug triggers immune system processes at the cellular level which depend upon zinc to be effective (in preventing the virus from colonizing such cells and then reproducing). Seems reasonable. The Azythromycin is for the pneumonia / bacterial infection in the lung which happens after the viral infection has achieved lift-off, so this is for those presenting such more advanced symptoms.
HCQ has been taken as an anti-malarial prophylactic for decades and his not highly toxic unless taken in high doses for a long time. This is known now because of so many with lupus and rheumatoid arthritis who take higher doses than the 400mg per week recommended as an antimalarial prophylactic. To combat flu/viral infection, I believe it is recommended to take 2000 mg the first two days and then taper off to 400 mg a day for about 5 days thereafter.
In any case, I think if you are going to review HCQ whilst lamenting the dearth of decent studies, why didn’t you start with the study by a reputable epidemiologist? Yes, it’s not a proper trial because he was treating actual patients with the infection, but it is still highly valuable and relevant. Most of the post-April studes were conducted in a highly politicized environment, many of them deliberately mis-using the medicines or obfuscating clear processes. Better to look at studies from before this covid global lockdown psyop began.
99 percent of real medecine is based on observational knowledge.
As a medical writer with 30 years of experience participating in and writing up the results of clinical trials, I suggest you look at the use of hydroxychoroquine to treat SARS-COV-1, which shares about 85% of its DNA with SARS-COV-2 and blew through before diseases were politicized and studies funded by Fauci and Gates were being used for (dis?)information purposes. It was pretty effective in those studies and was shown to have a prophylactic effect and could possibly inhibit the spread of coronavirus.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1232869/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7092815/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4136071/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5461643/
Another study showed that chloroquine is an effective anti-viral for a number of viruses. Also, “the suppressing effect is observed when the cells are treated with chloroquine either before or after exposure to the virus, suggesting both prophylactic and therapeutic advantage.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5461643/
Furthermore, with regard to mortality, what is the relative risk, in exact numbers? If HCQ yields a 9% greater relative risk of mortality, we need to know what that means in real terms. (I will check the studies later, when I have more time.) Because if the relative risk is only 1%, then a 9% greater relative risk of mortality is just 1.09%. If the relative risk is 10%, then a 9% increase is 10.9%. Not a lot of difference in reality. Thus, 9% sounds like a lot, but it might not be. And particularly given the quite stark differences in mortality risk for various age groups. CV19 is a discriminating killer, with mot of its victims over 60, and most of those over 70. The increase in risk is going to be extremely negligible for the majority of the population, and thus the benefit would far outweigh the risks in those under 60, if not in all patients.
I trust very little of this – the Cochrane study has my greatest trust; historically their science is solid and they don’t ascribe to the politically correct form of “science” so prevalent now in the US. No sooner did Trump tout HCQ as a treatment than the science establishment threw together that frankly stupid study giving HCQ to ventilator patients just to disprove what he said.
There is also a huge conflict of interest with Tony Fauci. He owns patents on the glycoprotein vaccine technology being used for this vaccine (as well as other vaccines). Here is a link to Fauci’s vaccine technology patents:
https://patents.justia.com/inventor/anthony-s-fauci
He’s making millions off of this vaccine and thus has a vested interest in first, scaring people and second, ensuring that all treatments are disproven, thus driving more business to his vaccines. Why is no one talking about this, or Fauci’s sketchy history with vaccines – for instance, the HIV vaccine, which actually gave people HIV.
There should also be widespread discussion about the treatment of patients with ventilators. CV19 does not produce pneumonia. It is more akin to an hypoxic injury, and we’ve know this for a year now. The hypoxia produces various toxic wastes in the lungs; ventilators destroy the lungs of patients by essentially turning those toxic particles into a sort of sand blaster via the high pressure used in ventilators. One study in NYC showed that 90% of patients on a ventilator died; it’s clearly not an effective treatment. Low-pressure oxygen is what is needed, and in most cases the lungs eventually clear themselves of the toxins, particularly if viral replication is halted via any of several means: vitamin C, zinc, or lysine, all of which have shown effectiveness, certainly anecdotally.
Hi Sebastian,
There are actually several RCT meta-analyses that found HCQ is effective in risk-stratified early outpatient treatment, e.g. https://www.medrxiv.org/content/10.1101/2020.09.30.20204693v1 . Regarding nursing homes, see also https://www.medrxiv.org/content/10.1101/2021.01.28.21250706v1
Most of the RCTs you’ve discussed are seriously flawed: late-treatment, lethal doses, no risk stratification, or underpowered. COVID remains mild in most people, and HCQ won’t work in late-stage disease. So what you need is risk-stratified early treatment trials. Many observational studies and a few RCTs did exactly this and found strong results.
It’s disappointing to see that even Sweden missed out on early treatment. Not just HCQ, but also other very simply means to minimize the risk of severe COVID in the elderly. It was completely ignored.
Cheers
I have seen the Meta-analysis by Ladapo et al, and am aquainted with the lead author. It is flawed because they have combined hospitalizations and deaths and positive PCR tests in to one meta-analysis even though these are completely different end points and therefore should not be meta-analyzed together. My meta-analysis is more methodologically correct, and also updated with more studies that have come out since they did their analysis. And it has excluded studies giving potentially toxic doses, so that is accounted for. I have also separated out studies giving hydroxychloroquine late, so that is also accounted for. And where the data is underpowered, as when it comes to treatment within three days, I have noted so explicitly and said that more data is needed.
The second article you reference is based on observational reports. I find it odd that people are criticizing randomized trials while citing observational studies. This is literally the same phenomenon we are seeing from the CDC when it comes to face masks – focusing on low quality observational evidence that says what you want and ignoring higher quality randomized trial evidence that doesn’t say what you want.
Thank you
Hi Sebastian,
You can absolutely combine different endpoints, many meta-analyses do this. The important point is the quality and context of the trials. The studies you’ve discussed weren’t sufficiently powered, risk-stratified early outpatient trials. So there were no meaningful results. The correct studies, whether RCT or observational, got good results. And it’s not surprsing: HCQ counteracts COVID progression on several levels (not just anti-viral).
Regarding observational studies, they are not a priori worse than RCTs, this is a common misunderstanding. They often include far more people than RCTs. Many drugs have been approved without RCT (https://bmjopen.bmj.com/content/6/6/e011666). And many RCTs are poorly done, or driven by commercial interests. The pandemic has shown this multiple times. And everything doctors have been doing during the pandemic was without RCT confirmation (even ventilating patients), or with false RCT confirmation (like remdesivir).
Real life is not as simple as you learn in med school 🙂
Cheers
As to combining end points, just because people do it doesn’t make it right. It is dishonest (whether intentionally or not) to combine a positive PCR test and death in the same meta-analysis – they are such utterly different end points in terms of seriousness that they should not be analyzed together.
As to observational studies not being inherently worse than RCT:s, I also disagree. Of course a giant observational study with 50,000 people is more likely to provide useful information than a small RCT with 50 people, but I would rather go with a well done RCT with 500 people than a well done observational study with 500 people every time. All else equal, RCT’s are inherently better. Observational studies always have confounders, no matter how hard you try to correct. There are practically an infinite number of health recommendations that have been made based on observational studies, that have later had to be retracted after it became clear that the effect was due to confounding.
Again, you can combine different endpoints, no problem. It’s actually a strength: it shows in different ways that a treatment works.
And no, RCTs are not “inherently better”, it’s a question of design. Remdesivir was a failure despite RCT results, and this is true for many other, often industry-funded RCTs. Regarding confounding, as mentioned in another comment, it is true for any single study (they all have weaknesses), but difficult to explain for many independent studies combined. So you would have to explain how they all got it wrong.
Just considering a few RCTs is a typical rookie “straight from med school” mistake.
Cheers.
My article doesn’t consider a few RCT’s. It considers all RCT’s. Remdesivir was shown to not work because the RCT’s showed that it doesn’t work, not in spite of them. I guess we’ll have to disagree on combining endpoints, if you actually think a positive PCR test and death are equivalent then I guess I won’t be able to convince you otherwise. And lots of observational studies can all point in the same direction because they all have the same confounders pushing in the same direction. This has been seen many times in nutrition studies.
Hi Sebastian,
As I show in my comment below, the HCQ RCTs you consider “good” are in fact very poor, and most still found a positive signal, confirming the large observational studies.
Different endpoints are not the same, that is why combining them makes the result even stronger (for example, they show faster viral clearance and lower mortality).
And you would have to show what the “common confounder” in these 100+ positive HCQ studies is. The situation is VERY different from nutrition studies, which are much more complex. Very poor comparison.
Epidemiologists are constantly overreaching and making claims that cannot be made with their chosen methodology. This has for example resulted in the disastrous current official nutrition guidelines that have caused an epidemic of obesity and type 2 diabetes. All epidemiologists should be required to stand in front of a mirror before breakfast and repeat 100 times: correlation is not causation.
It is not up to me to show what the common confounder is. The problem isn’t the confounders you know and can measure, it’s the ones you don’t know and can’t measure. I can think of multiple possible confounders that could cause all the observational studies of hydroxychloroquine to show benefit, for example that the people receiving hydroxychloroquine were more motivated to survive. Since there was alot of media attention paid to hydroxychloroquine early in the pandemic based on mechanistic studies these people would have been more likely to ask for hydroxychloroquine, along with engaging in a whole host of other behaviours that might actually be increasing their chances of survival, like mobilizing themselves more or getting sufficient vitamin D.
I question how “early” any hospital trial can be unless covid patients are selected from an outpatient pool where symptoms began no more than four days previously and treatment is started immediately (at least within four days of symptom onset).
Once the community well is thought to have been poisoned, it’s difficult to get people to drink from it. HCQ was smeared early on based on poor hospital studies which everyone should have quickly realized were poor, but the media and medical “experts” were quick to push the poison-well smear of HCQ and lots of people were fooled (including medical people who should know better).
The key hypothesis to test is whether HCQ works if given within four days of symptom onset to high risk patients given adequate levels of zinc (older men and type 2 diabetics are typically deficient) and adequate levels of vitamin D (more of a problem for people with dark complexions who don’t spend much time outdoors, e.g., work indoors). So supplementation with zinc and vitamin D should be considered in any study. That means testing zinc and vitamin D levels unless we find an adequate supplementation regimen. Even a small group of high risk patients should be adequate for determining effectiveness of the proposed treatment. Of course, if the well has been poisoned, it might be difficult to recruit.
Should vitamin C supplementation also be considered? Maybe. I certainly do it.
re: hydroxychloroquine might work if given within three days of symptom onset, but there isn’t enough data yet to say for certain either way
When I went overland through Africa I didn’t take the anti-malarial prophylaxis recommented by MDs. A 1.5 year prophylaxis seemed too risky. Instead I had to treat plasmodium falciparum for 4 times. Lariam had the worst side-effects, hydrochloroquine or quinine were harmless. All worked.
If I got symptoms of covid and had access to cholorquine (or ivermectin) I would take right away. The risk are just too small.
Zinc is tricky. I tried to raise my bottom low serum-levels by taking in average 50 mg/d for already 12 years. Only when I experimented with 70 mg/d for a year I saw a bid raised serum-levels (and high end of normal in whole blood, meanwhile below normal again). I doubt it could be raised in emergency fast enough.
That’s it, risk is minimal, upside is huge. It’s a no-brainer.
Zinc absorption is poor in some people. Maybe you just cannot absorb more.
I assume that you know about phytic acid in grains reducing zinc (and other mineral) absorption.
I do. Though I eleminated grains due to carbohydrate intolerance, I still get enough phytates from healthy foods like nuts.
What is amazing to me is that a year after the first pandemic ever to effectively shut down the world, so few really good studies have been done, not just for hydroxychloroquine, zinc, and azithromycin, but for a host of other possible treatments. Unbelievable! Our national health institutions have really failed us, badly.
Its understandable that the pharma insustry and the many people working free lance for it all want to prevent people from using early treatments.
It s not so easy to understand why people like Dr Rushworth and other bright independant scientists would willingly contribute to depriving the sick ones of the mean to avoid hospitalization and death.
Could it be because the evidence does not support its use at present?
re: Could it be because the evidence does not support its use at present?
Its all about risk/benefits analysis of any treatment. Had a walking-disabilty from a 80% stenosis at my abdominal aortan bifurcation. MDs pushed a synthetic aorta prosthesis. Had to google risks myself, since cardiologist only knew of acute 1 in 100 surgeries risks. Up to 50% of synthetic prosthesis would already have to be replaced within 10 years!
So I choose orthomolecular (high dose nutrients) medicine and life-style changes instead, with absolutely no randomized trials evidence, but almost no risks either (if done responsibly). And had lasting remission from my walking-disabilty after 7 years!
So the risk of dying from covid with certain comorbities being very high, the risk of hydrochloroquine almost non-existant (at least for malaria-prophylaxis it’s given out like candies; even long-term), experimental emergency use for such safe medications should never be denied by MDs, if asked for.
The evidence absolutely supports its use. What you would have to explain is how so many independent observational studies/trials (100?) found good results. It’s not sufficient to criticize any single trial, they all have their respective weaknesses. It’s also not sufficient to cite a few poorly done RCTs. It’s the sheer amount of independent evidence. Cheers.
Dr. Rushworth,
Does HCQ triple therapy reduce hospitalizations significantly in the case of high risk patients?
Which studies have asked this question?
four studies…Derwand, Procter, Su, Heras…all showed significant benefit (65% to 85% reduction in hospitalization)…Derwand and Procter used data from consecutive patients
This is strong evidence and enough for a provisional use policy pending stronger data. (Shall we go on about the CDC mandating late treatment with HCQ provisionally and essentially prohibiting early treatment? And that the CDC removed its EU for HCQ based on a retracted study?)
Observational studies that ask the right question are better than RCTs that do not, n’est-ce pas?
I believe your HCQ analysis is wrong. Look here: c19study.com
C19 is easily cured if you treat it early with HCQ, Zinc, and Azithromycin. I believe Dr. Zelenko’s protocol and that of flccc.net (similar but different) have the highest success rate – close to 100%.
The key is not waiting for the positive C19 test return, which takes about five days – that’s too late.
You need to diagnose immediately (no smell, fatigue) and start HCQ and Zinc. HCQ transports the zinc into the cell where it interferes with an enzyme the virus needs for replication. Treatment costs about $20.
The pharmacokinetics of HCQ take about ten days to reach the lungs, so the sooner the better – most HCQ studies do not realize this fact. Note that taken daily (or just take Quercetin or EGCG – both almost as good as HCQ) it is prophylactic and ready to go to work as a zinc ionophore. Easy, pandemic over.
Download Dr. Zelenko’s protocol before they sanitize it, as they did your book. Anything that does not align with the mainstream’s unexamined assumptions is canceled, or called fake news, or a conspiracy theory. This is happening everywhere, including in the internet archive. It is a badge of courage. Unfortunately, they may next cancel your blog.
Dr. Zelenko interview:
https://www.youtube.com/watch?v=MhLD1P5nH30
His protocol:
https://docs.google.com/document/d/1i7C_6H1Yq0u8lrzmnzt5N1JHg-b5Hb0E3nLixedgwpQ/edit
Be sure to also check out Flccc.net. https://covid19criticalcare.com/
Here’s the peer-reviewed paper: https://www.sciencedirect.com/science/article/pii/S0924857920304258
Thank you Sebastian. We appreciate your energy, information and analysis. How is it that a relatively new and unknown Doctor is doing it better than anyone else? What is it in your background that gives you this advantage over so many others?
I tested positive for Covid four days after my first symptoms of losing my sense of taste and smell. I had fever the night before I tested positive. I started Hydrochloriquine and a zpak the day I tested positive. I had no more fever and only other symptom was diarrhea for 3 days. I had been taking Vitamin C, D3 and Zinc for the last 6 months, faithfully, every day. I have no idea if the Hydrochloriquine, zpak worked or if my immune system was boosted by the vitamins but whatever it was, I had a very light case of Covid. I’m 74 years old.
A cytokine storm associated with an attack of acute malaria often produces an inability of mitochondria to utilise available oxygen. This activity of these cytokines, plus their capacity to control the pathways through which oxygen supply to mitochondria are restricted often killing the patient. HCQ is used to control this cytokine storm, often with dramatic results. Since a cytokine storm similarly kills certain Covid patients, why would one not use it as a preferential drug when presented with the symptoms of such a storm. Meta-analysis and double blind studies are controlled and outcome based with no consideration of one-off use of drugs that are likely to help in an extreme case. Dexamethasone is certainly not theoretically indicated but has become a useful aid in the treatment of Covid cases. Many cases would not benefit from this steroid but why would one not use it, even as a one off treatment if a patient as critical?
I’ve read in studies that about 25% of covid deaths are from cytokine storm. Other causes of death look to be systemic organ failure (SOF), followed by neurological and pulmonary embolii.
Covid is primarily a coagulopathic disease. This explains the silent hypoxia and SOF and embolic deaths we see.
Interesting how the Covid quandary turns people into zelots.
As they say “de gustibus non est disputandum” (replacing tastes with beliefs).
Hi Sebastian,
I took a look at the few RCTs that you thought were good. Turns out, they are all useless:
1) Cavalcanti: Terrible trial, not early treatment, full of bias and errors, paper should have been retracted.
2) Abd-Elsalam: The authors themselves note the trial “wasn’t sufficiently powered for survival endpoint”. But study found significant recovery benefit 28 days.
3) Skipper: Changed endpoints during trial, young patients, but still 50% reduced hospitalization rate in HCQ group.
4) Mitjia: Again, reduced mortality in HCQ group, but not sig. due to small sample size and no risk-stratification. In nursing home subgroup, RR is 0.49.
5) Dubee: Small early terminated late-stage trial, still found reduced mortality signal
6) Cardenas: Same. Late stage, positive signal.
7) Self: Early terminated very late stage (65% on supplemental oxygen) RCT
8) Omrani: Young patients, no risk-stratification.
That’s it. You relied on just a few very poor RCTs, many of them still finding a positive signal, and ignored the more than 100 often large observational studies that found clear benefit in early, risk-stratified treatment.
It’s really simple: treat early, not late. Do risk stratification, as most people need no treatment anyway.
See c19study dot com for detailed discussion of the trials above.
Hear, hear
Excellent comment.
Skipper had inadequate analysis and, unsurprisingly, a dodgy conclusion.
Followup letters of Skipper fix the analysis and conclusion.
All studies except those of high risk groups with early treatment should be ignored.
Pro tip: by the time patients go to the hospital, the treatment isn’t early. Family practice clinicians would know this. Non-practicing academics, not so much.
In the previous comment, I was thinking of Boulware’s study, which is a companion to Skipper.
Both relied on shipping, which is problematic when delays occur. One has to question whether Skipper’s trial adequately tested the “early” hypothesis.
In any case, I’d like to have seen a trial where high risk 70+ y. o. patients were given HCQ within four days of symptom onset. A nursing home would be an excellent setting for a study like this. Several nursing homes could be included to provide adequate numbers.
Every study has flaws, that is true of all randomized trials, and it is also true of all observational studies. The advantage with randomized trials is that the flaws are easier to see and figure out. In observational studies the flaws are to a large extent hidden.
And again, observational studies can only show correlation, not causation. In order to accept a causative relationship from only observational studies, the effect has to be massive, several hundred percent at least, as with smoking and lung cancer. The effect size in the observational studies of hydroxychloroquine is not big enough to assume that it is real and not due to confounding.
As I wrote in the article, the data from the RCT’s suggests that there might be benefits to treatment given within three days of symptom onset, but the effect is not statistically significant. More data from randomized trials is needed to decide whether the effect is real or not.
I just showed that the few RCTs you relied on are useless to answer the real question. The effect found by prospective obs. studies for risk-stratified early treatment is consistent and quite large, about 30% to 70%. Of course, if you consider studies with young people who don’t need any treatment anyway, you won’t find any sig. effect. Ironically, some of these studies were done because it was believed COVID was much more severe than it actually is.
Your attempt to explain away the observational studies by invoking a “stronger will to survive” in the HCQ group is quite funny, to be honest. Regarding remdesivir, dubious RCTs showed an effect, top journals published it, top agencies believed it, but observational studies already showed it didn’t work. Later WHO confirmed it. But Sweden is still using it! :))
So the lesson here is: do not just blindly rely on RCTs because they told you so in med school. Rely on good studies.
I’m sick of your condescending tone, and your continuous use of suppression techniques as cover for poor arguments, so I’m done discussing this with you.
Dr. Rushworth,
“And again, observational studies can only show correlation, not causation. In order to accept a causative relationship from only observational studies, the effect has to be massive, several hundred percent at least, as with smoking and lung cancer. The effect size in the observational studies of hydroxychloroquine is not big enough to assume that it is real and not due to confounding.”
80% reduction in hospitalization is a 400% benefit over SOC. (I don’t see how you get to hundreds of percent effect size other than by changing perspective.)
“As I wrote in the article, the data from the RCT’s suggests that there might be benefits to treatment given within three days of symptom onset, but the effect is not statistically significant.”
Boulware’s conclusion of statistical insignificance was dodgy, as shown by three letters–one by Watanabe, one by Wiseman, and one by Luco. (I looked at Boulware’s data myself and reached the same conclusion before Watanabe’s letter was published. It ain’t rocket science.) But I would argue that Boulware’s study was fundamentally flawed because of the shipping delay which would have reduced benefit.
Wiseman: “However, our initial review (pursuant to this protocol, v1.1) of the publicly released PEP dataset revealed that, contrary to the study’s conclusion, this four-day period referred not to the time from exposure to treatment as we (and others) had understood, but to the time from exposure and enrollment, a difference of up to 3.5 days.” [raised eyebrow]
In the Skipper study, only one person died in the placebo group of 211 people. One person died in the treatment group of 212 people, but even if there had been zero deaths in the treatment group, the probability value from a two proportion z-test is over 15%. So no treatment of any kind could be validated as decreasing mortality at the 5% level in this study. The authors’ comments imply that a study should be done with an older or more at risk group.
From: Hydroxychloroquine in Nonhospitalized Adults With Early COVID-19 [Skipper et al. Boulware listed at end.]
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7384270
Ann Intern Med. 2020 Jul 16 : M20-4207.
Published online 2020 Jul 16. doi: 10.7326/M20-4207
PMCID: PMC7384270
PMID: 32673060
“Our population was relatively young with 77% of participants being aged 50 years or less, with few comorbid conditions; thus, our trial findings are most generalizable to such populations. It is possible that hydroxychloroquine is more effective in populations at higher risk for complications, such as older persons in long-term care facilities”
“In conclusion, finding effective therapies against COVID-19 remains critical. Effective treatment of early, outpatient COVID-19 could decrease hospitalizations and, ultimately, morbidity and mortality.
Hydroxychloroquine did not substantially reduce symptom severity or prevalence over time in nonhospitalized persons with early COVID-19.
This trial may not inform whether an effect would be observed in populations at higher risk for severe COVID-19. Further randomized controlled clinical trials are needed in early COVID-19.”
Liv Malov,
You have strong opinions of Sebastians conclusion. What is your background in medical research and practicing?
Best
I love the way you just step right out into the battle with your thorough statistical and medical analysis. I would love to see a piece on Ivermectin next. I think this epidemic proves that parts of virology, epidemiology, immunology are broken. And often I read important critical analysis that receive too little attention perhaps because it doesn’t meet the dominant narrative. Here is an excellent interview with epidemiologist Knut Wittkowski: https://youtu.be/H40njXeT8og. Thoroughly logical in analysis yet swimming against the current politically correct tides. In my mind, as soon as science saw the potential for this virus in GOF research:
https://www.nature.com/articles/nm.3985
https://web.archive.org/web/20200319184758/http://english.whiov.cas.cn/Research2016/Research_Progress2016/201712/t20171215_187953.html
Then the testing for working anti-virals should have started. Otherwise why build these SARS-CoV chimerics? I see no evidence of in-vitro testing or mice/simian testing of new or old anti-antivirals against these SARS-CoV chimerics? Perhaps I missed it? In the middle of the pandemic groups of desperate doctors and researchers are prescribing and using Hydroxyclr and Ivermectin and even attempting to fund RCT trials themselves. Yet we have assumed that large pharma ran acceptable RCT trials even though for some the vaccine trial data are not always transparent as they would like.
We can ask: Why was science not better prepared? Why were not testable anti-viral solutions ready to go and funding for large scale RCTs ready at the start? Why fund GOF research and create chimerics at all if not to have solutions for a predicted Pandemic?
Dr. Nass accuses Gates of financing a fake anti-HCQ study:
https://anthraxvaccine.blogspot.com/2021/03/bill-gates-u-washington-lackies-publish.html
Long-time Big Pharma critic Peter Goetzche (who was fired from the Cochrane Group for criticizing Merck’s HPV vaccine) accuses Big Pharma of now routinely ghost-writing research papers for scientists and faking the data!
https://www.nejm.org/doi/full/10.1056/nejmra1614394
” There will always be an argument for more research and for better data, but waiting for more data is often an implicit decision not to act or to act on the basis of past practice rather than best available evidence.
The goal must be actionable data — data that are sufficient for clinical and public health action that have been derived openly and objectively and that enable us to say, “Here’s what we recommend and why.””
Liv and everyone, remdesivir was developed at great expense but seems to be a drug without a disease to cure. At least it has proved ineffective on on everything Gilead has tried it on. BUT there is a very serious disease, FIP (Feline Infectious Peritonitis) which it does cure! Normally, FIP is a death sentence for affected cats because there is no treatment yet, but pet owners are buying remdesivir online out of China at great expense and curing their beloved pets. This black-market remdesivir comes from the plant in China where Gilead manufactures it. People are paying thousands of dollars to get the stuff on the black market and Gilead could market it to vets for FIP, but I guess they don’t think the profits would justify the huge investment they have in developing remdesivir. Instead they keep trying to convince the world that it works against covid….
Remdesevir was designed to be given by IV, which means in the hospital, practically speaking. Too late to do much good. What were the researchers thinking???
Thoughts on this article Seb?
https://www.conservativewoman.co.uk/the-hydroxychloroquine-saga/
Dear Dr. Have you seen the following study? As far as I’m aware the largest study with early treatment with low dose, no or very little confounders. More than 8000 patients. So far the best study I have come across. Granted, it is an observational one, however of high quality. https://www.sciencedirect.com/science/article/abs/pii/S0924857920303423
That’s an important study. Too bad they didn’t include zinc, which might have made the difference from the other arm even bigger.
Why zinc?
Covid mortality is raised in older men v older women. 50% of older men have a zinc deficiency. (It’s a prostate thing.)
Type 2 diabetics tend to have a zinc deficiency.
Zinc deficiency has been shown to be associated with incompetent immune systems.
Zinc has activity against covid viral replication.
the NIH speaks a language that requires the scientific certainty found in very large prospective randomized double-blind placebo-controlled studies. These are very expensive to conduct, and so are usually only done when justified by being very expensive treatments that are likely to produce very big profits.
In the NIH view, until such a study has been run, even if numerous well-done studies show very strong clinical benefit, their language is that there is “no proof” of efficacy.
So, while this strong (to the point of overly rigid) criterion creates a certainty for things they say do work, it also dramatically limits the availability of safe and research-proven treatments. This approach markedly favors very expensive and profitable treatments. When the NIH says something works, it likely does (???). But when they say there is “no proof” (by their definition), in real terms that is often a very misleading and, ironically, unscientific statement.
So countless effective, safe and low-cost treatments go unused — essentially because they are inexpensive.
There is certainly the possibility that motives of cupidity are at work as you outline. They may be more or less unconscious; people have a way of reasoning themselves into what best serves their interest while remaining sure that they are being perfectly objective. There is also the attitude, outlined by Hayek in his book “The Fatal Conceit,” particularly the section around page 60 entitled “A Litany of Errors,” that it is irrational to act on anything whose effects are not fully known. That is an error, because in life we have to act all the time on things whose effects are not fully known, and sometimes cannot be fully known.
Covid is a potentially fatal disease, and HCQ/Azithromycin/Zinc is a treatment that is promising and taking it is close to harmless. So for the government to discourage its use is grossly irresponsible and might well be leading to unnecessary illness and deaths. And when you add the possibility of corrupt motive (Big Pharma/Public Health Bureaucracy/Academic Medicine) the whole thing smells bad.
This is highlighted by the numerous HCQ studies that seemed deliberately designed to fail.
Hello,
Some RCTs are missing it seems.
For inpatients, there is also: Ader et al., Ulrich et al. and Gonsalez et al.
For outpatients, please take a look at: Johnston et al., Amaravadi et al.
Doing a quick MA for inpatients studies, excluding the supratherapeutic-dosage ones (RECOVERY regimen) like you did, I got OR=0.85, 95% CI 0.64-1.14 for mortality. Far from significant but maybe not in futility zone. By comparison, the mortality MA for dexamethasone (which I found at metaevidence.org) gives OR=0.85, 95% CI 0.77-0.94. For tocilizumab, I found a recent MA of RCTs reporting RR=0.89, 95% CI 0.82-0.96.
For outpatients, you MA for hospitalization is perhaps slightly overoptimistic because you did not count one non-hospitalized death in HCQ group, and you counted two non-covid hospitalizations in the control group. On the other hand, there was one extra hospitalization in the control group of the Mitja study.
I Agree that ivermectin looks much more promising though, as well as other drugs (e.g. fluvoxamine) for early treatment.
All the best
Thanks, that is useful!
Diego,
Cribbing from c19study?
Johnston was a late treatment trial. Poor execution. ” The median time between symptom onset and receipt of study medication was 5.9 days ” Based on Raoult’s research and false negatives reaching a nadir on day 3 post symptom onset, viral load peaks at 3 days and clears at 8 days, on average. So the study was of late treatment. smh. There were only 9 patients 70+ y.o. receiving HCQ. Underpowered. An observational nursing home study with 39 patients had more value.
Ader was another worthless very late stage treatment trial. Hospitalized patients with 95% on oxygen at baseline. “Participants: 583 COVID-19 inpatients requiring oxygen and/or ventilatory support”
The problems with these studies are mountains, not mole hills.
Nope, not cribbing anyone. And I just checked this c19study meta-analysis (which is completely flawed by the way), it contains the same small inaccuracies I was pointing out. It looks like they counted non covid hospitalizations in Skipper et al. For mitja they also took RR=0.75, which is what is presented in the mitja paper as “intention-to-treat” analysis (actual ITT is what the authors call “safety population”). In ITT you are supposed to count all patients assigned to a group, so the correct RR would be ~0.7. In mITT, it should be ~0.65, i.e. one event less per group.
Ader should be included in an inpatient MA because, well, it is an inpatient trial. Same for Johnston: outpatient trial with a hospitalization endpoint so it should be included in a hospitalization meta-analysis.
I really don’t care about the c19study meta analysis…haven’t even bothered to look at it because it doesn’t address the key question. However, that doesn’t affect their other work, which has benefit for me.
I agree that Ader should be viewed as inpatient. But I see inpatient antiviral studies as a distraction, whether RCTs or no. My mistake thinking it was an outpatient trial. Thanks for the correction.
Amaravadi was underpowered and was terminated early, so benefits at endpoints couldn’t be ascertained. In addition, 29% showed SOB, so whether treatment was early is in question. One was hospitalized day 0 (almost certainly not early). It’s unclear how many days elapsed between symptom onset and day 0 treatment. The study was done remotely. There is no discussion of shipping delays between ordering medication and delivery. Median age 53, so likely very few older high risk (80+ y.o.) people. I think the authors said 40-80 y.o, so maybe one high risk person. Less than 4 days between symptom onset and test results. Add in shipping delays. Robin Armstrong’s nursing home observational report on the triple therapy is more useful. One death out of 39 residents treated with almost all very high risk.
What is the key question to be answered for covid and the triple therapy?
“Does the triple therapy work when administered within 4 days of symptom onset for high risk patients?”
Here’s a compilation page for those interested – including ivermectin.
https://sites.google.com/site/onedemocraticstatesite/peter-myers-digest-ivermectin-and-hcg
Sebastian: cannot reply to a reply of yours about HCQ supply but
a) anectodally, here in Mexico immediately after Trump’s lockdown announcement it became very hard to get and much more expensive. I ended up ordering online and had to wait 3 months for supply from India (from a US-based company that couldn’t get any).
b) a month or so ago one of the only 2 factories in the world making some of the prerequisite ingredients for HCQ burned down (in Taiwan), so I suspect supplies will be tightening.
I follow your blog and like your approach which is based on science and science-based medicine. Fair enough. But covid is 80% a political event and only 20% a true medical event. Now that we are a year in, there is no question but that covid is in the same rough area as annual flu. To circumstantially bolster the point about politics:
1. Look at the case numbers in the US fall off precipitously after January 20th. Any guesses as to why?
2. How come nobody in the UK or US is getting flu this season? Any guess as to why?
3. How come zones with little or no lock downs demonstrate the same or better results infection/death-wise and yet many are still encouraged to keep businesses closed, stay at home, not be able to visit dying relatives or bury them and still wear masks even though there is NO evidence that they are truly effective? Any guess as to why?
Covid is a tactical weapon in a geopolitical information/asymmetric war. It is naive to ignore this aspect. And it is necessary for real doctors like yourself, whilst eschewing political/conjectural commentary, to bear this is mind because of course you want to give your patients the best possible care. Sometimes you have to make adjustments to published ‘official’ guidelines when clearly they are part of various disinformation campaigns. Some of these might simply be due to ordinary financial corruption, such as Big Pharma approaches being pushed through the medical supply chain, but sometimes more macro political elements are in play and we all, doctors and patients, need to be aware of them as much as possible given how much deceit is in the mix nowadays in the public domain.
The uncertainty about whether a “covid” case is really covid is huge. Why are the public health authorities reluctant to do any spot checking of their numbers with viral culturing, although that was recommended by Heneghan’s paper on PCR and viral culturing? This seems very strange and suspicious. I approached my county health dept. with this question and they just ignored it. It’s quite reasonable to attribute malicious motives to public health officials who stonewall and ignore reasonable questions and gaslight. My county health dept. refused to ask the companies they contracted with to provide PCR testing what cycle threshold values they were using.
I tell you, there needs to be an investigation of public health officials.
Hello Seb,
I can’t get a hold of Ivermectin from here in the UK. I can however get hold of Ivermectin for my dogs…
Would it be safe to take 6mg pills that would normally be given to animals?
Regards
Graham.
I wouldn’t recommend taking a prescription drug outside the supervision of a medical professional.
The problem with the Self study is the claim that the hospitalized patients had a median duration of symptoms of 5 days. Covid virus, on average, maximizes its patient load at 3 days and its coagulopathic damage likely begins at day one of symptom onset, but symptoms are typically mild the first week post symptom onset (no SOB). So I don’t understand how the hospitalized patients only had a median symptom duration (not average) of 5 days. 70% reported SOB and 65% were on supplemental oxygen on admittance, which is very surprising.
Maybe many of the patients were demented and from nursing homes and it was difficult to ascertain when symptom onset occurred. And maybe there was some deception or by the nursing home staff or patients in order to get HCQ treatment. If there’s SOB, there’s likely a fair amount of incompetence about when symptom onset occurred.
In any case, I have problems relying on the Self study based on what has been reported about covid disease progression.
I think that you likely have a better chance of getting patients started early on treatment in an outpatient setting and avoid some deception that you see in hospitalized settings. But outpatient settings have their own problems running trials, especially followup. I was impressed by the Derwand study’s ability to get 141 sequential outpatients with 100% followup and testing criteria met so early. Yeah, it was a retrospective, but it looks to be high quality–better than Self.
A good meta-analysis: “HCQ is effective for COVID-19 when used early: real-time meta analysis of 218 studies”
https://hcqmeta.com/
Thanks for covering this Dr Rushworth. Very interesting.
Question. Wasn’t the use of HCQ as a prophylactic one of the main arguments of the pro HCQ crowd? Why isn’t it examined in your article? Are there no studies?
follow the real science :
no vitamin, no zinc , no hcq, not even a glass of water as long as there is no large randomized trial to back it.
(by the way, staying home is not a proved protocol either : we are guilty whatever we do )
The main reason I didn’t cover it was because there is now an effective vaccine that can be used as prophylaxis by those who are worried about getting covid, so from my perspective there is no longer much of a role for hydroxychloroquine as prophylaxis.
Hydroxychloroquine has a long history from which to gather safety data, whereas vaccines have a shorter and less comfortable history, unless you are the liability free manufacturer.
those new vaccines are very dangerous, especially for elderly.
And with that thoroughly PC reply, I now unfollow your blog.
If it turned out HCQ was an effective preventative, what would make it inferior to a vaccine in that regard? As far as I can tell the vaccines are more expensive, harder to manufacture and distribute, and have less comprehensive safety profiles. Besides, many countries won’t be fully vaccinated for a long time, if at all. I should point out that I’m on the fence about HCQ – I have seen no compelling evidence either way.
There isn’t enough hydroxychloroquine in the world to give to everyone prophylactically, so you would have to select a sub-group that received hydroxychloroquine maybe twice a week indefinitely. With the vaccine, on the other hand, you can receive two doses and then be done with it, at least for several months. And the evidence for the vaccines as an effective prophylactic is much stronger than the evidence for hydroxychloroquine as a prophylactic.
I have some concerns about the safety profile of the vaccines in relation to the size of the benefit in groups who are at low risk of severe disease (i.e. healthy young-ish adults and children), mainly because I think there is still a lack of good long term safety data, but for those who are at higher risk of severe disease, the benefit from the vaccines clearly outweighs the risks.
Yes, treating everyone makes as little sense as vaccinating everyone, and I wasn’t suggesting population-wide prophylaxis. But your point that HCQ would have to be administered more regularly is a good one. I’d still be interested to know if it’s effective for prophylaxis though. Who knows, it may work against other viruses for which we have no vaccine. We didn’t know Ivermectin had antiviral properties until last year.
And the cost of the vaccines is many times what it would take to use HCQ prophylactically.
Ramping up HCQ production for prophylactic use would be extremely inexpensive compared to the cost of vaccines for the whole world.
Dr. Rushworth,
Did you know that many surgical devices have not been subjected to RCTs because of rarity of use (underpowerment problem)? (Heard this from a surgeon.)
How is it that the triple therapy was being advocated in March and the only RCT planned was abandoned for lack of recruitment? Why were there all these late treatment RCTs and fake-early-treatment RCTs pushed by the CDC and no early treatment RCTs?
Maybe clinicians and scientists should push back about the triple-therapy well having been poisoned. I hear from lots of doctors that they smell a rat.
You don’t have to be a physician to think that something is corrupt when you see many RCTs that seemed destined to fail; late initiation after disease well progressed, use of only HCQ, or only HCQ and Azithromycin (no zinc), excessive dosages, etc. Academic medicine researchers’ careers are dependent on funding from the big pharmaceutical companies; they have an incentive not to come up with anything that they know will be unwelcome to them (like effectiveness of a cheap generic therapy), and to come up with things that will be welcome. NIH funds research and gets royalties from companies. Public health officials/Pharmaceutical Executives/Academic medicine researchers all seem to be abjectly conformist to the monetary incentives.
It’s possible that the people doing the large hydroxychloroquine studies designed them to fail, to get rid of competition from a cheap, generic drug. But there is one problem with that argument. It was the same people who designed and ran the studies that showed that dexamethasone, another cheap generic drug, is quite effective against severe covid. Why are they anti-hydroxychloroquine but not anti-dexamethasone?
clearly because dexamethasone and similar steroid here already standard of care in most hospital,
so that oxford was only opening an open door instead of adding something to treatment.
(although the strong influence of oxford tended for doctors to REDUCE the dosage of steroid, causing more death ).
I don’t know about that. Here in Sweden, at least, cortisone was pretty much contra-indicated as a treatment for covid, until the trials started to show benefit, on the belief that it would interfere with the immune system’s ability to fight the infection. And Sweden usually sticks pretty close to international consensus when it comes to medical therapy.
It’s only the outpatient early treatment antivirals that are a threat to vaccine manufacturers. People won’t take a chance on getting severely ill if they have an alternative (vaccine or antiviral).
Dexamethasone was used to treat critically ill hospitalized patients.
Notice that it was only antivirals that were slammed. If someone has a choice between an expensive, barely tested vaccine and a cheap, safe antiviral with a long track record, is that a tough choice?
Dexamethasone is not an antiviral and doesn’t prevent hospitalization or disease progression from mild to moderate covid. Dexamethasone is no competitor to the vaccines. Antivirals are.
Notice that ivermectin is being slammed in the press. “FDA warns against using ivermectin to treat covid” “Ivermectin does not alleviate mild covid symptoms”
That is a good argument. I buy that. It will be very interesting to see what happens with ivermectin over the coming months. Even the people who are strongly pro-hydroxychloroquine must surely agree that the evidence in support of ivermectin is much stronger.
Kudos to you for granting a point.
People were able to slide early ivermectin treatment RCTs thru, probably because Fauci wasn’t prepared to combat it and didn’t see it as a threat. Oops.
Sure, RCTs are superior to sequential retrospectives in persuasive power, assuming both test the same question. But will docs enter a trial where half their patients get a placebo where significant mortality in the placebo group is a real possibility?
Where is the ivermectin RCT of high risk patients?
If you are testing a known treatment against an experimental treatment of diabetes, then an RCT is ethical. Testing HCQ against standard of care or placebo to treat high risk patients would be unethical for most docs. And if you didn’t believe that HCQ was effective, would you trial it? So RCTs of antivirals look unlikely unless you are testing two different antivirals against each other. Which itself looks unlikely for a novel, acute, infectious viral disease. So, it seems to me, generally speaking, that sequential retrospective studies are the best we can hope for early in a pandemic and that it’s ridiculous to demand RCTs before treating with a safe, inexpensive, possibly effective antiviral with along track record. Back in March my weight about the effectiveness of triple therapy was about 60% based on Zelenko’s reports. Now it’s around 95% after Zelenko (147 sequential treated, 4 hospitalized, 1 death), Procter (922, 320 treated, 1.9% hospitalized, 0.3% death), and partners Brian Tyson and George Fareed (5,000 treated with 0.04% death–both of whom were seen with very late stage covid).
Switching gears, slightly…
If I were a doc, I would use both ivermectin and the triple therapy…and I would also prescribe vitamin D if the season/latitude indicated it and zinc for patients likely to be zinc deficient. And vitamin C to supplement. I would be proactive and have my office call patients on my list to inform them to call me with any URTI symptoms ASAP and vitamin D supplementation if the season/latitude indicated it.
Dr. Rushworth,
Since I answered your question about dexamethasone, will you return to the original question about RCTs of HCQ having been designed to fail?
…now switching gears to analyzing analysis…
What I see a lot in “scientific” analysis is that people can’t distinguish mountains from molehills.
Some people will assert that a late antiviral treatment RCT has more weight than an early antiviral treatment prospective study. smh I would think it obvious that testing the key question is more important than whether confounders have been eliminated.
Absolutely. I can’t say whether they were designed to fail or not, since I don’t know enough about the study authors to be able to determine that. Studies often look like they are designed to fail after the fact, even though that was never the intention, due to cognitive errors, or a lack of knowledge, or a poor understanding of statistics. Personally, I would be surprised if most of the authors went in to the hydroxychloroquine studies with the intention of failing.
Like I say in my article, the RCT evidence suggests that early treatment with HCQ is effective at decreasing the risk of hospitalization, but the evidence is statistically underpowered. If some doctors choose to give modest doses of hydroxychloroquine based on this underpowered RCT data combined with the observational data, while waiting for better data to become available, I can’t say that they are doing anything wrong. I would love to see a reasonably large RCT of early treatment that could confirm the suggested benefit.
Dr. Rushworth,
Please show me in the literature where late treatment of acute infectious viral diseases with antivirals is to be preferred over early treatment.
The public health authorities in the anglophone world (especially the CDC) only studied late treatment with antivirals. They also discouraged early treatment of covid with antivirals.
Please this explain to me. Are the public health authorities really that incompetent? After all, Fauci recommended using chloroquine to treat SARS-COV-1. And the CDC in Jan. 2020 recommended treating high risk patients testing positive for influenza with antivirals. Funny how the CDC would recommend that for influenza and not for covid.
I understand the problem with Monday morning quarterbacking, but I was seeing this problem as long ago as June 2020 and have no medical background. Why haven’t the AMA and CDC backtracked on their opposition to early treatment with HCQ? Bear in mind that the CDC removed its EUA regarding late treatment with HCQ based on the retracted Lancet study. The AMA and CDC COULD have taken a neutral position on HCQ, but instead have chosen to oppose HCQ. And what about their positions on ivermectin?
Can you really support the incompetence hypothesis?
01-13-2020!
“CDC recommends early treatment with flu antivirals for high-risk patients”
https://www.aha.org/news/headline/2020-01-13-cdc-recommends-early-treatment-flu-antivirals-high-risk-patients
why flu and not covid?
doesn’t this look a little suspicious???
why was bright saying to only give HCQ to treat covid under carefully controlled (hospital, late) conditions???
Here is the link to the CDC advisory mentioned in the AHA article…
https://emergency.cdc.gov/han/han00425.asp
Dexamethasone and other steroids were therapies for hospitalized cases where a cytokine storm was feared. HCQ/Azithromycin/Zinc was a possible therapy to avoid getting sick enough to need hospitalization. It was a possible outright preventative, i.e., a cure, rather than something to alleviate expected damage from advanced disease. And if it was highly effective, there would be less pressure for government to fund development of a vaccine which promised enormous private profits of many billions of dollars a year.
And there was the President Trump factor; when he said this was a possible therapy, there was a reflexive negative reaction among the medical elites, who like other elites, are a fairly ideologically homogenous group many of whom take great pride in their expertise and think it sets them above lesser mortals and who are not noted for their epistemological humility. For people with that frame of mind, suggestions from outside their expert “tribe” run into the “not invented here” attitude.
So I believe there may have been not only possible motives of not wanting to carry out any study whose results if positive would be highly unwelcome for its financial implications, but a political motivation.
Regarding possible danger to the elderly from vaccine, I saw reports of some deaths in care homes. But I wonder whether this isn’t a case where extremely frail people are done in by a normal small reaction to the vaccine? The average life expectancy of the care home population in the US is reportedly about 5 months. With very frail people, it might be a difficult decision whether to give them vaccine, or leave them exposed to the risk of the disease, either of which might push them over the brink. I suspect the risk from the vaccine is usually less.
Interfering with the immune systeme is exactly what Is needed in the iflamatory phase of the disease ´ hospital aptly use steroids for that ´ and they dont need the recovery trial to tel them.
I agree, but before the Recovery trial, at least here in Sweden, the infectious disease doctors were telling us not to use cortisone…
Didn’t that change because of retrospective studies when the docs discovered that the timing of the use of anti-inflammatories was key?
Maybe there were RCTs somewhere?
This is the study I was thinking of from May 2020…
“The use of anti-inflammatory drugs in the treatment of people with severe coronavirus disease 2019 (COVID-19): The Perspectives of clinical immunologists from China”
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7102614/
“Finally, the time window of anti-inflammatory treatment is very important. According to reports and our observation, severe patients usually underwent abrupt deterioration in 1–2 weeks after onset, and prompt initiation of the anti-inflammatory therapy at this extremely short time window is likely to achieve a favorable treatment response.”?
And I am still not a doctor.
I would like to point out that nobody is questioning the assertion that the _timing_ of anti-inflammatories is critical for the anti-inflammatories to be effective. Nobody is requiring RCTs of this, but it is just accepted based on some isolated, unpublished reports. One wonders why this question is accepted on such weak evidence and the question of early treatment with HCQ isn’t accepted on much stronger evidence.
There is a great deal of information on ivermectin here:
https://covid19criticalcare.com/
According to doctors who have successfully treated patients with HCQ, combining it with zink is essential. Zinc prevents viral replication inside cells but is poorly absorbed. Zinc ionophores (zinc transport molecules) such as quercetin, epigallocatechin-gallate (EGCG), and hydroxychloroquine facilitate zinc uptake. I wonder why didn’t mention this?
Here is a real-time meta-analysis on currently 219 HCQ studies, involving 3,381 scientists and 187,579 patients.
https://hcqmeta.com/
theasdgamer is right on-the thesis of incompetence is far less persuasive than that the public health officials, in coordination (tacit or not) with pharmaceutical manufacturers and academic researchers were out to suppress a cheap therapy. Note how authorities jumped to withdraw the EUA immediately upon publication of the Lancet article. That article immediately provoked criticism because of highly suspicious numbers that did not coordinate with official numbers from other countries. It had to be withdrawn when the authors could not or would not produce the data base. So the Lancet did not fact check before publication. No other article would have been published without any verification of data.
Thucydides,
I suspect that doctors who assert corruption by public health authorities, Big Pharma, medical journals, the media, elected representatives, and others will encounter trouble in their profession.
Dr. Rushworth isn’t looking for trouble. He provides a platform where those of us with less to risk can make the arguments.
If you ask the question, “qui bono,” which is merely due diligence, you can find the answer.
Who benefits from smearing early treatment with hydroxychloroquine? I can think of a few.
1. Big Pharma, of course,
2. public health authorities at all levels who have gained influence and increased funding because of the panic, which would subside if people knew that there were safe, inexpensive, effective antivirals,
3. the US Congress, who passed pork barrel legislation supposedly justified because of the shutdowns in several states and
4. manufacturers of novel, expensive antivirals which would be pushed by compliant media.
“CDC recommends early treatment with flu antivirals for high-risk patients” Great catch by theasdgamer. Good question for Sen. Rand Paul to ask Dr. Fauci on his next appearance before the Senate Health, Education, Labor, and Pensions Committee.
There is long term safety data for HCQ, there is no safety data for these so called “vaccines”, nor data to support claims of “effectiveness”. There is information recording “vaccine” adverse effects, including a disease which it seems to have caused, named “coincidence”.
For the Covid vaccine to get an EUA (Emergency Use Authorization), (quoting): there must be no adequate, approved, and available alternative to the candidate product for diagnosing, preventing, or treating the disease or condition.
https://www.fda.gov/regulatory-information/search-fda-guidance-documents/emergency-use-authorization-medical-products-and-related-authorities#A1
(See III (B) (1) (d))
This is likely one of the reasons for the Big Pharma/Public Health/Academic Medicine “iron triangle” push to discredit therapies like HCQ/Azithromycin/Zinc, Ivermectin, et. al.
+1000
There is at least one public health department that has pushed against the anti-antiviral narrative–the public health department of the state of Utah. On their website hydroxychloroquine and zinc are part of the suggested treatment.
Totally coincidentally, the case fatality rate for Utah is the second lowest of any state at 0.55%. Alaska has a lower cfr, but it has over twice as many tests per million, which reduced its cfr drastically.
Utah is a prime tourist destination and its hospitality numbers only declined 8% in 2020…no lockdowns except for indoor events and restaurants for a brief period. No quarantine orders–even for travelers.
What is the cfr for the UK? 2.89%? And the tests per million for the UK is almost _double_ Utah’s 1.4M tests per million.
What is the cfr for Sweden? 1.48%? And Sweden has 0.8M tests per million v. Utah’s 1.4M tests per million. If we set tests per million equal for Sweden and Utah, Sweden has 50% more deaths per million cases than Utah. (1.48% x 0.8M v. 0.55% x 1.4M = 1.18 v. 0.77)
What could mess up the numbers? Different mean Ct’s for PCR between Sweden and Utah.
That dam PCR uncertainty messes with so many different things, including vaccine efficacy.
The WHO chose to test hydroxychloroquinine in the least-possible-helpful way. Optimal was known to be early treatment plus zinc and azithromycin and low doses of HCQ. They chose to treat late, without zinc/azithromycin, and to higher (potentially fatal) doses.
“The WHO could not have plausibly chosen a less optimal treatment protocol [than their SOLIDARITY and RECOVERY trials].”
https://roundingtheearth.substack.com/p/how-to-rig-research-the-who-edition-105
The HCQ + Zinc paper you cited (https://link.springer.com/article/10.1007%2Fs12011-020-02512-1) included hospitalized patients. Dr. Zelenko has stated many times that HCQ + zinc is to be used early on in the outpatient setting. The paper might have been salvaged if they had restricted to their ‘mild’ category of patients only. But they did not. Another NothingBurger.