Chloroquine and Hydroxychloroquine as treatments for Covid-19

It happens that in a past life I had an allergic reaction to chloroquine, after I took it for a bout of malaria. I was living in a village in PNG where malaria was endemic, so was on weekly prophylaxis, but still came down with malaria. The treatment was yet more chloroquine, which did end the bout. But then I took my usual weekly dose, which tipped me into the reaction: I broke out in hives all over, for which I took a strong antihistamine, but I also had hallucinations for a night or two. NOT an experience I ever wished to repeat!
The villagers were amused to see the red splotches on my light skin, and told me cheerfully that malaria medicine makes you itch, and recommended I sit in the river to make it feel better!
The hives took a while to go away completely, and extreme itching even longer. And the villagers were right — sitting with my feet in a bucket of water temporarily soothed the itchiness. :)
Dismayed that chloroquine is being promoted without adequate research, certainly I’d only take it again under careful medical supervision.
 
2kidswithME said:
Dismayed that chloroquine is being promoted without adequate research, certainly I’d only take it again under careful medical supervision.
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Adequate research has yet to be done, but my best guess is this drug, alone or in combination, is more likely to be used on severe infections, where the relative risk will be different from mild cases. The biggest issue though is what happens to survival rates, and what percentage get serious complications. That is why further research is required.
 
lycaena said:
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Further to this.

The substance so far failed in all antiviral therapies, but this didn’t prevent Raoult from deciding that chloroquine can cure corona virus infections, serious side effects notwithstanding. To prove that, Raoult treated 26 patients at his institution with the derivative hydroxychloroquine, alone and in combination with the antibiotic (meaning antibacterial!) drug azithromycine. The study was not randomised, ethically approved only after it already began, and it was not really controlled: the 16 control patients were treated in different clinics.
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https://forbetterscience.com/2020/0...r-raoult-to-save-the-world-from-covid-19/amp/
 
This is becoming a real problem in France. Everybody asks for chloroquine, people with lupus (who really need it) are afraid of shortages. They can't recruit people for the big well designed trial that could tell if it works or not, because nobody wants to be in the no-treatment harm...
Raoult is selling a book on epidemies (directly n°1 seller), hords of trolls are insulting people who dare say his trial is not conclusive on twitter.
And more to say, ut I'm too worn off to add more.
 
hinterland said:
Not an ignorant question at all. I don't know if chloroquine is structurally similar to quinolone drugs, but I think possibly yes. Chloroquine and hydroxychloroquine are 4-aminoquinolines, and 4- quinolone is a compound derived from quinoline.

I too have had a serious adverse reaction to fluoroquinolone drugs in the past that still affects me today, and ever since I've been more hypersensitive to any drugs or nutritional supplements that I put into my body. So I don't expect I'd tolerate chloroquine very well and be wary of it for myself.

Probably the most well know, and significant, potential long-term side effect of chloroquine drugs is retinopathy (causing loss of vision), they can also cause hearing problems in some people.

The range of potential side effects is listed here:
https://www.drugs.com/sfx/chloroquine-side-effects.html
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By the way, just want to add that hydroxychloroquine is a significantly less toxic drug than chloroquine, and so would seem to be a better treatment prospect, assuming comparable efficacy.
 
There is a bit of push back on hydroxychloroquine hype early in the recent TWiV podcast. Basically they are saying the study was not correctly controlled because patients decided if they wanted experimental treatment or not based on how they were feeling and HCQ needs to be properly trialled as the cohorts were very small, the treated cohort had more mortality than the untreated controls and so it does not provide conclusive evidence HCQ is helpful in a clinical setting.

http://www.microbe.tv/twiv/twiv-593/
 
Attached is a newly released randomized, blinded, placebo-controlled study of hydroxychloroquine in mildly sick, hospitalized Covid patients in China. Sample size is fairly small at 62.

One inclusion criteria was that oxygen saturation at baseline had to be above 93%. According to a physician interviewed on Vincent Racaniello's podcast last week, oxygen saturation of 92% or higher is a good prognostic indicator in Covid patients.

Patients in the treatment arm received 200mg of hydroxychloroquine twice daily for five days.

Relative to controls, time to resolution of fever and cough was about a day shorter in the treatment arm than the control arm, which is encouraging but not dramatic. Nobody in the treatment arm progressed to severe illness vs 13% in the control arm. CT scans between the day prior to study entry and day 6 improved in a higher proportion of treated patients than in controls.
 

Attachments

It looks like one trial from China says there is benefit, and the other one Andy posted says there isn’t any? Is it because it possibly only helps mild patients? Or that it works alone better, than it works in combination with the other drug? Or that the sample size for the Chinese trial was too small? Andy do you know the sizes of the severe trial you posted - is it bigger than that of the other trial?
 
The Q T Interval in Patients with SARS-CoV-2 Infection Treated with Hydroxychloroquine/Azithromycin (2020) Lenon

We report the change in the QT interval in 84 a dult pat ients with SARS-CoV-2 infection treat ed with Hy droxychloroquine/ Azithromy cin combi na tion. QTc prol onged maximal ly from baseline betw een days 3 and 4. in 30% of patients QTc increased by grea ter than 40ms. In 11% of pat ients Q Tc increased to >500 ms , repres enting high risk group for arrh ythmia. The developmen t of acute renal fai lure but not bas eline QTc w as a s trong predictor of extr eme Q Tc prolong ation.
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https://www.medrxiv.org/content/10.1101/2020.04.02.20047050v1.full.pdf
 
Pharma-Funded Group Tied to a Top Trump Donor Is Promoting Malaria Drug to the President

Founded by one of Trump's top donors, the Job Creators Network has been pushing Trump to approve the use of hydroxychloroquine for treating COVID-19.

A fight broke out among the White House coronavirus task force over the weekend regarding the potential use of anti-malarial drug hydroxychloroquine for COVID-19 patients.

According to a report from Axios, National Institute of Allergy and Infectious Diseases Director Dr. Anthony Fauci objected to task force members’ characterizations of the drug, saying that there was only anecdotal evidence of the drug’s effectiveness and cautioning that much more data is needed.

Fauci’s comments set off a heated exchange with Trump economic advisor Peter Navarro, who reportedly raised his voice and accused Fauci of being the only task force member who had objected to Trump’s China travel ban. It was the first such confrontation among the task force, according to Axios’ source.

Since late March, President Trump has repeatedly promoted the use of the drug, despite the limited testing that has been done on its effectiveness for treating COVID-19.
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https://readsludge.com/2020/04/06/p...r-is-promoting-malaria-drug-to-the-president/
 
minimus said:
The attached study was published a day or two ago by a group of French doctors on the use of hydroxychloroquine and azithromycin to treat hospitalized Covid-19 patients.

The study has a number of problems, most of which the authors acknowledge:
  • It was not placebo-controlled or double-blinded.
  • The sample size is quite small at 36.
  • Six out of 26 patients in the treatment arm were lost to follow-up, three because they had to be put into the ICU and one because they died.
  • The outcome measure -- the percent of patients who tested negative by nasopharyngeal PCR for SARS-Cov-2 six days after study entry -- may not correlate that well with a patient's clinical outcome. It is plausible that a patient could clinically deteriorate and die because of a cytokine storm or a secondary bacterial infection after they test negative for the coronavirus.
  • The authors do not explain that clearly why they chose this outcome measure, so it is possible it was cherry picked from a range of other measures (e.g. change in oxygen saturation, body temperature, or breaths per minute, etc.)
On the plus side, the PCR test is at least objective in nature, so maybe less prone to placebo effects and observer bias than a subjective outcome measure. In addition, the patients in the treatment arm were on average significantly older (51) and therefore presumably more prone to severe illness because of their age than controls, who were on average 37 years old.

The authors found that 70% (14/20) of the treated patients had a negative PCR test 6 days after study inclusion vs. 12.5% (2/16) for controls.

The authors also found that the combination of hydroxychloroquine and azithromycin appeared to be more effective in clearing the virus -- with 6 out of 6 patients testing negative by PCR on day 6.
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The type of balanced analysis contained in this thread is what we come to Science for ME for. Kudos to @minimus for critiquing this study before many many other people did. Here is one of the first critical reports that I saw on Twitter from Elizabeth Bik on March 21, two days after @minimus


Who then wrote this article on March 25
https://scienceintegritydigest.com/...zithromycin-treatment-of-covid-19-infections/
 
Seems like all bad scientists use the same bad methodology and then resort to intimidation and bullying to get through.
"Old wine in new bottle" might I say...

Dr. Didier Raoult: Bad science on COVID-19 and bullying critics

The COVID-19 pandemic has been a golden opportunity for quackery and conspiracy theories, such as the willful misinterpretation of a study in order to claim that the influenza vaccine makes people more susceptible to SARS-CoV-2, the virus responsible for COVID-19, or that 5G networks and glyphosate somehow make the infection more deadly. Pseudoscience like this is to be expected from cranks, of course; so it is no surprise that antivaxxers, anti-GMO cranks, and other conspiracy theorists are fusing their favorite pseudoscience and conspiracy theories with conspiracy theories about COVID-19 in order to create meta-conspiracy theories. Unfortunately, the COVID-19 pandemic has also revealed just how weak the allegiance to evidence- and science-based medicine is among physicians, who have embraced unproven treatments, in particular chloroquine and hydroxychloroquine, the latter sometimes with azithromycin. True, President Trump and his allies have been promoting the use of hydroxychloroquine with minimal evidence as the latest bright shiny object that let Trump’s magical thinking run wild with the hope that a magic bullet had been discovered to get us out of this crisis. However, before that it was Chinese and European physicians who had embraced the idea of using hydroxychloroquine to treat COVID-19, none more prominently than French brave maverick doctor Didier Raoult, who is now not reacting well to criticism at all. In fact, he just doxxed a French physician and critic and threatened to sue him, as you will see.
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https://respectfulinsolence.com/2020/04/14/didier-raoult-bad-science-bully/
 
I liked the "Brave maverick doctors are not all quacks, but all quacks are Brave Maverick Doctors." since it is a truer example of how numbers work than we get from the Brave Maverick Doctors treating ME.
 
This looks more and more like a debacle... (reminds me something on several accounts)

More deaths, no benefit from malaria drug in VA virus study

Researchers analyzed medical records of 368 male veterans hospitalized with confirmed coronavirus infection at Veterans Health Administration medical centers who died or were discharged by April 11.

About 28% who were given hydroxychloroquine plus usual care died, versus 11% of those getting routine care alone. About 22% of those getting the drug plus azithromycin died too, but the difference between that group and usual care was not considered large enough to rule out other factors that could have affected survival.

Hydroxychloroquine made no difference in the need for a breathing machine, either.
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https://apnews.com/a5077c7227b8eb8b0dc23423c0bbe2b2

(The methodology doesn't seem great tough, so may not tell us a lot in fact...)
 
No Hydroxychloroquine Benefit in Small, Randomized COVID-19 Trial
Marcia Frellick

April 16, 2020

"Hydroxychloroquine (HCQ) does not help clear the SARS-CoV-2 virus or relieve symptoms for COVID-19 patients more than standard care alone and has more side effects, a randomized controlled trial of 150 hospitalized adults in China suggests."

requires registration to view full article
https://www.medscape.com/viewarticle/928798?src=soc_tw_share
 
My dad sent me this video tonight. Hmmm?

It's not a video you really have to watch in it's entirety, he just goes over one by one a number of the Covid-19 Hydroxychloroquine studies that have come out and he critiques their methodologies. In addition he argues that the drug is not being given until patients are already in too severe of condition and that it isn't being given with zinc (is there evidence it should be?). He ultimately comes to the conclusion at the end that all the studies coming out are 'shoddy' and poses this against the supposed observation that the drug seems to be working in places such as France, Costa Rica, New York, etc.

The hydroxychloroquine saga has become quite the debate. Am I correct in thinking @Jonathan Edwards remain skeptical of it's use for Covid-19?


 
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