Hydroxychloroquine, Anthony Fauci and Kevin Drum
This is a comment on “Is Anthony Fauci Really Our Truthteller-in-Chief?” by Kevin Drum. I will briefly summarize. Drum quotes from the latest press conference
“Is there any evidence to suggest that, as with malaria, it might be used as a prophylaxis against COVID-19?
DR. FAUCI: No. The answer is no.”
Later after Trump says hydroxychloroquine is the cure for Covid 19 Fauci changed his line to
Q I would like Dr. Fauci, if you don’t mind, to follow up on what the President is saying. Should Americans have hope in this drug right now? . . .
DR. FAUCI: No, there really isn’t that much of a difference in many respects with what we’re saying. The President feels optimistic about something — his feeling about it. What I’m saying is that it might — it might be effective. I’m not saying that it isn’t. It might be effective. But as a scientist, as we’re getting it out there, we need to do it in a way as — while we are making it available for people who might want the hope that it might work, you’re also collecting data that will ultimately show that it is truly effective and safe under the conditions of COVID-19. So there really isn’t difference. It’s just a question of how one feels about it.
Drum thinks more highly of Fauci’s first answer than of his second answer. He guesses
“It’s obvious what he really thinks, after all: hydroxychloroquine is nonsense, period. ”
The problem is that Fauci’s first answer was simply incorrect, wrong, a false assertion on a matter of fact. I am sure he was not lying, but there absolutely 100% no doubt about it and no grounds for debate, there is “evidence to suggest that, as with malaria, it might be used as a prophylaxis against COVID-19?@
I link to the top general science journal
“Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro,” Jia Liu, Ruiyuan Cao, Mingyue Xu, Xi Wang, Huanyu Zhang, Hengrui Hu, Yufeng Li, Zhihong Hu, Wu Zhong & Manli Wang, Cell Discovery, 18 March 2020
That is not proof that it is effective in vivo. However, given the fact that side effects, interactions etc are very well understood, I think there is no excuse for not prescribing it absent the well known counter indications.
Asserting that it is clear that Fauci thinks Hydroxychloroquine for Covid 19 is nonsense, and that he should say so Drum and others risk convincing people not to use it and risk causing deaths.
Why do people assume that they understand the evidence ? I do because I have noted the pattern that when I disagree with doctors about patient care, they end up saying what I originally said (I promise you I am not the only person who perceives this pattern).
The rule that Trump is always wrong is as near to perfect as any rule of inference can be, but it is always best to double check. Say by googling [hydroxychloroquine inhibits Coronavirus ].
Also read angrybearblog
https://clinicaltrials.gov/ct2/show/NCT04261517?term=hydroxychloroquine&draw=2&rank=7
I say don’t wait for the results of this trial. Patients in the control group are among the few who I think should not get hydroxychloroquine
Are you aware that this is a very dangerous drug? Because your gungho lack of nuance is pretty loudly suggesting you don’t.
JDM:
Explain what you believe to be bad about it. I am pretty sure Robert already knows its dangers and that of chloroquine.
hydroxychloroquine is for a viral infection not a bacteria inflection which is why they use an antibiotic such as Azithromycin (ZPak to my knowwledge). “Azithromycin 5 Day Dose Pack is used to treat many different types of infections caused by bacteria, including infections of the lungs, sinus, throat, tonsils, skin, urinary tract, cervix, or genitals.” The Chinese even said the same. That is a flawed study unless it is to prove the Hydroxychloroquine does not work on bacteria infections.
I am familiar with known side effects and risks of hydroxychloroquine and chloroquine. I don’t agree that either is *very* dangerous. The risks are well known exactly because both have been used for a long time. Chloroquine (definitely more toxic) has been used for decades.
Are you aware that Covid 19 is a dangerous disease which has killed people ? In the elderly the death rate is very high.
The recent Nature article is not the only evidence relevant to attempting to predict the effect of hydroxychloroquine on Sars Cov2 . The reason is that there is also work on original Sars. Evidence from one Coronsavirus is not proof about another, but it does effect estimates of probabilities and expected benefits and costs.
I think it is clear that hydroxychloroquine should be prescribed now for Covid 19. Many doctors agree and are doing so.
Always decisions under imperfect information (that is decisions) should be based on estimates of probabilities. If the argument that, with the benefit of hindsight you might wish you hadn’t done that so don’t do it were accepted we would never do anything.
I know the FDA view is that evidence short of a statistically signficant effect on the principal outcome measure of a phase III trial should be treated as 0 evidence, as nothing.
I also consider this to be completely insane (as I have written for years).
I don’t want to explain, but for me this is very personal (that’s why I know about side effects and risks)
https://www.bloomberg.com/news/articles/2020-03-21/nigeria-reports-chloroquine-poisonings-after-trump-praised-drug
Dilbert:
And what does the article say? A bunch of people took the meds beyond guidance. Either drug is safe when taken under medical guidance.
Tylenol is a very dangerous drug. If taken in amounts above those recommended, it can cause liver damage up to and including death.
Lots of drugs are dangerous in excessive amounts. There is a pharmacological term called “therapeutic index,” which refers to the concentrations above which are therapeutic but are below the toxic concentrations.
There’s a old adage in pharmacology: the dose makes the poison.
When taken in recommended dosage, hyroxychloroquine is remarkably safe.
Joel:
You appear to have a microbiology or some type of healthcare background from comments in the past. You are correct in your comment. My background is in the manufacture of pharma and healthcare supplies. I appreciate your speaking out.
Thanks, Run. I have a BA in microbiology, a PhD in genetics, and was an NIH postdoctoral fellow in molecular biology. I’ve been a professor of biochemistry and molecular biology at a research medical school for 33 years. I’ve authored or co-authored over 100 scientific articles that have been cited over 7000 times. But enough about me . . .
Hydroxychloroquine is effective in inhibiting SARS-CoV-2 infection in vitro is sort of like saying it is phase I clinical trials. Kevin Drum does not have this wrong at all. Now – this may be interesting: A recent case report showed that treatment with remdesivir improved the clinical condition of the first patient infected by SARS-CoV-2 in the United States2, and a phase III clinical trial of remdesivir against SARS-CoV-2 was launched in Wuhan on February 4, 2020. Those trials may be completed by May. Tune into 60 Minutes tonight as they have a report on all of this. Of course, reporters like economic bloggers are not biopharma scientists or medical doctors.
Thanks for the tip on 60 Minutes
“Lots of drugs are dangerous in excessive amounts. There is a pharmacological term called “therapeutic index,” which refers to the concentrations above which are therapeutic but are below the toxic concentrations. There’s a old adage in pharmacology: the dose makes the poison. When taken in recommended dosage, hyroxychloroquine is remarkably safe.”
Joel – a good point but efficacy is another issue. With this “recommended dosage” would that be enough to effectively treat this virus? I honestly do not know but neither does Trump. Which is why he should shut up and let the professionals speak.
Gentlemen. As a complete moron on this topic (I’m a physicist) it makes sense to me that it is all about the proper dosage. I have heard that for this application of the drug there is a rather narrow window between what has shown to be effective and what is potentially very harmful. Any comments from its advocates?
Some answers SW:
Much of this is NOT directed at you. I am filling in some gaps in the conversation here.
Here is the dosage for other usage. hydroxychloroquine sulfate If everyone” goes through the different sections and READs, I think they will learn much about the drug in question. Dosage appears to be weight related with an upper limit. There is a black box warning on this drug which is a warning (for those who may not know).
Chloroquine May Fight Covid-19—and Silicon Valley’s Into It
There probably not a better place to test a product than in real time environment whether it was approved in clinical trial or not for a specific usage. FDA approved it for Malaria, Rheumatoid Arthritis, Systemic Lupus Erythematosus, Porphyria Cutanea Tarda (Off-label). There was real time usage in China and it worked as reported To Kevin and the naysayers, if there is nothing else approved AND also in adequate supply, you go with what you have or you let them die. South Korea also recommends the use of HCQ or Plaquenil as well as other drugs. South Korea experts recommend anti-HIV, anti-malaria drugs for COVID-19. So if you object to China, I have offered up Korea and the US using HCQ. You can use the Medscape document for dosage and warnings.
SW, I am a complete moron on all things science including medicine but like the efforts to bend the exponential curve through social distancing, my understanding of the way the drug works against the virus is by preventing it locking onto cells thereby giving antibodies a better chance of overcoming the virus. If that is correct then there really is not a set therapeutic dose which is a “cure” but rather a range of dose which is more or less effective. If that is right I would think you would dose close to where the risks of toxicity and side effects begin to climb. I think that we are calling for use of the drug without further studies in the critically ill patients who have a high risk of dying without treatment especially if there is no hospital bed or ventilator to sustain them while their antibodies try and fight back.
Terry:
I posted the dosing for other diseases in my comment to SW. There are also the warnings within that link which can easily be found.
A couple of points:
1. In vitro testing isn’t like a Phase I trial. Phase 1 trials are for safety.
2. The very limited testing in infected humans suggest some efficacy in blunting the severity of infection. Numbers are small and the observations to date aren’t dispositive.
3. With all drugs, the key is the therapeutic index, the window between threshold of efficacy and toxicity. With acylovir, the therapeutic index is large. With AZT, not so much.
4. Why doesn’t Trump shut up and let experts speak? Because Trump only cares about Trump, not about America. His only channeled aspiration at this point is to control the news cycle. As long as he remains the topic, it doesn’t matter what people say, he’s winning. When people ignore him, that will change.
Joel:
Few pharma and micro guys around here. Please keeping answering statements with sound information.
NY’s excellent governor Andy Cuomo is giving us his daily briefing. Lots of interesting information on hydroxychloroquine. NY will start using it on COVID-19 victims starting Tuesday. He notes people in Africa were already taking it to avoid malaria. He also notes COVID-19 is not rampant in Africa. More evidence that it may work he asks? Interesting!
Joel – OK in vitro really means outside a living organism, which often means a test even before phase I. Lots can be learned but until we test within people, efficacy issues are still murky. BTW – I agree totally with your last point. I trust people who know what they are talking about, which includes you but definitely excludes Trump.
RI DOH just released new guide line under emergency order for off label prescribing. I assume they are attempting to allow and even promote (?) the use of these medications.
https://health.ri.gov/publications/legislation/Off-label-prescribing-ORR-Submission-03.21.2020.pdf
What allows virus to enter the resiratort tract epithelial cell via endocytosis? Perhaps it is the initial cytokine reaction which quinine is known to blunt. Quinine is a cheaply produced pharmacological. Perhaps the Chinese have used the agent as a prophylactic to mitigate against the initial endocytosis of the virus on the receptor protein in its health care workers and those in contact with the affected population.. No endocytosis, no replication of the RNA virus, and the positive feedback system is terminate – a desired outcome. Are the reports of no more positive testing in China fake news or reality?
G Lammert MD FACEP
China scrambles to stop rise in imported Covid-19 cases I think any nation would be hard pressed to say “no” new cases. I would be interested to see trend. Here are enough charts and graphs to keep you happy. China still has new cases as shown here 83 as of the 22nd. Growth: Country by country view
I hope this helps. I have other data if you wish. Just ask.
Bill
My understanding is that chloroquine is an ionophore for zinc. Zinc inhibits the coronovirus reverse transcriptase, inhibiting the viral replication cycle.
As noted I am a complete moron when it comes to science and I want to thank those who are not morons for the information they are providing. I do not want to get the virus and I equally or more do not want to spread it. Does anybody know the temperature range which the virus can withstand on hard surfaces—I am regularly wiping down outside doorknobs as well as indoor and have had outdoor temps in the teens. Am I correct that bleach kills the virus on hard surfaces? What about rubbing alcohol on oral thermometers? I have washed my hands with soap for 2 run through of Happy Birthday so many times my skin is getting very cracked but I still understand that and keeping social distancing are the best strategies to follow other than living alone as a hermit in a rural setting with a year’s worth of supplies. Thoughts?
Terry:
Not a complete, just half? 🙂
Stay safe . . .
How to clean your house to prevent the spread of coronavirus and other infections
Joel
Thank you.
Run you too. I think I see some flattening of the curve in Italy. Still way too many cases.