Guest Post by Willis Eschenbach
After all the people saying we shouldn’t take chloroquine because of the side effects, let me take the opportunity to say some words about that curious drug.
I moved to the Solomon Islands, north of Australia near the Equator, in 1984. I ended up living and working there for nine years. The Solomons host all four kinds of malaria—Plasmodium falciparum, P. ovale, P. malariae, and P. vivax. Unlike most parts of the world, at the time the four kinds of malaria in the Solomons were not chloroquine-resistant.
So I took chloroquine prophylactically once a week to prevent the disease. 500 mg (300 mg base), one pill every seven days.
After I’d been there maybe three years, I thought “I don’t want to take this forever. If I get malaria, I’ll cure it, that’s what medicine is for”. So after having taken well over 100 doses of chloroquine, I gave it up.
Of course, after stopping chloroquine, I got malaria. It is a most curious and devious houseguest. Malaria has a bunch of forms, all with different shapes and different abilities, and it changes form like we change shirts. When it hits your bloodstream, it streaks for your liver as fast as it can. Along the way, it is shedding parts of its skin layer. These skin bits occupy and distract a large number of antibodies, which recognize enemies by their skin surfaces. This allows more of the malaria parasites to make it to the liver. When it gets to the liver, it changes form.
After living for a bit in the liver in that new form, it changes form again and goes back out into your bloodstream and gets inside the red blood cells. Where, of course, it changes into another form.
Unlike the other forms, this latest form can reproduce. It starts to produce thousands and thousands of descendants, which eventually rupture the red blood cells and re-emerge into your bloodstream.
Until that point, you don’t even know the tiny criminals have invaded your corporeal mansion. But when they rupture the red blood cells, your body gets the full-blown malarial crisis, shaking and sweating, chills and fever at once. I’d always thought stories about people’s teeth chattering in sickness from the chills were exaggerations.
I was very wrong.
Now, at the time we were living on a 280 acre (110 ha) coral atoll island called Liapari Island, way out in the outback. Here’s the island, on the right …
The Solomon Islands are in the middle of nowhere, north of Australia below the equator. Western Province in the Solomon Islands, with the Western Province capital at Gizo Island, is even more nowhere. And Liapari Island, 17 miles (27 km) by water from Gizo, is the very heart of nowhere.
Fortunately, my gorgeous ex-fiancee is a family nurse practitioner. The doctors there advised quinine. So she took the company outboard skiff, drove it seventeen miles to Gizo, and brought back the quinine. I took the prescribed dose. Horribly bitter pills.
Well, I’m here to say that the damn quinine cure is far worse than the disease. It adds bad pain and weakness on top of chills and fever. I recall that at one point it took me about thirty seconds of hard work just to sit up in the bed. When I laid down, I thought “I can’t be that weak! I just can’t be! It can’t take that long just to sit up!”
So I tried it again.
45 seconds that second time. Crazy weakness and pain. I’d never felt anything like the combination of malaria and quinine, and I definitely don’t recommend it no matter how bored you are.
After that, I never took quinine again. I would take its chemical cousin, chloroquine, instead. But this time I was taking it curatively, not preventatively. It was not fun in the high doses, but it beat the malaria back, and it was much more tolerable than quinine.
Finally, after suffering a couple more bouts of malaria over the next couple years, my mad mate Mike told me that when you feel malaria coming on, and you can definitely can feel it coming on, to take three weekly doses at once (1500 mg, or 900 mg of base), then the same thing 24 hours later, then the same thing on the third day. He swore it fended off the malaria.
So I started using his plan, and I never got full-blown malaria again. Just take nine weeks worth of chloroquine in three days, it aborts the onset of the chills and fever, no problem.
In addition, at the time, I knew dozens and dozens of expatriates in the Solomons and maybe half or more of them used chloroquine for either prophylaxis or cure of malaria.
In summary: yes, as with any medicine, some people suffer side effects from chloroquine. But it is widely tolerated. In addition, it’s cheap because it’s been used since the 1930s, so it’s been off-patent for decades, and the side effects are well known
Do we know scientifically if it works for COVID-19? Nope. But I’ll guarantee you that if I get the ‘rona, I will take chloroquine and azithromycin and zinc. Nothing to lose, everything to gain, and Fauci is both mad and destructive to argue against it.
And to close out the story of the madcap transformations of the malaria parasite, we left it swimming in our bloodstream after rupturing the red blood cells. From there, a mosquito removes it from your body with its magic hypodermic needle, and it moves into the mosquito’s stomach where … yes, you guessed it, it transforms itself once again into a new kind of malarious being. And when the mosquito bites another person, it injects that form into your bloodstream, whereupon it starts racing for their liver to start the cycle again.
There is one final oddity of this most odd of life forms. Sometimes, P. falciparum vivax malaria can … yep, you got it … change into yet another form. It does this in the liver, and after changing forms it promptly falls asleep for maybe a year. Or two. Or more. This form goes by the absolutely wonderful name of a “hypnozoite”, after Hypnos, the Greek god of sleep. Hypnozoites are the source of the world-famous recurrence of malaria years, occasionally decades, after leaving the malarial zones.
When one of the hypnozoites wakes up after a two-year nap, I assume it stretches, yawns, looks at the other still-sleeping hypnozoites, and of course, it being malaria and all, just for fun it changes form. No longer a hypnozoite, it jumps into the bloodstream, reproduces inside the red blood cells until they burst … and that is how after I’d left the Solomons and had been living in Fiji for a couple of years, I suddenly felt that awful familiar feeling.
And being an honest man I must confess, at that moment I said very bad words. Not only that, but I engaged in needless and ultimately pointless vituperation, casting unpleasant but extremely satisfying aspersions as to the ancestry of the whole tribe of mosquitoes and malaria in all their evil blood-sucking cell-destroying forms.
I had been convinced at the time that I was done with malaria, but nooo … my main medical squeeze had to go hunt for chloroquine, there’s no malaria in Fiji. And once I got cured of the immediate malarial relapse, I took another drug that in theory kills the remaining hypnozoites, and me and malaria, we parted ways for good. At least I sure hope so.
And that’s my story of chloroquine and the reason why I say that anyone who gets the virus should at least try it.
My best to all, stay well, wash hands, don’t invite any strange bats to dinner, don’t touch your face, or your bat’s face for that matter, wear a mask, avoid crowds, you know the plan …
w.
PS- Regarding schools as centers of infection, the Solomons uses the British system of boarding schools. Grade school kids go from their villages to the local boarding school, which is often on another island, where they spend the entire semester.
And we always had to gird our loins and break out the mosquito repellent when the kids all returned at semester break, because invariably they brought a surfeit of malaria back with them …
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MedCram update 34: https://www.youtube.com/watch?v=U7F1cnWup9M&lc=z22xzjmqfynbz13xg04t1aokgtbmjgmcczqfvwlfpt4ibk0h00410.1586313354967628
Chloroquine and ZINC is the key. The ionophore allows more zinc into your cells than the normal zinc transport system does.
Doctors are not comparing HCQ to treatment X. They are comparing HCQ to “do nothing”. So in effect people are saying “don’t use HCQ because it is dangerous”. Well, COVID-19 is dangerous. Are you suddenly removing the danger of C-19 by not taking HCQ.
The press is arguing a false equivalence. And ignoring that HCQ is safer than CQ.
While in the British Army, Royal Signals , in Burma, 1946 to 48 we took a anti Malian drug. Much later while in Papua, New Guinea Police 1956 to 73, again we, wife and children, we were all on a anti malarian drugs s and never sick. No side effects.
I suspect that there are two reasons why we are not told to use it, its way out of patient so the big Pharmercial Companies are not interested, and second the Doctors have this obsession to not harm the patient, even when they are dying,, wanting years of testing.
VK5ELL MJE
So I take plaquinel for arthritis… because it is effective against some forms of arthritis… I’ve been taking 400mg of this stuff every day for close on 15 years…
Anyone have any thoughts or ideas on the efficacy of chloroquine vs Covid-19 when the person already takes the drug for other medical reasons??
We spent so much time focusing on air thinking COVID-19 is a SARS virus.
From what I have read we seriously goofed. It seems to attack blood cells and the resulting low oxygen state in the body is what is causing the lung damage. Which ventilators only make worse.
Can’t help but think of this quote from the movie Andromeda Strain.
Dr. Hall: “Air doesn’t matter! Blood does. That’s the answer.”
That’s what I have been reading too, and those who are O+ seem to be less affected by it.
“Air doesn’t matter! Blood does. That’s the answer.”
If so… then how to oxygenate the blood fast enough to mediate lung damage? Get blood O2 back up above at least 93+%? If not some expensive transfusion or adding O2 to one’s own blood by machine infusion?
Hyperbaric Oxygen Chamber ?
Just a shot in the dark.
The Mayo Clinic has a Department devoted to it’s use.
https://www.mediamatters.org/fox-news/fox-news-has-promoted-hydroxychloroquine-nearly-300-times-two-week-period
“unproven drug”
That treatment against a virus is unproven just like almost vaccines are unproven. There is no randomized testing required for vaccines anyway. Yet the Vaccine Church has no objection against MANDATORY vaccination. These people are crazy.
[snip that’s enough. you may disagree with a poster but personal insults of this level are off limits ~ctm]
@mods
DO
SOMETHING
Jim
You are out of line! There is an old saying that when you point a finger at someone, there are three fingers pointing back at you.
[snip that’s enough. you may disagree with a poster but personal insults of this level are off limits ~ctm]
“Horribly bitter pills.” Understatement. I took a weekly dose of chloroquine as an AFS student to Mombasa, Kenya in 1983. My pills were accompanied by a piece of bread with about half a jar of strawberry jam on it, washed down by copious amounts of very sweet Swahili tea. And then I would roll around and gasp at the bitterness of those pills. On a scale of 1-10 of bitterness, chloroquine is probably about 170.
That shows it works. It has been scientifically proven that the nastier the medicine, the more effective it is.
Why did you let them touch your mouth? We would throw them down our throat after a cup of cream, never tasted anything. 1972 Vietnam
Thank you for your always educational and entertaining posts. I am truly blown away by the many bristlingly smart, knowledgeable, generous-minded people who post on this amazing blog.
I have a bottle of anti-malarials that were prescribed for some work I did in Minas Gerais, Brazil in 2017. They are a combo of Atovaquone 250mg and Proguanil HCl 100mg, the latter is the old Paludrin my family and I took in Nigeria in the 1960s. The molecular diagram looks like the Quinine/chloroqine one including a couple of hydoxide ions. I’m not sure they work but by golly I’m prepared to take them if I get symptoms.
The ‘woke folk’ are going to kill us with their anti-chlorquine fake news because of anti-Trump. In Canada, doctors have been warned not to prescribe this stuff for Covid. Canadians should tell their doctors they are going on a jungle trip an get the stuff. Maybe the Yellow Fever shot you are obliged to get has a synergistic effect, too!
Willis
A nice and entertaining story about malaria. I appreciate most of the sleeping parasite story, that it seems to linger, quiescent until some time in the future, and, at times, inopportune times, for a recrudescence. Popping up as fever and shaking chills while in Northern Minnesota and health care practitioners not sure what is going on until an imported pathologist, from a land so far away, does a thick smear of blood and lo and behold, malaria. Then, the ensuing morning, on morning rounds for the medical practitioners: “have you ever traveled outside of the United States? if so, where?
Great post. I first took chloroquine when traveling in Africa in the 80’s. Hated it. Made me anxious and seemed to interfere with a good nights sleep. Stopped taking it when we were in the Saharan desert, but always when in jungle areas.
Fast forward a couple of decades. Took a trip to Indonesia and was prescribed Mefloquine (Lariam) as an anti-malarial by Kaiser doctor. This drug was developed during the Vietnam era as a “better”prophylactic than chloroquine and widely given to those serving in that arena. What a nightmare. Literally. Complete loss of short term memory and crazy night sweats and nightmares. I’m not prone to psychosis, but was on the verge pretty quickly. Like Willis, chose to risk Malaria rather than losing my mind.
Wonder if it works on Covid 19. Still would never take it again.
Thanks, Willis, for that fascinating account of the parasite’s life cycle. In the 70s, I spent a couple of months in Papua New Guinea. I took chloroquine weekly, as advised, but nevertheless experienced a few bouts of malaria upon my return to a temperate climate. It happened on and off for a few years. The symptoms were always the same. At about 5pm (it was probably triggered by the lower temperature at that time) I would start to shake violently (yes, your teeth do chatter and your skin does turn yellow) and sweat profusely. This would go on for about an hour and then you would throw up and be left with a raging headache. This would happen daily for four or five days at a time. I eventually found a doctor who knew tropical medicine and he prescribed Camoquine, which instantly put a stop to the daily bouts. Every time I had a recurrence the Camoquine would knock it over quickly and without and complications or side-effects. After about five years I ceased having the episodes. It’s been decades now and I have never had a recurrence, although I have heard of people who have had it for life.
Rum!
Not to go to far off topic, but relating to your previous post, have you seen the materials released by Minnesota in conjunction with its model. They are found here, https://mn.gov/covid19/data/modeling.jsp. Not bad in some ways, but most interesting and to your point, note that there is almost no difference in deaths across mitigation strategy scenarios. Also note that in the briefing they acknowledged doing no studies or analysis of the economic and non-economic harms of the shutdown order. Be very interested in your review of the materials.
Jeez, after reading this story I want to start taking Hydroxychloroquine just to be able to sleep at night – hiding in my blankets, listening for the dang mosquito in the room!
There has to be data by now that supports (or disproves) the effects of hydroxychloroquine. If it were highly effective then it should be easily evident. I am losing hope that it will prove to be effective. Guess we all just wait on the vaccination in a year – bleh.
re: “I am losing hope that it will prove to be effective.”
Can I ask: What planet did you just beam in from?
Oodles of data point to no benefit, just not for this exact virus, which is the only reason the people that know about such things have not spoken up forcefully.
Because they were being scientific.
Because they will wait for scientific evidence for this particular disease and this virus.
If there is literally nothing else to try and nothing to lose, it does not matter.
But neither of those things are really true here.
We have right to try laws, which will give a lot of people hope at times, while it is killing them.
No one really knows, because this is a new virus, and this could be the one virus on God’s green Earth that these drugs will kill.
Maybe.
(Just like maybe the WAIS is about the slide into the ocean tomorrow.)
They have value as anti-inflammatories and immunomodulators.
They are inactive in vivo re viral replication.
I have posted evidence day after day and week after week.
I even spoon fed it to the people that kept insulting me for knowing what I am talking about and keeping an open mind.
“Oodles of data point to no benefit,…”
What data are you looking at, Nicholas? All of the in vivo trials carried out point to viral load reduction at least.
I have seen only one flawed, small sample, Chinese study which suggested little efficacy, and one anecdote about a doctor somewhere who decided to stop using the treatment after some unspecified adverse reactions from an unspecified number of patients with no metadata given. What else do you have?
Against that, there was a randomised clinical trial in China (https://www.medrxiv.org/content/10.1101/2020.03.22.20040758v3), and clinical evidence from France, Spain, Italy, Bahrein, S Korea,Malaysia, Brasil and the USA.
In Italy, the national health authority authorised treatment with HCQ/Zinc/Azithromycin on the 29th March. On 4th April, they reported that they had spare ICU beds available for the first time. The number of patients in ICU has continued to decline dramatically.
In Brasil, Dr Paolo Zanato from Prevent Senior, in an interview with Portal Brasil Without Fear said;
“In São Paulo, the Prevent network had 96 deaths from coronavirus until March 22, almost half of all deaths reported by the government of São Paulo. Today they have only one person in the ICU. Since Prevent adopted this protocol, it has not registered any more deaths from coronavirus. And the people who had a problem are those who entered this protocol late, already with advanced disease.
“Two important points in this protocol. The use of tomography to know when to apply the medication and the use of Hydroxychloroquine associated with Azithromycin and Zinc.
Hydroxychloroquine should be administered at the very beginning of the disease, from the 2nd to the 4th day of the appearance of the first symptoms, such as fever, cough, runny nose and breathing more than 22 times per minute. People who manifest this condition should receive the medication at home. The drug is inexpensive and has few side effects.”
None of this anecdotal data is a substitute for a large scale, randomised, double-blind clinical trial, certainly. However, it is unlikely that such trials will yield useful data for several months, and, in the case of the European trials, it seems like HCQ is deliberately being set up to fail. The protocols call for its application only when patients are at death’s door.
In the meantime, most doctors are voting with their prescription pads. As one European pharmacist commented wryly : “It’s amazing the number of people who have suddenly developed rheumatoid arthritis.”
kribaez
You recommended, “Hydroxychloroquine should be administered at the very beginning of the disease, from the 2nd to the 4th day of the appearance of the first symptoms, …” After a long life of observations, it has been my experience that when I have had upper-respiratory viral infections, I typically get better on my own within 3 to 5 days!
The critical thing is that many on this blog are downplaying the potential side-effects of a drug that may not work, but is being touted because it appears to miraculously ‘cure’ COVID-19 within the period of time that most people with strong immune systems will commonly overcome similar viral infections. If it were as simple as holding one’s breath and drinking a glass of water to cure hiccups, I’d say “Go for it!” However, most are in denial about the potential that they might be one of the small percentage that are particularly sensitive to this drug. What is worse, those who are not physicians are trying to persuade others that there is no risk based on either personal experience or pure ignorance. It is irresponsible.
Clyde Spencer, are you a treating physician? Do you have credentials similar to Didier Raoult?
Also, Clyde, this is not about ” it has been my experience that when I have had upper-respiratory viral infections, I typically get better on my own within 3 to 5 days”
It is about preventing a LOWER respiratory viral infection… leading to pneumonia and potential death.
Jim
No, I’m not a physician, and I’m pretty sure that you are not either. If Raoult posts here, I will respect his opinion, but reserve the right to question him if he were to say something illogical. An important point is that I’m not advocating a treatment, but instead, I’m following the ‘Prime Directive’ of physicians: “Do no harm.” That is, I’m suggesting caution in the light of known potential problems with chloroquine and HCQ for a minority of users. I’m concerned that many of the posters here are advocating treatments they have read about, are dismissive of known problems, and are willing to accept claims of efficacy without question, that, if they were about climate, they would be complaining against quite loudly. I’m suggesting intellectual consistency and restraint in advocating things that are beyond your expertise.
re: “I’m concerned that many of the posters here are advocating treatments they have read about, are dismissive of known problems, and are willing to accept claims of efficacy without question”
My God man, you’re nearly as stupid and dense as ng. MOST of the ppl commenting have READ the reports, many reports, UNDERSTAND the science and are COMMENTING from an informed opinion. They don’t need a NANNY like you “urging caution”. We’re adults here, and a LOT of us have held significant technical positions in our lifetimes, meaning, we understand detail and complexity. I don’t think you should be commenting here (my opinion), maybe a Yahoo board or back to some obscure subReddit would be a better ‘match’, and THEY could probably use your nanny-ing to boot.
UV Meter
You said, “It is about preventing a LOWER respiratory viral infection…” I know that very well, because I’ve often developed a secondary bacterial infection, lower down, that required antibiotics. The point is, for those who have a strong immune system, if they can defeat any upper respiratory viral infection in a few days, then there is probably little risk of a lower respiratory viral infection. Those who need intervention are those who could not shake it off on their own. The point that I’m trying to make is that those who get well very quickly with HCQ may well have gotten well anyway. We will never know when we administer drugs that have not been rigorously proven to kill the virus. It is whistling in the dark!
Clyde,
You wrote:- “You recommended…”
Please read my post again with some care. I am not recommending anything. I am merely pointing to data sources. The recommendation does not come from me. It comes from the leading physician of the main clinic in Sao Paolo where they have been using this treatment for several weeks now. The question I am posing to Nicholas is a genuine one. Where is he finding negative data against HCQ?
kribaez
My mistake. I missed the quotes and thought that you were making the recommendation.
Jim
You insulted me with, “My God man, you’re nearly as stupid and dense as ng.” Now that you have provided an excuse to fire me from my command, perhaps you should resign. 🙂
Stupid I’m not, and I’ve never been accused of being dense — except by people who resort to ad hominens when they don’t have an adequate argument. You have already had a couple of comments deleted. Are you trying for a third?
Jim sez:
“MOST of the ppl commenting have READ the reports, many reports, UNDERSTAND the science …”
And he wonders how anyone could disagree with his knowledge of “the science”?
Wow.
Just wow.
But this is the guy who gets vitriolic at anyone who doubts his belief in hydrino energy.
kribaez,
If you want to take a small part of one sentence, and then create a straw man by ignoring what I said in the rest of the sentence, I have nothing to say to you, except, please do not misquote me.
If you just got here and have not seen the last two months of this conversation, then I am not surprised you are lost.
Go back and catch up.
I am not going to correct your straw man argument, or repost information that has been posted over and over again.
Grow up.
BTW…you made several false assertions in the rest of your disjointed and incoherent post.
Try to speak accurately and truthfully.
I do.
What kind of data could show that corona vaccination is a sound idea?
Or even suggest that?
Why don’t you request randomized trials showing the real benefits of vaccines?
niceguy
Why would that be necessary when polio has been eliminated in first-world countries and smallpox has been eliminated in the world?
Robert missed the bit you have to wear the aluminum foil hat to get the full effect.
Enlightening post and I rather like the way this gorgeous ex fiancee crosses the story every so often.
This discussion about the use of potentially helpful alternative treatments is a battle that Pres Trump started when he was candidate Trump.
I lose no love on the FDA so rather than say more I will simply get my hat.
The FDA simply makes sure that pharmaceutical companies don’t make $1B/year by advertising and selling a drug that haven’t been proven to be safe and efficacious in placebo-controlled or comparator-controlled double-blinded clinical trials. They do the same thing that Steve McIntyre did to those using tree-rings to prove that a Medieval Warm Period didn’t exist. He saw that the tree-ring sites chosen were cherry-picked after the fact, not selected for study by some unbiased method.
There is nothing wrong with terminally ill patients who have no other options being given a right-to-try an unproven treatment. It would be unethical for a drug company to advertise such drugs or for politicians who have no medical expertise to do the advertising for them. However, entering a hospital with COVID-19 is not a death sentence. Boris is recovering, Tom Hanks survived. However, the prognosis could turn grim in a few days. With too little oxygen reaching your brain, does it make sense for you to decide whether to take an unproven drug being touted in internet chat rooms or tweeted by a president seeking to re-assure voters? Should a frantically worried family member make that decision? This law permits this – but don’t expect a lot of rational decisions to be made. Just like the decisions made at the infamous wild animal “wet” food market in Wuhan that may have started this epidemic, where affluent Chinese citizens sought increased virility or better health.
Every year the WSJ has an editorial about how the big, bad FDA is bankrupting an small pharmaceutical company by not approving a drug that failed to show efficacy using the pre-determined standards in the pre-determined patient population. Someone on the board of the company (who has been given shares in the company) is probably friends with one of the WSJ editors. The sponsors have cherry-picked a subset of patients or selected new endpoints that show efficacy, but there are thousands of possible ways to perform such cherry-picking and one of those ways is likely to show efficacy at the 95% confidence interval simply by chance. The FDA – correctly – want a new clinical trial using only the patients and endpoints the company believes will show efficacy and the company doesn’t have the money. Is this a tragedy for both patients and shareholders? No. If the sponsors re-analysis of the clinical trial data is really promising, the drug will be acquired by one of dozens of highly competitive pharmaceutical companies and get a second chance. Take Erbitux for example, the drug that failed its first large-scale clinical trial – and infamously sent the CEO of Imclone and Martha Stewart to jail for selling their stock based on insider knowledge of that failure – was developed by other companies and is now a highly successful drug with sales of $2B/yr. The drug was eventually approved on the basis of this modest efficacy:
“a trial involving 329 patients, of which 10.8% responded when Erbitux was used by itself, delaying tumor growth by 1.5 months. When used in conjunction with a standard chemotherapy treatment, irinotecan, 22.9% of patients responded and tumor growth was delayed by approximately 4.1 months.”
Patients had to wait to buy this drug for the three additional years it took to identify a patient population and dosing regime that would produce even this minimal level of benefit. Compassionate use programs were possible then – if the sponsoring company wanted to participate.
Thousands of physicians worldwide have successfully treated Covid-19 with HCQ. If it did not work, we would know by now. Everyone in the media is trying to undermine this administration. If they found one doctor claiming HCQ does not work, it would be the top story for days.
None of this is scientific, but it’s still true.
Jeffery P: Thousand of physicians bled sick patients for centuries without realizing it was hurting them. Doctors treating desperately ill patients want to believe they are doing everything humanly possible to save the lives of those patients – a perfect scenario for confirmation bias – remembering data suggesting that HCQ helped some patients and failing to assimilate other data suggesting failure. This is an extremely common human weakness. In medicine, we have learned that the only way to establish the truth about efficacy is through placebo-controlled double-blind clinical trials.
Americans who believe their country is on the wrong track find it easy to ignore fact Bernie’s socialism has been rejected in much of the EU and that wealth taxes have been tried and repealed there. Other Americans find it impossible assimilate the numerous weaknesses of Trump into their consciousness, and do stupid things like attributing justifiable skepticism about HCQ to an anti-Trump bias.
When/If the US per capital death toll from COVID-19 exceeds that of China when the 2016 election rolls around, I predict that many will blame the skeptical news stories about HCQ spread by the liberal MSM that caused underutilization of HCQ in America compared with China. They will ignore the fact that US doctors working in hospitals don’t make decisions about what drugs to prescribe based on what they hear in the media. They review the scientific evidence available and their local experience as a team with a leader who has read everything about HCQ. Trump’s opponents will blame his delay in calling non-essential workers to remain at home or work from home, but they will forget that Democratic governors and other foreign leaders were slow in making the same decision – because of the huge economic cost. With the number of cases doubling every few days, the cost of delay has been enormous. A more cerebral leader who listens to and places more value in government experts would have had a better chance of acting earlier, but decisions that need to be made over the next four years might be better made by someone who is more skeptical of experts and listens to his gut. I suggest we judge on the basis what happens next, by how soon and SAFELY we can get our economy re-started. This is a problem that every leader has known would be coming for more than a month.
I am shocked.
Does no one here know what happened?
Just gonna leave this here.
“Compassionate Use of Remdesivir for Patients with Severe Covid-19”
https://www.nejm.org/doi/full/10.1056/NEJMoa2007016
Well, I have waited over 24 hours, and exactly no one has said anything about Remdesivir except exactly one lukewarm reply to my post last night. (Maybe Greg is not a complete numbskull after all, just way too hardheaded and rude)
This changes everything.
The worst off patients now have a small chance of dying. 18% If confirmed. High confidence.
(Correction…a reread shows 13% of severely ill patients died. These were people on life support…the ones dying at rates of up to 78%)
The pretty badly off patients have about a 4-5% chance of dying. If confirmed. High confidence.
Patients not on oxygen or mechanical ventilation will likely have zero chance of dying. If confirmed. High confidence.
This is the game changer.
There is zero evidence chloroquine or HCQ has allowed anyone on life support to be extubated and go home.
Now those people have about an 18% chance, if confirmed.
It does need confirmation, but this was a careful and detailed look at the first people who took it when there was nothing else…perhaps the sickest of the sick at that time.
I do not want to be disparaging, but it is obvious almost no one, possibly no one, commenting here has any idea how to read the results of a drug trial.
No adverse events that were attributable to the drug.
The 8 people lost to follow up may have simply recovered and felt no need to go back to the hospital that treated them.
If confirmed, and there is everything to be hopeful for here…even if the results are only half as good…the odds of dying with this disease just went down by about an order of magnitude at least.
And that is average of all stages.
If and when approved, I do not see any reason why anyone would need to be let get to an end stage where the odds are only 18% and they are on a life support machine. If supplies can be stretched. The trial looking at 5 days vs 10 days is going to be a huge one…twice as many courses of treatment worth. Maybe 300,000 people, with another one to two million people’s worth by year end.
But I expect it will be a lot more than that…everyone will start making it under license that has the facilities.
Raw materials may be a bottleneck.
Also…every hospital in the world should have ECMO.
At present, US has a lot of them over 264 hospitals and adding more fast, some in B.C. Canada, a very few in England and Wales, zero in Ireland or Scotland, 40 hospitals in Germany, Poland has 47 machines, Sweden has 7 or more, Russia has a few hundred, Japan has over 1400, and China has at least 400.
No one else seems to have a single one.
You heard it from me first…this is huge, and only the supply will keep almost everyone newly infected from being cured quickly…although it is like there will be some non-responders, as there almost always is.
Even if only half as good as these initial results a game changer.
Il-6 drugs will save still more.
No one wants to pour too much cold water on malaria drugs, because anything is possible.
But if these drugs kill this virus, it is literally the only virus ever tested on, that it does that for.
It treats some symptoms, but adverse events may outweigh any benefit.
It is always good to be optimistic, but you have to have a real hard head to ignore all the hard scientific evidence that exists for this drug on other viruses, as well as 70 years of zero epidemiological data despite millions taking it.
And many deaths in places using it, and rising sharply.
And no trials halted by a DSMB for success.
And recall the place that had the first trial that started this?
Here is one of the doctors from there:
“Chinese Doctors at Coronavirus Hub Say Evidence on Chloroquine Is Inconclusive”
https://www.wsj.com/articles/chinese-doctors-at-coronavirus-hub-cast-doubt-on-chloroquine-as-cure-11586448660
What have we got to lose?
Only your life, if you did not take something that worked instead.
I wonder how many have and will still die and did not need to, by this inane focus on HCQ and frickin zinc!?
I expect few will even change their minds.
People decide what they believe and then lock their minds up tight.
Where do we know that sad story from?
re: “Remdesivir … I expect few will even change their minds. People decide what they believe and then lock their minds up tight. Where do we know that sad story from?”
Can you ‘lay out your case” as cleanly as MedCram does for Zn and hcq? Showing the method by which Remdesivir works at the cellular level? If you can, you will entertain an audience first and adherents second:
It is not my job to be a huckster.
Go watch Dr Oz and “Doctor” Rigano if that is what you value.
Do you think I am an advocate?
That is the mistake you are making, not me.
Interesting that appeals to authority are what sways you, and a convincing case for a “mechanism”.
You will find you and a lot of other people here have destroyed your credibility when it comes to demanding scientific rigor from warmistas.
Again, not my concern…but I find it terribly regretful.
Nicholas
+1
Don’t worry Nicholas your shares in Gilead will do just fine.
That class of antivirals that mess with nucleotides need to be carefully kept away from (potential) expectant mothers due to the potential risks of birth defects.
Thalidomide is also a very potent drug for a number of indications – but that’s not what it is remembered for.
Phil
Apparently you did not read the link I provided above. HCQ is not recommended for expectant mothers either!
For the record, I do not own shares or options in Gilead or any other stock right now.
I do not think they will make any money on this in any case.
I would think it unfortunate though, if anyone used anything but objective criteria in deciding what course of treatment to seek should they need a treatment, for COVID or for anything.
I would not use cost, who made something, or any other such trivial details.
What works and for what does some hard evidence exist for.
The question is hardly settled, but my ability to parse the difference between evidence and hopes and possibilities leads me have more hope than I have had, that good news will be forthcoming shortly.
Until that day comes, my personal plan is to avoid the virus like the plague until something has been proven to show efficacy and safety, and is available, in case I should have an unlucky spin of the roulette wheel if and when (I expect when, not if) I finally do wind up getting my turn to spin it.
It will be a while yet.
I am curious though…have you decided you would reject something based on what you have already decided, or your seeming dislike for some particular corporate entity, even if one you have decided you do not like is the one which proves best?
I will take what has been shown to work best if and when I need it, using all data and with particular attention to anything of a more scientifically gathered chain of such evidence.
I learned long ago that trying to guess about new drugs is a fool’s errand.
But clues are emerging.
I want more than clues, but that will not stop me from using inferential data…ALL of it, if need be.
Having said all of that and the below, I believe that the data released from Gilead in The New England Journal of Medicine on April 10th, along with the open letter from O’Day on that same date, is indeed far better than I had concluded would be forthcoming since no trials had been halted by the DSMB.
Time will tell.
There are a huge number of people in a large number of trials for all of the drugs discussed here and more.
We will be able to go back and compare results with who said what over the past few months.
This is way different than global warming.
We will soon know who knew what the %#&* they were talking about… and who did not.
Nicholas,
I am very surprised by your last post. You have generally argued that there was insufficient evidence to support the use of HCQ+ because the in vivo data came from clinical studies which did not meet the gold standard of being fully randomised, double-blind clinical trials.
Yet here you present the result of a study of remdesevir based on a small-sample opportunistic cohort with no control group – a study which was moreover funded by the manufacturer of remdesevir – and declare the result to be a game-changer. What happened to your argument about the need for carefully controlled trials? Your arguments then shift to advocacy divorced from cool scientific evaluation.
It was applied to the “sickest of the sick”. No, I think those guys are definitely dead.
No adverse events that were attributable to the drug. There are a total of 32 adverse events recorded, and 2 patients had the drug discontinued because of elevated hepatic enzymes. You should explain how you conclude that none of these were attributable to the drug.
The 8 people lost to follow up may have simply recovered and felt no need to go back to the hospital that treated them. Or they could all have quietly died.
There is zero evidence chloroquine or HCQ has allowed anyone on life support to be extubated and go home. I agree with you, but the claim is that early treatment reduces the probability of ending up on life support.
To be clear, I do believe that this might be good news. However, I am struck by the change in tone of your argument as you go from attacking the evidence for HCQ (we need gold standard to recommend a new treatment) to supporting what must still be considered “anecdotal” evidence for remdesevir. You are moving the goalposts.
I have never attacked the evidence of HCQ, I have pointed out the problems with the quality of recent studies of it in COVID patients, the safety issues, and the previous trials of the drugs with other viruses, including with SARS in mice, which were uniformly disappointing.
I was also one of the first, I think THE first, to point out that in the US, no approval from any authority is required to seek HCQ, because it is an approved drug and any doctor in the US can prescribe it if they see fit to. So all anyone who wants it needs to do is find a doctor who will.
But in this last post I am stating quite frankly that while hopeful, I am quite skeptical and not seeing any reason to be champing at the bit to be getting me some chloroquine.
If new data warrants, I will respond accordingly.
Too many people are unable to parse caution from scorn.
But if we are to go on the totality of evidence, the odds, in my estimation, are against HCQ and Chloroquine having direct antiviral activity, but it is known to be useful as an immunomodulator and anti-inflammatory.
I have posted over and over many types of evidence pro and con and how I size them up and why.
Remdesivir works in mice and other animals including primates with viral infections. It has extraordinary antiviral activity in vitro, against a wide range of virus types.
And now we have evidence that it has allowed many patients who were on life support to walk out of the hospital in proportion far greater than the stats posted by Monckton for people on mechanical ventilation from UK and from Texas.
Many reports have informed us that the odds of survival once on a ventilator are quite low, and that for all patients who are hospitalized, the overall fatality rate is far higher than was seen with these small number of patients getting remdesivir on a compassionate use basis.
I also am aware of the criteria for those getting approval for compassionate use.
They are:
Your disease is serious or immediately life-threatening.
No treatment is available or you haven’t been helped by approved treatments for your disease.
You aren’t eligible for clinical trials of the experimental drug.
Your doctor agrees that you have no other options and the experimental treatment may help you.
Your doctor feels the benefit justifies the potential risks of the treatment.
The company that makes the drug agrees to provide it to you.
More recently, the drug has been opened up for less strict usage called “expanded access”.
But this paper detailed just some of the first patients, who were given the drug in the period before expanded access. They were not eligible for any then existing clinical trials, or it was prior to any trial being offered in their locations. Specifically:
“This cohort evaluated data from 53 patients in the United States, Europe, Canada and Japan who received at least one dose of remdesivir on or before March 7, 2020, through Gilead’s compassionate use program. All patients were hospitalized with severe acute respiratory coronavirus 2 (SARS-CoV-2) infection and either an oxygen saturation of 94 percent or less, or a need for oxygen. The median duration of symptoms before initiation of remdesivir was 12 days. The majority of patients (75 percent) were men over the age of 60 years with comorbid conditions, including hypertension, diabetes, hyperlipidemia and asthma. Combined, all three of these factors have been associated with adverse outcomes of COVID-19”
These were mostly people with poor prognosis. They had been having symptoms for an extended period, an AVERAGE of almost two weeks, with the range from 9 to 15 days.
The average age of the group on ventilation was stated…it was 67 years old.
I could go throught the whole thing line by line to help you understand what I was able to glean after a VERY close look at all that was recorded and described.
These were ALL people with severe disease.
Some had been on mechanical ventilation for 8 days.
Many were elderly, many had numerous comorbidities.
I know how to interpret a hazard ratio.
I have a very good idea that this group was older, sicker, and had more comorbidities than the set of all patients in other settings that were hospitalized.
This report contains no blandishments…you need to be able to parse it carefully to understand what is implied by these results.
It is far more positive than it may appear.
Another key finding:
“Sex, region of enrollment, coexisting conditions, and duration of symptoms before remdesivir treatment was initiated were not significantly associated with clinical improvement.”
Think about that. We know that long duration of symptoms is bad in people receiving SoC.
We know that male sex is associated with worse outcomes.
We KNOW that coexisting condition is highly correlated with a bad outcome.
But not here…with remdesivir, those did not matter in people with severe disease and who were hospitalized for many days on average.
Age was by far the highest hazard ratio.
As for my assertion that none of the adverse events could be directly attributed to the drug, was the statement that “Mild to moderate liver enzyme (ALT and/or AST) elevations (23 percent, n=12/53) were observed in this cohort. No new safety signals were detected during short-term remdesivir therapy.”
Six of 34 patients on mechanical ventilation died. One of the one not on mechanical ventilation died.
Overall, 13% died.
Of those intubated on a ventilator, 18% died.
Now, what percentage have been shown to survive at this stage and with these particulars in any other circumstance?
I am not going to answer that…you need to look for yourself and arrive at a number you think.
I will quote one passage from the NEJM study regarding comparison cohorts in other studies:
“In a recent randomized, controlled trial of lopinavir–ritonavir in patients hospitalized for Covid-19, the 28-day mortality was 22%.10 It is important to note that only 1 of 199 patients in that trial were receiving invasive ventilation at baseline. In case series and cohort studies, largely from China, mortality rates of 17 to 78% have been reported in severe cases, defined by the need for admission to an intensive care unit, invasive ventilation, or both.23-28 For example, among 201 patients hospitalized in Wuhan, China, mortality was 22% overall and 66% (44 of 67) among patients receiving invasive mechanical ventilation”
Go that?
Overall mortality when 1 out 199 patients were on ventilation in one study was 22%.
The people in this study were far sicker.
Look at the data Christopher Monckton has reported.
Numerous info on mortality of people on ventilation is available from around the world.
Nothing approaches this at a similar stage of illness.
The ones who dies were old and sicker to begin with.
I am making inferences based on everything I have ever learned.
Confirmation is required.
If further data is on line with this, how does it sound to you?
These were all, according to compassionate use guidelines, people who were expected to die.
Lets discuss it again when we see clinical trial data.
If I am wrong, I will apologize for being a fool.
Until then, I will respond to any more questions you might have re my rationale and willingness to speculate favorably.
I do not want to be pessimistic about any other treatments, but if one single person who reads what I wrote makes a decision which helps the or someone they known survive, it is well worth it to me to stick my neck out and to be quite frank.
I am reassessing based on new info, and on what I see as a sense of unbridled and unjustified faith in malaria drugs.
My only goal post is life for as many as possible.
I am not telling anyone what they oughta do…that is a decision for a patients and their health care professional team.
I am only providing my OPINION of what the best of my knowledge is SEEMING to indicate.
Take it or leave it.
All the best to you and yours.
Kibeaz,
A few other things I did not mention.
Consider this all started with a small study out of China.
Now consider China has long since halted all use of the malaria drugs, according to doctors in Wuhan.
Pay attention to what they say and do not say.
Pay attention to the lack of good faith and personal promotion of such people as a certain French doctor, who just happened to leave out of his study results the person who died and the three who went to the ICU after getting his treatment, and the failure to disclose the disparity in the treated and untreated cohorts. Little details like that.
Also, I happen to know what a publicly traded company is and is not allowed to say before study results are published for all to see at the same time.
I also have a good idea of how expensive it is to run clinical trials.
I have no good way to give a dollar figure for what Gilead is spending on giving away all their supply, the manufacturing ramp up, and all the incredible number of studies they have initiated, but I will bet it is an eye-popping amount of billions of dollars.
Read the NEJM report, every word of it, two or three times, including all of the supplemental materials and the pres releases from Gilead and what doctors involved in the trials are saying.
Low key, just a hint, which by itself is very unusual.
Usually they say nothing and let the data do the talking.
re: “Pay attention to the lack of good faith and personal promotion of such people as a certain French doctor, who just happened to leave out of his study results the person who died and the three who went to the ICU after getting his treatment, and the failure to disclose the disparity in the treated and untreated cohorts. Little details like that.”
Do you have MORE information on top of this (since this paper was released) research paper:
https://www.mediterranee-infection.com/wp-content/uploads/2020/03/COVID-IHU-2-1.pdf
Because, if it is taken as _true_ in that paper what you wrote is NOT TRUE.
NOTE also the deaths recorded by Raoult’s organization here as a result of their work with hcq et al:
https://www.mediterranee-infection.com/covid-19/
The figure is up to 10 as of my writing this. Raoult (“the French doctor”) seems rather open with his papers, his studies and stats where as Nicholas McGinley provides no cites or supporting documentation whatsoever.
“no cites or supporting documentation whatsoever.”
Are you serious?
What exactly is it you think I made up?
You want supporting documentation?
https://news.yahoo.com/small-chloroquine-study-halted-over-121423352.html
So that Yahoo story discusses people with “severe disease” and that was used to suggest something negative about hydroxychloroquine, and shows what we already know. You should think about how it works and why and when it has been shown to be effective.
We know how it works, as a significant ionophore for Zn, and why it is effective in the right cases when used early enough. We also already know why it would not be effective when administered too late, since it works by disrupting the RNA replication of viruses with Zn within the cell.
If the body is already overwhelmed by the free rein of virus and its complications, the treatment will not address the virus’ already replicated. This study confirms all that we already know. It does not show that it is dangerous when used properly.
Clyde says: “You want supporting documentation?”
news.yahoo.com is documentation now ?
We do not know that Mario.
That is at best a fringe idea as to the mechanism for any benefit as an treatment for a viral illness.
Here is what doctors and medical researchers believe to be the case:
“Chloroquine:Mechanism
of action
Fusion and
un-coating
blockade, by
lysosomal
alkalization
[9,10];
Interaction
with the
ACE2
receptor [9];
“immunomodulation”?
Hydroxychloroquine: Mechanism
of action
Not fully
elucidated
but assumed
to be similar
to that of
chloroquine.”
***You are perhaps paying attention to people here and elsewhere in media and the internet who are by no means medical professionals, experts in physiology, microbiology, virology, immunology, or any relevant discipline.
The finding by some researchers that these drugs are zinc ionophores has never been demonstrated scientifically to be in any way related to their possible usefulness in treating viral illness.
In fact the whole question of them being antivirals at all is still, at best, weakly supported.
Extending this thought to what I am currently worried about, is that there are an awful lot of people who are not waiting for any evidence from any clinical trials for a scientifically derived base of evidence regarding these drugs and what they can or cannot do, and that besides for the public health implications of people waking unwarranted assumptions and becoming advocates for what may turn out to be a very harmful distraction, is the political implications: We are in a situation now, where it may well be that the Trump Presidency and who wins control of the US House and Senate may hang on the question of the efficacy and safety of these drugs for treating COVID -19.
I cannot personaly imagine anything more insane than what may possibly result from this unwarranted obsession based on extremely flimsy evidence.
That people here, who have spent many years talking about issues of scientific rigor, have so totally abandoned any effort or willingness to reserve judgement on an open question of medical science, is IMO jaw dropping, galling, and very worrisome.***
Beyond that, we now have a large number of people here and elsewhere who have abandoned all thoughts of civility or willingness to engage in reasoned discussion with anyone who does not believe as they do on any one of a number of topics related to this virus and this disease and certain medical intervention.
We have Trump supporters infected with a awful case of anti-TDS
We have skeptics of CAGW adopting the very worst parts of the warmista playbook and making it their own.
Right down to lumping anyone who differs in any way from some aspect of this new COVID meme as outside of their new cult.
Here is the source:
https://epidemio.wiv-isp.be/ID/Documents/Covid19/COVID-19_InterimGuidelines_Treatment_ENG.pdf
Sendergreen sez,
“Clyde says: “You want supporting documentation?”
news.yahoo.com is documentation now ?”
According to Jim, you tube videos are now “the science” re medicine, medical science, virology, pharmacology, virology, epidemiology…and anything else which supports what he wants to believe.
Contrary information is ignored and given zero attention or reply.
He has learned his warmista playbook and repurposed it well.
Nicholas: You said no to this statement I made:
“We know how it works, as a significant ionophore for Zn, and why it is effective in the right cases when used early enough. We also already know why it would not be effective when administered too late, since it works by disrupting the RNA replication of viruses with Zn within the cell.”
____________
You did not show me that my statement was wrong, other than saying “we do not know that”. The appealing to authority statement that one must be a medical professional distracts from the conversation, especially since there are medical professionals on literally both sides of this argument. So that fluff does not fly in a logical discussion.
As well, I am a process control engineer… every process is bound by things that can be understood by physics and chemistry and other sciences…
Zinc ionophores either exist or they don’t. I believe they exist. So let’s not argue that.
You believe there is no proof that hydroxychloroquine is a Zn ionophore? If we can get past that part, then the second part is:
Does Zn interfere with RNA replication or does an alkaline environment interfere with RNA production.
Since Zn++ in being carried by ionophore through the cell membranes, it turns an otherwise acidic cell more alkaline, then the alkaline theory of interfering with RNA replication or the Zn interference with RNA replication is what we’re arguing about.
I certainly believe that you do not know since you told me that. But your statement of “we” is incorrect.
No, you misunderstand Mario.
I did not say or mean to imply that these drugs are not zinc ionophores.
I am saying that being zinc ionophores is not known to be the mechanism by which these drugs have therapeutic value for treating people with viral infections.
Some effect being asserted or hypothesized is not knowledge.
Being an engineer, which is in itself a non sequitur, you ought to be aware of the distinction between something which is thought by some to be true, and knowledge.
I made no appeal to authority, I demonstrated that it is not generally taken to be true that the mechanism you assert is factual…hence it is not knowledge.
You rightly point out that appeals to authority are logically fallacious as evidence, but then you assert your personal credentials as being evidence of something.
An analogy would be someone saying “we know CO2 is a radiative gas, and that it traps heat which is warming the globe”.
Then saying they are a climate scientist so let’s not argue about it being a radiative gas, when what was being argued was not the radiative properties, but that heat trapping by CO2 being the cause of global warming counts as knowledge.
You will not find any place in any comment I have ever made that asserts or implied I doubt that these molecules are zinc ionophores.
If I said that these people who are medical professionals having a different view, means that they are correct because they are doctors, that would be an appeal to authority.
What I did was show that others do not share this view you have adopted as known.
Which demonstrates it is a belief that is not universally held, hence not knowledge. More like an unsupported hypothesis of a mechanism for antiviral activity.
To look at it another way…how many ways do these malaria drugs act as antivirals.
As many ways as can be asserted?
Ok, just one more…I think:
“This preliminary report describes the clinical outcomes in a small cohort of patients who were severely ill with Covid-19 and were treated with remdesivir. Although data from several ongoing randomized, controlled trials will soon provide more informative evidence regarding the safety and efficacy of remdesivir for Covid-19, the outcomes observed in this compassionate-use program are the best currently available data. Specifically, improvement in oxygen-support status was observed in 68% of patients, and overall mortality was 13% over a median follow-up of 18 days. In a recent randomized, controlled trial of lopinavir–ritonavir in patients hospitalized for Covid-19, the 28-day mortality was 22%.10 It is important to note that only 1 of 199 patients in that trial were receiving invasive ventilation at baseline. In case series and cohort studies, largely from China, mortality rates of 17 to 78% have been reported in severe cases, defined by the need for admission to an intensive care unit, invasive ventilation, or both.23-28 For example, among 201 patients hospitalized in Wuhan, China, mortality was 22% overall and 66% (44 of 67) among patients receiving invasive mechanical ventilation.7 By way of comparison, the 13% mortality observed in this remdesivir compassionate-use cohort is noteworthy, considering the severity of disease in this patient population; however, the patients enrolled in this compassionate-treatment program are not directly comparable to those studied in these other reports. For example, 64% of remdesivir-treated patients were receiving invasive ventilation at baseline, including 8% who were receiving ECMO, and mortality in this subgroup was 18% (as compared with 5.3% in patients receiving noninvasive oxygen support), and the majority (75%) of patients were male, were over 60 years of age, and had coexisting conditions.
Unfortunately, our compassionate-use program did not collect viral load data to confirm the antiviral effects of remdesivir or any association between baseline viral load and viral suppression, if any, and clinical response. Moreover, the duration of remdesivir therapy was not entirely uniform in our study, largely because clinical improvement enabled discharge from the hospital. The effectiveness of a shorter duration of therapy (e.g., 5 days, as compared with 10 days), which would allow the treatment of more patients during the pandemic, is being assessed in ongoing randomized trials of this therapy.
No new safety signals were detected during short-term remdesivir therapy in this compassionate-use cohort. Nonclinical toxicology studies have shown renal abnormalities, but no clear evidence of nephrotoxicity due to remdesivir therapy was observed. As reported in studies in healthy volunteers and patients infected with Ebola virus, mild-to-moderate elevations in ALT, AST, or both were observed in this cohort of patients with severe Covid-19.18,19 However, considering the frequency of liver dysfunction in patients with Covid-19, attribution of hepatotoxicity to either remdesivir or the underlying disease is challenging.29 Nevertheless, the safety and side-effect profile of remdesivir in patients with Covid-19 require proper assessment in placebo-controlled trials.
Interpretation of the results of this study is limited by the small size of the cohort, the relatively short duration of follow-up, potential missing data owing to the nature of the program, the lack of information on 8 of the patients initially treated, and the lack of a randomized control group. Although the latter precludes definitive conclusions, comparisons with contemporaneous cohorts from the literature, in whom general care is expected to be consistent with that of our cohort, suggest that remdesivir may have clinical benefit in patients with severe Covid-19. Nevertheless, other factors may have contributed to differences in outcomes, including the type of supportive care (e.g., concomitant medications or variations in ventilatory practices) and differences in institutional treatment protocols and thresholds for hospitalization. Moreover, the use of invasive ventilation as a proxy for disease severity may be influenced by the availability of ventilators in a given location. The findings from these uncontrolled data will be informed by the ongoing randomized, placebo-controlled trials of remdesivir therapy for Covid-19.”
Now, I know how they usually word these discussion, so here are things where I believe they are using careful language to telegraph what they cannot say out loud:
“…the clinical outcomes in a small cohort of patients who were severely ill…”
“controlled trials will soon provide more informative evidence regarding the safety and efficacy of remdesivir for Covid-19, the outcomes observed in this compassionate-use program are the best currently available data.”
“improvement in oxygen-support status was observed in 68% of patients, and overall mortality was 13% over a median follow-up of 18 days. In a recent randomized, controlled trial of lopinavir–ritonavir in patients hospitalized for Covid-19, the 28-day mortality was 22%. It is important to note that only 1 of 199 patients in that trial were receiving invasive ventilation at baseline.”
“…the 13% mortality observed in this remdesivir compassionate-use cohort is noteworthy, considering the severity of disease in this patient population…”
“… 64% of remdesivir-treated patients were receiving invasive ventilation at baseline, including 8% who were receiving ECMO, and mortality in this subgroup was 18% (as compared with 5.3% in patients receiving noninvasive oxygen support), and the majority (75%) of patients were male, were over 60 years of age, and had coexisting conditions.”
“…Moreover, the duration of remdesivir therapy was not entirely uniform in our study, *largely because clinical improvement enabled discharge from the hospital*.”
*patients who were severely ill*
*patients who were severely ill*
*patients who were severely ill*
*noteworthy, considering the severity of disease*
*noteworthy, considering the severity of disease*
*noteworthy, considering the severity of disease*
*largely because clinical improvement enabled discharge from the hospital*
*largely because clinical improvement enabled discharge from the hospital*
*largely because clinical improvement enabled discharge from the hospital*
Emphasis mine.
“contemporaneous cohorts from the literature, in whom general care is expected to be consistent with that of our cohort”
“Moreover, the use of invasive ventilation as a proxy for disease severity may be influenced by the availability of ventilators in a given location.”
So, what are they saying here, without saying it because they cannot?
Some of these people were not on ventilators because none were available?
Page 11 of the supplemental material.
Of the initial cohort of 61, one had some problem related to what sounds like a mistake by someone in the hospital.
7 of severely ill patients had no post 1st day data.
Why?
They said as much…they were improved and sent home.
If they died or got worse they would have been obligated to say so.
IMO.
13 stopped before getting all ten days worth, and why?
From above emphasis mine comments:
“*largely because clinical improvement enabled discharge from the hospital*”
Then is a description of each fatality, in detail, starting on page 14, narratives of death.
This describes people who were very sick with severe preexisting illnesses.
Some are very likely deaths due to cytokine storm, IMO.
Hence my opinion that IL-6 blockers may have save some more.
I could be wrong:
79 year old, kidney failure.
68 year old with diabetes, anemia, bipolar disorder,
hypothyroidism, hyperlipidemia, and allergic rhinitis. Morbidly obese with anemia and diabetes. Multiple organ failure. Cytokine release syndrome, IMO.
75 year old, myasthenia gravis and prostatic hyperplasia. Italy. Apparently they had no ventilator for him. He died without adverse events of respiratory failure. Just could not hang on.
72 year old, gastrointestinal cancer and diabetes. Multiple organ failure. No additional adverse events.
78 year old, no medical history could be obtained. Italy. Worsening condition after admittance to hospital. Multiple organ failure.
72 year old, no history reported. Worsening condition and invasive ventilation prior to treatment, hung on for 17 more days after beginning treatment, respiratory failure, acute respiratory distress syndrome.
77 year old, w/ medical history, including asthma. ARDS and multiorgan failure.
The rest survived.
Now, those sound like some very sick people to me. But it also sounds like several held on for quite a while after they were about to die before getting treated.
A larger number of “severely ill” patients walked out of the hospital within one to ten days.
Maybe as much as 250% more?
So…that is why I am hopeful.
How many of us are that badly off to begin with?
How would these 7 who died have fared with more timely treatment?
My guess is “better”.
Just a guess.
Thanks for the full response.
“Also…every hospital in the world should have ECMO.
At present, US has a lot of them over 264 hospitals and adding more fast, some in B.C. Canada, a very few in England and Wales, zero in Ireland or Scotland, 40 hospitals in Germany, Poland has 47 machines, Sweden has 7 or more, Russia has a few hundred, Japan has over 1400, and China has at least 400.
No one else seems to have a single one.”
That will result in a high death toll. A significant number of cases need ECMO. Especially cases of younger patients that get into a severe condition without any obvious reason. Those patients have very good survival rate with ECMO but die without it.
What’s the cost difference between the ECMO and a standard ventilator?
I am sure it is a lot of money difference.
President Trump has been criticized for “promoting” the Raoult protocol, but I don’t think he was for promoting the US cancer industry and the low rate of deadly cancers in the US. There is no randomized trial showing the US cancer industry is doing a better job by “lowering” the rare of deadly cancers, and a lot of evidence showing that it wrecks the live of many people by doing as much “prevention” as possible.
Is the drug store out of you medications again?
What are your qualifications, again?
None as far as we know.
You are dismissed, NPC.
Bingo niceguy!
Haha!
You so funny!
No but seriously…
Well, I guess you told me.
I sure would feel a lot better with you guys in my corner.
I’ll reassess…pronto.
Thanks for the feedback.
Willis, you wrote “Unlike most parts of the world, at the time the four kinds of malaria in the Solomons were not chloroquine-resistant.” Is that still true today or has something changed? Is there another drug used to prevent it in places where malaria has become chloroquine-resistant?
Very interesting read and very informative. I had no idea about the life cycle of malaria or that there are actual 4 different types. Fascinating.
It sure seems that the left doesn’t want Trump to be proven right about this.
Trump is no scientist, and it seems people on his own team are leading him off the cliff.
At least he has mostly qualified his advocacy.
Just think carefully about this sentence, and evidence, and what it means to “know” something”
“It sure seems that the left doesn’t want Trump to be proven right about this.”
My best interpretation is that the events and the TDS of the left has given some on Trump’s side a case of reverse TDS that may be almost as severe.
They so much want him to be wrong, so of course people on the other side just have to insist and hope like hell he is right.
Oh, not hope.
You know it, now you just have to prove it!
Anybody here read Brad Keyes’ essay?
“The stars of stage and screen recite the lines someone else gave them. So if their bespectacled, pocket-protected character says something straight out of a Wachowski Brother, like…
1. “The results are clear: Efexovir has no effect on the virus. The experiment failed.”
2. “Studies show Decretussin reduces coughing, though not significantly.”
3. “Bigpharmox is what’s making these cattle obese, I know it; now I just have to prove it!”
…they can always blame bad writing. And by bad, I mean “good, unless the viewer happens to understand what the writer doesn’t.” To wit,
1. the entire point of an experiment in science.
2. the significance of ‘significance’ in science.
3. the absolute precedence of evidence over knowledge in science.”
Nicholas,
You are out of luck. I believe the President has mentioned “Remdesivir” in a positive light several times. Therefore I predict that Remdesivir will receive the “HCQ” treatment by the US / Canadian media in any case.
None of this is about me.
“Is there another drug used to prevent it in places where malaria has become chloroquine-resistant?”
There are, usually lariam (mefloquine) or malarone (atovakvon/proguanine). Both have considerably worse side effects than chloroquine, especially mefloquine. Still, it’s better than malaria.
Willis,
Since your Coronavirus tab doesn’t allow comments, I’ll add a brief Sweden comment here. An indicator of things to come w/ Sweden is the ratio of the Serious, Critical cases compared with the number of deaths. For Sweden, that ratio is approaching 1 (not good). For the US, Spain, Italy, France, and the UK, the ratio is about .5 or less (not as bad). In my opinion, Sweden is not out of the woods yet.
It’s clear. The temperature in Sweden is not as high as in southern Europe. It is far from full spring.
Next-door neighbor Norway has better numbers than Sweden and the weather should be similar. Finland – not so much – but Finland like Sweden is an EU member.
Farmer,
Playing the Devil’s Advocate, perhaps Sweden intends to deal with its Muslim issues with the Wuhan Flu. I admit that I have no data on the demographics of the Swedish outbreak.
I recall Sweden having CV19 issues in no-go zones but can’t find the reference.
Covid-19 is very insidious. During the first five asymptomatic days, you can infect your interlocutors without your knowledge.
Therefore, medical personnel should receive plasma with antibodies prophylactically. Especially the personle after the age of 50.
Chloroquine should be administered no later than 6 days after the first symptoms. Once the lungs are already occupied, it may be ineffective.
It seems that chloroquine cannot be taken prophylactically.
Deadly coronavirus comes in three variants, researchers find
Types A, B and C are all derived from the pathogen first found in bats but have evolved in different ways, according to a report by British and German geneticists.
Findings show the virus has become well adapted to human transmission and mutates as it spreads, Chinese epidemiologist says.
https://www.scmp.com/news/china/science/article/3079491/deadly-coronavirus-comes-three-variants-researchers-find
From 0 to 24:00 on April 11, 31 provinces (autonomous regions and municipalities directly under the Central Government) and the Xinjiang Production and Construction Corps reported 99 newly diagnosed cases, of which 97 were imported cases and 2 were local cases (2 cases in Heilongjiang); none New death cases; 49 new suspected cases, all imported cases (43 cases in Shanghai, 3 cases in Heilongjiang, 2 cases in Inner Mongolia, and 1 case in Jilin).
And, you would expect anyone believe this report … why ?
Chinese doctors, and others who reported on the Covid early in the pandemic have been “disappeared” in a manner reminiscent of the Geheime Staats Polizei’s marking of N.N on a prisoners secret internal file … “N.N.” It meant ” Nacht und Nebel” The Night and Fog. The prisoner had disappeared into the Night and Fog. A condition everyone inside knew was incompatable with life. The manner of disappearance was deliberately contrived to terrorize the thus far unarrested populace.
To the surprise of the scientists, the T cell became a prey to the coronavirus in their experiment. They found a unique structure in the virus’s spike protein that appeared to have triggered the fusion of a viral envelope and cell membrane when they came into contact.
The virus’s genes then entered the T cell and took it hostage, disabling its function of protecting humans.
https://www.scmp.com/news/china/society/article/3079443/coronavirus-could-target-immune-system-targeting-protective
A combination of Hydroxychloroquine, Azithromycin and zinc supplements has been shown anecdotally to be the most effective cure and prophylactic against COVID19.
Hydroxychloroquine is one of only a few ionophores which can pass through cellular membranes and deliver zinc inside a cell. Zinc has been proven to stop COVID19 RNA from replicating, which is why it’s 70~90% effective. The key is to take these drugs before too much lung damage occurs.
Doctors who have prescribed Hydroxychloroquine from many decades for lupus and rheumatoid arthritis attest that it is very safe and only if 400mg/day is taken for over 5 years, are a few side Long-term effects like ventricular arrhythmia (1 in 1,000) and retinal damage (1%) observed. The chances of any of these side effects occurring over just 2 months of taking Hydroxychloroquine for COVID19 is nil…
Occasionally, patients have mild allergic reactions but it’s very rare and only suffer mild rashes and/or some vomiting/diarrhea.
The main reason Leftist media, political and bureaucrat hacks are so rabidly anti-Hydroxychloroquine is that Trump is for it; it’s just a glaring example of Trump Derangement Syndrome…
“Hydroxychloroquine is one of only a few ionophores which can pass through cellular membranes and deliver zinc inside a cell.”
Quercetin and EGCG are two others. No prescription needed.
Zinc ionophore activity of quercetin and epigallocatechin-gallate: from Hepa 1-6 cells to a liposome model
https://www.ncbi.nlm.nih.gov/pubmed/25050823
Icicles-san:
Hydroxychloroquine has been an extremely effective drug used around the world for 65 years for the treatment of malaria, lupus, rheumatoid arthritis and now the Wuhan flu.
I suppose some drug company could spend $2 billion to get FDA approval for Quercetin and EGCG if they like…..
No approval necessary. They are simply extracts from food sources. Widely available as dietary supplements.
Samurai
I’m curious about something. If the drug companies make so little money on HCQ, wouldn’t they have an incentive to make something that was more expensive, but worked better, for malaria, Lupus, and RA? What is holding them back?
I am counting a very short list of people here who have retained their rationality, and I am glad your are on it, Clyde.
You have always been one of the most lucid and well informed denizens of WUWT.
I think we are in more trouble than a virus and a disease, or an economic freeze.
Nicholas,
Thank you! I was beginning to feel that my comments were falling on deaf ears, or perhaps more appropriately, blind eyes.
I have long felt that most (if not all) humans are fundamentally irrational. They are only capable of rational behavior for short periods of time, in order to achieve their irrational goals. Most of the commenters here have reinforced that belief. There is a difference between being smart and being wise. While it is obvious that most commenters are smart and well-educated, I’m disappointed in the lack of wisdom demonstrated. However, that is why wisdom has been revered through the ages — it is so rare!
Is that you Tina?
Samurai: Even if quercetin had the potential to be effective drug – which is unlikely because it is quickly metabolized and all blood from intestines passes through the liver (the main site of metabolism) before traveling to the rest of the body – it isn’t a novel molecule that can be patented. Without the legal right to exclusive sale of a drug for 20 years that comes with a patent, no company is likely to spend the hundreds of millions it takes to prove a new medicine is safe and effective. Occasionally companies will isolate a natural product from plants and get a less-valuable patent on the use of that molecule for treating a particular disease, for example artemisin for malaria or for a process of obtaining the drug. Any company can manufacture and sell a drug once the patent expires, so a competitive marketplace often offers that drug for sale at a price that includes the cost of manufacture, distribution, sale and a competitive profit margin. While the sponsoring company holds a patent on the exclusive right to sell a drug (for whatever is left of its 20-patent life after 5-10+ years of development and clinical trials), the only competition comes from other drugs with the same mechanism of action. It is during this period that pharmaceutical companies recoup the cost of developing the drug and the cost of all of the drugs that failed to reach market and the 20% profit margin investors seem to demand for investing in such risky businesses. (30% for biotechnology drugs.) When the desired profit margin isn’t being obtained, you often see to companies merge, cut back on R&D and use the combined sale of existing drugs to restore their profit margin.
It is worth distinguishing between a medicine – which has been proven to be safe and effective (probability of null hypothesis of no effect less than 5%) usually in two large clinical trials – and medicinal use of non-drugs – which haven’t been proven safe or effective, and often contain an unknown amount of active ingredient(s) and/or toxins. Smoking tobacco is a dangerous way to treat yourself with nicotine, but highly rewarding since the drug reaches nicotine receptors your brain in seconds. Vaping was safer until they started adding a lot of flavors which decompose upon heating. Nicotine patches aren’t as rewarding since they deliver drug slowly through the skin. Oral bioavailability of nicotine is low, which is why some users chew tobacco for a long time and absorbed it in their mouth rather than swallow.
icisil
Stunning link!
Thanks’
Here is an article on Quercetin:
Nutritional Pharmacology March 21 2020 Combating COVID-19 with Zinc and Quercetin
There may be a one-off price to pay for not being instantly ready to respond to a pandemic – but that would dwarf into insignificance compared to the total price of living our lives and running our society and economy in a way that meant we were immediately ready for a pandemic/meteorite impact/any other conceivable major disaster.
In practice, given what was known at each stage, I do not think that we have put up a poor show. Deaths are not high. The people who have shown themselves to be the worst responders were unquestionably the journalists – which is a lot better for our society than if it had been, for instance, hospital administrators.
We now have to consider how to get out of lockdown. Just releasing people would run the risk of a second flare-up, so we need to have established some counter to this before ending it. Luckily, there are some helpful indications of advances which may help.
The delivery of a vaccine, which would enable lockdown release, is a year or so away. Even if accelerated testing is uniformly successful, the administrative process for getting most people in the country vaccinated would take many months on its own.
So I think that the most likely approach is a graduated release, maintaining the vulnerable in lockdown until a vaccine is developed while releasing the working people which the economy needs. This could be justified if Covid treatments were improved sufficiently to make the disease better able to be cured, and there are indicators of that on the horizon, viz:
1 – clinical trials of many drugs are now beginning, and several of these look promising.
2 – understanding of the mechanism of the virus attack is developing. In particular, hypotheses about its impact on blood cells seem to me to be well founded. If understanding is achieved here, better directed ICU treatment can immediately be implemented.
The timescale for the above advances could be measured in weeks. I anticipate that the lockdown could be lightened in a month or less if we get the developments in these fields that I am anticipating….