Swerd

Swerd

Audioholic Warlord
In one sense 8% vs 11.6% mortality [in the remdesivir trial] seems like a relatively small difference.
It was too small a difference.

Apparently, according to a story in yesterday's Washington Post, that trial as originally approved had patient deaths as it's primary endpoint. Time-to-recovery was one of the many secondary endpoints. In other words, the trial would be judged as successful or not based on comparing patient deaths in the remdesivir arm vs. the placebo arm, and the statistical significance of those numbers.

About 3 weeks before the announcement of the trial's results, the people running the trial at the NIAID saw that there were only about 95 deaths among both arms of the study. They didn't know which arm had how many deaths because the trial data was sealed, only that on both arms there was a total of 95 deaths. If the number of deaths on each arm were at all close to each other, n = 95 would mean the data could be inconclusive – no useful results! So, they quickly amended the trial, changing the primary endpoint to time-to-recovery.

They were right. The difference between 8% deaths on the remdesivir arm vs. 11.6% deaths on the placebo arm, where there was a total of 95 deaths among more than a total of 400 patients, was statistically insignificant (p=0.059), and would have made the trial an inconclusive bust. Because of their quick thinking, changing to time-to-recovery, saved things by producing useful results.

There were lots of critics, saying it was cheating to change the endpoint late in the game. They're wrong. It was fair because the data was still blinded at the time the amendment was filed. It was an example of how the NIAID saved their trial by acting fast. They clearly have a lot experience in doing this and deserve credit for the success.

With time, we'll see if remdesivir becomes a major anti-Covid-19 medication or not. It's already been given emergency approval by the FDA to treat only hospitalized Covid-19 patients. It's the only drug shown to have any kind of positive effect, which beats hydroxychloroquine, Lysol, or Chlorox by a country mile.
 
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mtrycrafts

mtrycrafts

Seriously, I have no life.
.... It's the only drug shown to have any kind of positive effect, which beats hydroxychloroquine, Lysol, or Chlorox by a country mile.
You mean the latter two had a null outcome? How large was the trial? ;) :D
 
M

Mr._Clark

Audioholic Samurai
It was too small a difference.

Apparently, according to a story in yesterday's Washington Post, that trial as originally approved had patients deaths as it's primary endpoint. Time-to-recovery was one of the many secondary endpoints. In other words, the trial would be judged as successful or not based on comparing patient deaths in the remdesivir arm vs. the placebo arm, and the statistical significance of those numbers.

About 3 weeks before the announcement of the trial's results, the people running the trial at the NIAID saw that there were only about 95 deaths among both arms of the study. They didn't know which arm had how many deaths because the trial data was sealed, only that on both arms there was a total of 95 deaths. If the number of deaths on each arm were at all close to eachother, n = 95 would mean the data could be inconclusive – no useful results! So they quickly filed amended the trial changing the primary endpoint to time-to-recovery.

They were right. The 8% vs. 11.6% mortality data was statistically insignificant (p=0.059) and would have made the trial an inconclusive bust. Because of their quick thinking, changing to time-to-recovery, saved things by producing useful results.

There were lots of critics, saying it was cheating to change the endpoint late in the game. They're wrong. It was fair because the data was still blinded at the time the amendment was filed. It was an example of how the NIAID saved their trial by acting fast. They clearly have a lot experience in doing this and deserve credit for the success.

With time, we'll see if remdesivir becomes a major anti-Covid-19 medication or not. It's already been given emergency approval by the FDA to treat only hospitalized Covid-19 patients. It's the only drug shown to have any kind of positive effect, which beats hydroxychloroquine, Lysol, or Chlorox by a country mile.
I would argue that we won't actually know if injecting Lysol or Chlorox is effective until we try it ! (that's a joke).

I've heard a number of experts recently state that they think monoclonal antibodies have the best chance of effectively treating COVID-19 to tide us over until a vaccine is developed.

I'm sure it's not that simple, but I find myself wondering why we can't just ramp up production on the two antibodies identified in the following paper and start treating patients? (that's a rhetorical question)

>>>In conclusion, we have successfully cloned two human blocking mAbs using SARS-CoV-2 RBD-specific memory B cells isolated from recovered COVID-19 patients. These two mAbs can specifically bind to SARS-CoV-2 RBD, block the interaction between SARS-CoV-2 RBD and hACE2 receptor, and lead to efficient neutralization of SARS-CoV-2 S protein pseudotyped virus infection. Such human anti-SARS-CoV-2 RBD-hACE2 blocking mAbs are first reported, and hold great promise to be exploited as specific prophylactic and therapeutic agents against ongoing SARS-CoV-2 pandemic.<<<

 
mtrycrafts

mtrycrafts

Seriously, I have no life.
I would argue that we won't actually know if injecting Lysol or Chlorox is effective until we try it ! (that's a joke).

...
I don't think it is a joke. ;)
I may have some volunteers to use in that trial.:D
 
Swerd

Swerd

Audioholic Warlord
I would argue that we won't actually know if injecting Lysol or Chlorox is effective until we try it ! (that's a joke).

I've heard a number of experts recently state that they think monoclonal antibodies have the best chance of effectively treating COVID-19 to tide us over until a vaccine is developed.

I'm sure it's not that simple, but I find myself wondering why we can't just ramp up production on the two antibodies identified in the following paper and start treating patients? (that's a rhetorical question)

>>>In conclusion, we have successfully cloned two human blocking mAbs using SARS-CoV-2 RBD-specific memory B cells isolated from recovered COVID-19 patients. These two mAbs can specifically bind to SARS-CoV-2 RBD, block the interaction between SARS-CoV-2 RBD and hACE2 receptor, and lead to efficient neutralization of SARS-CoV-2 S protein pseudotyped virus infection. Such human anti-SARS-CoV-2 RBD-hACE2 blocking mAbs are first reported, and hold great promise to be exploited as specific prophylactic and therapeutic agents against ongoing SARS-CoV-2 pandemic.<<<

It might be useful if development of effective vaccine(s) is delayed.

That type of treatment would still have to go through all the animal testing and clinical trials as would any other type of treatment.

Mass producing monoclonal antibodies is very expensive. Would drug companies want to invest in a product that would be used only until an effective vaccine is available? Probably not. On the other hand, if an effective vaccine cannot be made, monoclonal antibodies that blocked virus entry would be the best available treatment.
 
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Swerd

Swerd

Audioholic Warlord
Apparently they have started treating patients with antibodies:
They used antibodies directed against cytokine proteins (also known as interleukins) to dampen the inflammatory response run amok, the so-called cytokine storm. These antibodies were already approved treatments before the pandemic.

"Instead of attacking the virus, the monoclonal antibodies calm down the body's inflammatory response.​
"They're actually directed against certain parts of the immune system that contribute to this overactive response to the virus' invasion," Jeanfreau said."​

That other link to the paper in Nature was good. This link is to a local Faux News TV report. IMO, they're not such a good source.
 
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highfigh

highfigh

Seriously, I have no life.
Unreal! What the hell is going on there in that scull of his???
He must be outraged that he cannot blame or tie it to the the Chinese lab?
But ABC news has been saying that China lied about its severity......
 
T

TankTop5

Audioholic Field Marshall
But ABC news has been saying that China lied about its severity......
The idea that China didn’t lie is preposterous. If you’re arrested for a crime or you are sued you get a lawyer to represent your interests even if you’re guilty. China is on trial in the court of public opinion, guilty or not any information that comes out of China will be spun and misrepresented then spoon fed to the masses.
 
KEW

KEW

Audioholic Overlord
I would argue that we won't actually know if injecting Lysol or Chlorox is effective until we try it ! (that's a joke).
I think we do know that no one who drinks (or injects) Lysol or Chlorox will die from CoronaVirus, so it will effectively reduce the CoronaVirus mortality rate to zero!
Such is the genius of Trump!!!
If administered properly, bullets and knives can also be very effective!
 
Mikado463

Mikado463

Audioholic Spartan
I think we do know that no one who drinks (or injects) Lysol or Chlorox will die from CoronaVirus, so it will effectively reduce the CoronaVirus mortality rate to zero!
Such is the genius of Trump!!!
yeah but I like Biden's idea better........'Just buy a shotgun' !
 
KEW

KEW

Audioholic Overlord
yeah but I like Biden's idea better........'Just buy a shotgun' !
?
Are you saying that for you Biden suggesting a shotgun as a means of defending your home (instead of an assault rifle) somehow equates to Trump suggesting taking bleach internally?
Or are you saying that a shotgun is also an effective Trump-style "cure" for the virus (in which case I agree, but I don't understand why you would credit Biden)!?
 
Mikado463

Mikado463

Audioholic Spartan
Kurt, just adding another ounce or two of levity to your response, nothing more ! The just 'buy a shotgun' was in reference to the video (I posted it weeks ago) about Joe's rather dumb response in said video.
 
KEW

KEW

Audioholic Overlord
Kurt, just adding another ounce or two of levity to your response, nothing more ! The just 'buy a shotgun' was in reference to the video (I posted it weeks ago) about Joe's rather dumb response in said video.
2013, entirely different topic, pretty random - When you have to stretch that far, you tend not to have any grip left!
I can only dream of a reality where I need to go back more than a week to find an embarrassing statement from our current Whitehouse!
 
M

Mr._Clark

Audioholic Samurai
They used antibodies directed against cytokine proteins (also known as interleukins) to dampen the inflammatory response run amok, the so-called cytokine storm. These antibodies were already approved treatments before the pandemic.

"Instead of attacking the virus, the monoclonal antibodies calm down the body's inflammatory response.​
"They're actually directed against certain parts of the immune system that contribute to this overactive response to the virus' invasion," Jeanfreau said."​

That other link to the paper in Nature was good. This link is to a local Faux News TV report. IMO, they're not such a good source.
That's what I get for not reading the news blurb carefully.

I have not found a lot of information online about the difficulties in getting antibody drugs tested and in production, but the following article provides some information, albeit slightly dated:

>>>Scientists are scrambling to find powerful antibodies that can turn back the disease. But can they manufacture enough for everyone? . . .

There is intense pressure to accelerate the drugs’ development—to take corners at high speed, if not cut them altogether. But some experts say it’s not necessary to skip steps, something that could doom a drug later on. Instead, Ebola showed it’s partly a matter of spending 10 times the money to go twice as fast. “You don’t throw out the rules, but you shorten all the steps,” says Myron Levine, an infectious disease doctor at the University of Maryland, who has trained teams in Africa to run vaccine trials. “An accordion when extended is quite wide, but you push it together and it’s short. You don’t skip steps; you squeeze the accordion.” . . .

If the pandemic continues to grow, anyone who discovers a new treatment will be hard pressed to make enough of it. That’s especially true for antibodies.

During the Ebola trial, each subject got doses as high as 150 milligrams per kilo of body weight—or about 10 grams in all. If a covid-19 antibody is created, millions of people could need it. That means antibodies would need to be manufactured literally by the ton, in a process that involves skimming the molecules from tanks of living cells and drying them into a powder. But the biomanufacturing industry has never been asked to create that much of anything. If there’s an antibody Manhattan Project, it would be to build factories big enough for the job.

The largest biomanufacturing facilities in the world cost $1 billion to set up and have as much as 150,000 liters of broths bubbling at once. Carnley Norman, a vice president of manufacturing at KBI Biopharma, which produces antibodies, estimates that one such megafactory might be able to make enough antibody for a million people each year. But what if we needed to treat 10 or 100 million—and what if high doses of several different antibodies were required? At the high end, Norman’s calculation then becomes staggering: we’d need more than 300 such plants, more than exist in the world today. . . .

But all that’s only if we get a drug. And some believe the path to an antibody, like the path to a vaccine, is probably going to be difficult. “We have to worry about the efficacy and the safety, because this virus has unique features,” says Liusong Yin, who heads discovery of biological drugs at GenScript, a Chinese research company that has 50 people doing antibody screening. He says if the virus mutates, stopping it will demand more complex antibody cocktails that hit it in three or four places at once. And for severe cases, he worries, antibodies can sometimes make people sicker by contributing to a storm of immune activity. <<<

 
BoredSysAdmin

BoredSysAdmin

Audioholic Slumlord

Can someone smarter than me translate science to English please?
@Swerd @TLS Guy

Sent from my SM-G975U using Tapatalk
 
TLS Guy

TLS Guy

Seriously, I have no life.

Can someone smarter than me translate science to English please?
@Swerd @TLS Guy

Sent from my SM-G975U using Tapatalk
This is complicated, but a diagram can help. A virus needs a docking mechanism in order to gain entry to a target cell. In the case of Covid 19 the target cells are believed to be in the angiotensin II receptors. So an antibody which your immune system will produce at a time after exposure will block this docking mechanism and prevent entry of the virus into cells. If it happens quickly enough then you will have an asymptomatic infection. If on the other hand a swarm of viruses gain entry to your cells and high jack the mRNA to produce virus and destroy a large number of cells you will become ill, and either die, recover after your immune system produces sufficient antibody and your body go onto repair.

So the traditional means of creating immunity is to use the injection of a killed virus that can stimulate an immune response, or the use of a live but severely attenuated strain of the virus. The latter is the classic Edward Jenner approach to immunize against smallpox in 1795.

Now if you can manufacture an antibody against the correct antigen of a virus, then you can use that as a treatment to augment the body's immune system and shorten the recovery time. The problem is manufacture is difficult and tedious. That is the monoclonal antibody approach.

This diagram may help.



Now the Oxford group at the Jenner Institute, have a novel approach. They have taken an adenovirus, from monkeys that cause an asymptomatic infection in humans, and spliced in the DNA instructions to make antibody to hopefully. the correct antigen on Covid 19. So that when an individual is exposed to Covid 19 the instructions are already there to immediately start making neutralizing antibodies. This group have successfully used this to immunize individual against Middle Eastern Respiratory virus (MERS). This virus is another corona virus, and according to the Oxford group shares 80% of Covid 19"s structure.

They have already challenged monkeys that are our closest relatives they have given this vaccine to with a large quantity of Covid 19 virus and none have become sick.

Two weeks ago they took 1000 volunteers and injected half with this novel vaccine and half with a placebo. If the immunized do not become sick and show antibody to the Covid 19, then they have 6000 volunteers waiting to receive the vaccine. If that shows good results after six weeks, then they aim to produce a million doses right away and inject them. Professor Sarah Gilberts is on record saying that in her opinion chances of success is 80%. Astra Zeneka are gearing up to produce this at cost. Other sources are being looked for. Unfortunately no one is coming forward in the US.

This team is far ahead of anyone else. So it is high time for global backing so that this can be produced in vast quantities if successful. Boris Johnson is trying to organize a world wide coalition.

Imperial college has a similar messenger DNA approach under way, to direct muscle to produce antibody.

The US private equity company Moderna is using a novel messenger RNA approach and has started a small human trial. To me these three seem to be the most promising candidates at present. The Oxford group have to be considered front runners to solve this as they are the only one to have demonstrated efficacy of their method, with their success against MERS.

I have find the lack of world wide interest and excitement over this to be quite astonishing frankly. The odds of it working are a pretty good gamble, and with all the havoc the world should be betting massive funds on this now.

I do believe the answer to this will come from academia rather than big Pharma, the latter consistently demonstrating a severe lack of imagination on the whole. As far as I can tell they are pursuing traditional approaches which have been conspicuously unsuccessful against Corona viruses. Oxford is the better bet by far.
 
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