[PearlJam]

Originally Posted by proton

Sometimes, cures work because of other factors, of psychosomatic effects, belief, hope. That's why scientists use the randomised double blind methods.

Not sometimes, but a lot of times. We cannot under-estimate the placebo effect, which plays a significant role in healing many diseases. And, double blind tests have their own drawbacks. A simple google search will give the other view points. Unfortunately, we need to take the good with the bad, but we can't deny the downsides.

But, we're digressing. Since this thread is about Covid-19, we need to stick to that. A separate thread on medical discussions would be quite interesting.

Originally Posted by proton

Please answer this:

How is a cure, treatment or medicine passed in the scientific community?

You're trying to pin me down on something that both of us are not experts in. You're also assuming that everyone in the scientific community (which consists of big pharma, researchers funded by grants, watchdogs, etc) are acting selflessly in the best intentions and best interests of the humble patient, which is not the case. Otherwise, the current system wouldn't have been in such a crisis today.

As a layman, all I'm saying is that the current system is not in the pink of health (pun unintended). We all know either from personal experience, or that of close friends/relatives, the many side effects, drug reactions, and drug related fatalities. I'm saying this has be fixed, that's all.

Back to Covid-19 discussions going forward...

[proton]

Originally Posted by PearlJam

Back to Covid-19 discussions going forward...

All I'm saying is that the updates we have been receiving are ones with the state of the information as received. None has passed FDA or any scientifically recognised body's official, final, approval. These normally take years, as explained below.

Remdesivir was found to be effective initially. The virus adapted in 4 weeks, rendering the med ineffective. The updates received reflect this. There was no flip flop. It doesn't mean, however, that it was never effective.

Just to show that, sometimes, the cast iron 100 percent cure is not something that is reached over night.

[am1m]

Originally Posted by proton

Remdesivir was found to be effective initially. The virus adapted in 4 weeks, rendering the med ineffective.

Is that what happened? I know that some studies showed it was ineffective and some patient experiences showed it was helpful. Which I guess is normal since we are really still in the early stages of this pandemic and understanding of the virus. But I can't seem to find any source that talks about the virus adapting to the drug.

[proton]

Originally Posted by am1m

Is that what happened? I know that some studies showed it was ineffective and some patient experiences showed it was helpful. Which I guess is normal since we are really still in the early stages of this pandemic and understanding of the virus. But I can't seem to find any source that talks about the virus adapting to the drug.

This is from March 2020. There is a more recent post referring to the virus taking 4 weeks to render remdesivir ineffective in Brazil. I'm trying to locate it. Everything this guy said would happen has happened, in India. The thread is a great resource to facing the virus, and quite an eye opener. Apparently, we paid him big bucks to consult on the virus, but our country ignored his recommendations. His colleagues, Jennifer and Rob, broke the rules of the organisation banning them from working in India, and went to the Dharavi slums, where they organised the anti Covid-19 effort, much praised by WHO.

Quote
If you read about Remdesivir, you will find it showed 100 percent success with Ebola and Marburg initially, but eventually it was rendered useless.
In very simple terms, single stranded RNA virus is impossible to contain with single anti viral agent.
Zaire ebola took less than 48 hours to bypass it by simply making the host cell produce RNA replicase in abundance.
We desperately need a replicase inhibitor. Once we use both together, this damn virus will possibly go away.

https://techenclave.com/threads/what...2#post-2198506

[am1m]

Originally Posted by proton

The thread is a great resource to facing the virus, and quite an eye opener.

With respect, I know you have been quoting from that forum on and off and from your previous posts, I know you quote them in good faith. But I have to point out that an anonymous source who tangentially mostly takes off on the government every chance he gets, quite often it has to be said unnecessarily (I did read through his posts on that forum back when you quoted them in the 'lockdown' thread) doesn't really inspire much confidence. And only adds to the impression that this thread on this forum is just about government bashing.

I'm sure you have good reason to put stock in that thread, but personally on an issue like the virus overcoming a drug in 4 weeks, I would rather wait for a published study in an established medical journal.

[venkyhere]

Blind men describing a marauding elephant, and based on this description, are forced by overlords to design a safari suit for it within 2 days - that's covid19. I don't think there will be a stable vaccine20 or even vaccine21; may be vaccine22.

Until then, stay alert and keep looking over our backs whether we are becoming too complacent and are wandering into the elephants path.

[proton]

Originally Posted by am1m

With respect, I know you have been quoting from that forum on and off and from your previous posts, I know you quote them in good faith. But I have to point out that an anonymous source who tangentially mostly takes off on the government every chance he gets, quite often it has to be said unnecessarily (I did read through his posts on that forum back when you quoted them in the 'lockdown' thread) doesn't really inspire much confidence. And only adds to the impression that this thread on this forum is just about government bashing.

I'm sure you have good reason to put stock in that thread, but personally on an issue like the virus overcoming a drug in 4 weeks, I would rather wait for a published study in an established medical journal.

I think it's well known that during epidemics, governments request media to be cautious about what they put online. Now we also know that progressive organisations have in turn requested governments to be honest in informing their populations, to improve the trust that exists between the two. Two weeks back we received just such a request from the UN.

So what side do you think our government is leaning to, and do you think it is correct, that they be given powers with no checks and balances, to decide how and why and which news, which can control panic or provide life saving info, depending on the maturity of the population, should be regulated?

If there is some control, which is the best source of getting information that protects you, that you think over rides what others think is good for the population?

I have to tell you that I am constantly in contact with people in media (my nephew has unfiltered info from all the important newsfeeds, he is an anchor on Sing TV, probably the only one from India, and his info is pretty grim, coinciding with the link I provided).

These are the factors I have to take into consideration, considering that world leaders like Trump have said they communicated the virus was like a mild flu, just to prevent panic. Who is he to decide? What he said led to wrong behaviour from large sections of the population, who never took precautions because of what he said, but also led to some looking at his past record and chosing to be cynical.

I believe there is going to be closer looks at laws worldwide, reformation geared towards preventing people in responsible positions from creating fake information, just like social media is taking action against fake info, within their powers in their respective domains. Trump would be arrested for willful endangerment of lives, if the laws were enacted with retrospective effect.

End of rant!

[Zen2001]

At the end of it all comes the issue of accountability and responsibility. This is always a retrospective analysis so don't say that we now have the advantage of hindsight, which our leaders / policymakers did not have 6-8 months ago. It with have been called foresight then, which they lacked back then and even today is quite lacking (other than in areas of protecting their own vested interests - see all the election rallies for luring the votebank). The government's pandemic response should be critically audited and critical junctures identifed and made adequately public - policy decisions where things went wrong and how a different approach would have been better, based on clear epidemiologic and mathematical modelling that is proven to be predictable. Why did they apply Cambridge model to our demography? It's like running your vehicle on the wrong fuel and engine oil. This is not the last disease we have seen and who would want this situation to repeat again? Only politicians, obviously. Not even doctors and hospitals.

[Zen2001]

Originally Posted by proton

.
Remdesivir was found to be effective initially. The virus adapted in 4 weeks, rendering the med ineffective. The updates received reflect this. There was no flip flop. It doesn't mean, however, that it was never effective.

Really? How big was this study? Was it blinded? Was it open ended? Was it a crossover? Can you post the scientific peer reviewed publication of the same? I'm asking because even Gilead never claimed that the drug would affect mortality. That has not changed even today. And lastly, the drug has got nothing to do with the virus (or its adaptability) - it just had an immunomodulatory action which was used purely on observations of high IL-6, CRP, Ferritin, Procalcitonin, which are surrogates of an accelerated immune response, cargo called SIRS (systemic inflammatory response syndrome) which progresses eventually to ARDS (in the lungs) and eventually MODS (multiple organ dysfunction syndrome) leading to death. This same process happens after any major insult, injury, burns, infections and is not just related to Covid19. Also, the D614G mutation of the virus identified in April-May in many countries only affected the infectivity, not the severity. These are the facts. So far, other than corticosteroids (given any the right time during the illness) nothing else has proven significantly effective (other than in isolated/clustered reports, which may be inclined toward bias).

[proton]

Originally Posted by Zen2001

Really? How big was this study? Was it blinded? Was it open ended? Was it a crossover? Can you post the scientific peer reviewed publication of the same? I'm asking because even Gilead never claimed that the drug would affect mortality. That has not changed even today. And lastly, the drug has got nothing to do with the virus (or its adaptability) - it just had an immunomodulatory action which was used purely on observations of high IL-6, CRP, Ferritin, Procalcitonin, which are surrogates of an accelerated immune response, cargo called SIRS (systemic inflammatory response syndrome) which progresses eventually to ARDS (in the lungs) and eventually MODS (multiple organ dysfunction syndrome) leading to death. This same process happens after any major insult, injury, burns, infections and is not just related to Covid19. Also, the D614G mutation of the virus identified in April-May in many countries only affected the infectivity, not the severity. These are the facts. So far, other than corticosteroids (given any the right time during the illness) nothing else has proven significantly effective (other than in isolated/clustered reports, which may be inclined toward bias).

I have already stated that no findings have been finalised, considering the early stage in the experience that we find ourselves in. However, that doesn't mean no treatments are not being TRIED.

As a potential end user, however, and as someone feeling the need not to park my brains outside before I enter the hospital, I must at least know the usefulness of a treatment before allowing it to be used on me, in case I fall victim to the virus. Right now, if I were to be asked if I wanted to be administered remdesivir, I know enough to refuse it. In my situation, that's what counts, right?

The details of how it works and how it has stopped working, though I can provide it, albeit an empirical report, really doesn't matter does it? If someone on this thread wanted a peer reviewed, double blind verified study, it's not available at this stage, right?


I wanted to give that empirical reference, because it made sense, but others have already advised against giving these uncurated citations. However, some information is better than nothing, so here goes, and I hope no one ever needs to use it, but if the occasion arises, I also hope it helps in making an informed decision (that's another Pandora's Box in the litigation scene, I know).

Quote
It is a RNA virus which uses reverse transcriptase to convert the RNA to DNA which integrates with human DNA and starts replicating, eventually the host cell dies and thousands of virions get ready to attack thousands more cells.

https://techenclave.com/threads/what...9/post-2196696

From what I can understand from different posts, HCQS, Remdesivir all act in preventing the virus from breaking out from cells by increasing the zinc barriers they form in the cell walls. However, the virus increases its replicating capacity and overwhelms these barriers, rendering these drugs useless. Unless a replicasing inhibitor is found, all the future treatments that focus on preventing cell barrier improvement, will also prove to become ineffective.

Please correct me if I'm wrong in my layman understanding of the mechanics of the process. I'm not going to protest any injury to my ego: it's more important to get the right information across to help in reaching right decisions. Thanks in advance.

[Zen2001]

Originally Posted by proton

I have already stated that no findings have been finalised, considering the early stage in the experience that we find ourselves in. However, that doesn't mean no treatments are not being TRIED.

Not entirely true. The findings with Remdesivir have been more than finalised by now with evidence that it merely reduced hospital stay by 3 to 4 days as compared with "standard of care" with no statistically significant impact on mortality. At this point of time, I'm more aware of any NEW treatment that is currently being tried.

Originally Posted by proton

As a potential end user, however, and as someone feeling the need not to park my brains outside before I enter the hospital, I must at least know the usefulness of a treatment before allowing it to be used on me, in case I fall victim to the virus. Right now, if I were to be asked if I wanted to be administered remdesivir, I know enough to refuse it. In my situation, that's what counts, right?

Let's assume you don't park your brains outside the hospital, but do you study the aetiology, pathophysiology, clinical presentations, differential diagnosis, diagnostic modalities, drug pharmacokinetics and pharmacodynamics, types of adverse drug reactions (drug alone, drug-drug, drug-food), complications, prognosis and therapeutic cure rates before accepting any treatment? Let's say even if you did, that's your personal situation - it cannot be applied on a large scale, let alone that of a pandemic.

Originally Posted by proton

The details of how it works and how it has stopped working, though I can provide it, albeit an empirical report, really doesn't matter does it? If someone on this thread wanted a peer reviewed, double blind verified study, it's not available at this stage, right?

Please provide a scientific supported (even if hypothesised) report of the same. Yes, because it does matter. As far as your concern of trials goes, read on.

On February 5, 2020, a phase 3 randomized, quadruple-blind, placebo-controlled clinical trial was registered at Capital Medical University, with the goal to determine safety and efficacy of remdesivir in patients with mild to moderate SARS-CoV-2 infection (NCT04252664, since suspended).

A day later, a second trial (NCT04257656, since terminated) was registered at the same location, focused on patients with advanced COVID-19 respiratory disease.

The National Institute of Allergies and Infectious Diseases (NIAID), NIH initiated the Adaptive COVID-19 Treatment Trial (ACTT), a double-blind, randomized, placebo-controlled phase 3 trial to evaluate the safety and efficacy of remdesivir compared with a remdesivir placebo-control (NCT04280705). NIAID developed this study in part based on the existing Chinese clinical trials in addition to consulting with the WHO.

Gilead Sciences initiated two clinical trials that began in mid-March, comparing remdesivir to standard of care in patients with moderate or severe coronavirus disease (COVID-19) in an open-label, randomized trial, NCT04292899. This trial will explore the safety and efficacy of remdesivir in combination with standard of care to compare study arms of 5- or 10-day remdesivir dosing on the primary outcome of fever and oxygen saturation. NCT04292730 maintains three study arms to compare remdesivir provided over 5 or 10 days, to standard of care alone, with the primary outcome being the proportion of patients discharged by the 14th day. (This was changed after they couldn't get their initial primary outcome, mortality, as desired)

The WHO announced the SOLIDARITY clinical trial, a four-arm trial comparing remdesivir, lopinavir/ritonavir, lopinavir/ritonavir with interferon-β1a, and chloroquine or hydroxychloroquine (ISRCTN83971151). With the goal of reducing trial design time and start-up, the WHO seeks to rapidly facilitate comparison of treatments on a worldwide scale. Data will be analyzed on an interim basis by an independent group of experts, the Global Data and Safety Monitoring Committee, enabling the modification of study design if particular treatments show early promise.

This trial has largely proven the ineffectiveness of Remdesivir (across 70 participant countries). I don't know what more evidence you are looking for.

I have posted an image of some of the trials initiated worldwide - may not include then all though.

Originally Posted by proton

I
I wanted to give that empirical reference, because it made sense, but others have already advised against giving these uncurated citations. However, some information is better than nothing, so here goes, and I hope no one ever needs to use it, but if the occasion arises, I also hope it helps in making an informed decision (that's another Pandora's Box in the litigation scene, I know).

That "empirical" reference actually makes no sense, because the writer has not understood the mode of action of Remdesivir. It DOES INHIBIT the RNA dependant RNA polymerase, which he seems to be looking for! While something is better than nothing as a general rule, half baked and half true (or maybe even fake) information is worse than no information at all.

Originally Posted by proton

Quote
It is a RNA virus which uses reverse transcriptase to convert the RNA to DNA which integrates with human DNA and starts replicating, eventually the host cell dies and thousands of virions get ready to attack thousands more cells.
https://techenclave.com/threads/what...9/post-2196696
From what I can understand from different posts, HCQS, Remdesivir all act in preventing the virus from breaking out from cells by increasing the zinc barriers they form in the cell walls. However, the virus increases its replicating capacity and overwhelms these barriers, rendering these drugs useless. Unless a replicasing inhibitor is found, all the future treatments that focus on preventing cell barrier improvement, will also prove to become ineffective.
Please correct me if I'm wrong in my layman understanding of the mechanics of the process. I'm not going to protest any injury to my ego: it's more important to get the right information.

Viral genome replication is mediated by the viral replication complex, which includes an RNA-dependent RNA polymerase (RdRp), helicase, exonucleaseN, and other accessory proteins. Subsequent assembly of viral nucleocapsids from the packaged viral genomes and translated viral structural proteins occurs at the endoplasmic reticulum-Golgi intermediate compartment, with infectious virions then released from the cell through exocytosis. Viral replication by "reverse transcription" is nothing new and we have several reverse transcriptase inhibitors that have been spectacular in success against HIV, Hep B Hep C, which use the same process for replication. So, the "replicase inhibitors" you are looking for are nothing new.

Remdesivir’s antiviral activity, sterically interacting with the viral RdRp to induce delayed chain termination, has been demonstrated in vitro against multiple coronaviruses (SARS, MERS, contemporary human CoV and bat-CoVs). However, in vitro (conducted on cell cultures in labs) results are not always reproducible in vivo (inside the human body). There is no mention about any zinc barriers in literature. I hope that's clear now.

Now look at this. Favipiravir is a selective and potent inhibitor of influenza viral RNA polymerase, and effective against all subtypes and strains of influenza viruses including ones sensitive or resistant to marketed neuraminidase and M2 inhibitors. Favipiravir demonstrated anti-viral activities against other RNA viruses. The SARS-CoV RdRp complex is at least 10-fold more active than any other viral RdRp known. It possesses both unusually high nucleotide incorporation rates and high-error rates allowing facile insertion of Favipiravir into viral RNA, provoking C-to-U and G-to-A transitions in the already low cytosine content SARS-CoV-2 genome.

When this drug, with a similar mode of action, is available in an oral form at cheaper cost, why is it all about Remdesivir? After all, this drug has also received FDA EUA and DGCA approval for clinical use in Covid 19. Think about it.

[proton]

Originally Posted by Zen2001

This trial has largely proven the ineffectiveness of Remdesivir (across 70 participant countries). I don't know what more evidence you are looking for.

Thanks! However, the only benefit that I see is that it reduces my hospital stay by a few days. I don't see that as a compelling reason to take it, as against the potential side effects that some have reported it causes.

Maybe I'm stupid?

Quote
Remdesivir side effects
Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Some side effects may occur during the injection. Tell your caregiver right away if you have:

nausea, vomiting;

chills or shivering;

increased sweating; or

a light-headed feeling, like you might pass out;

Common side effects may include:

abnormal liver function tests; or

pain, swelling, bruising, or bleeding around the IV needle.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

See also:
Remdesivir side effects (in more detail)

https://www.drugs.com/mtm/remdesivir.html

[Gsynch]

While the consensus of the thread is that "Lockdowns are ineffective and local government (Indian govt) have used it because of lack of expertise and vision to fight pandemic", developed countries with much greater resources at their disposal are seen enforcing the second wave of lockdown.

https://timesofindia.indiatimes.com/...w/78923165.cms

"We are all in the same position: overrun by a second wave which we know will be harder, more deadly than the first, he said. "I have decided that we need to return to the lockdown which stopped the virus."

As a person with a non-medical background, this baffles me. Lockdowns are working or the world over this strategy has been ineffective?

[Zen2001]

Originally Posted by proton

Thanks! However, the only benefit that I see is that it reduces my hospital stay by a few days. I don't see that as a compelling reason to take it, as against the potential side effects that some have reported it causes.
See also:
Remdesivir side effects (in more detail)

https://www.drugs.com/mtm/remdesivir.html

Looks like they forgot "reactivation of latent TB" as one of the side effects. Imagine what that spells for a country like India (and many in Africa, S.America). Doom.

Even then, overlooking safety or severe side effects, was there compelling evidence of EFFICACY? Read here -

https://science.thewire.in/health/cd...ab-itolizumab/

[vivek95]

I am very busy with my Covid icu duties but would like to say just one thing that don't fall prey to this horrible claims that the second wave is deadlier than the first. What sick minded people we have in this world, seriously !!

Stay calm, things are definitely better and under control. Current fatality rate even in EU is no where close to how alarming it had been way back in February. Mere rise in infections doesn't mean people are dying right left and centre again. Follow the authentic news sources. This world has gone crazy, to hell with covid !!!!