I am missing Fujifilm's Avigan/Favipiravir here - Chinese reported success using it:
"On 17 March 2020, Chinese officials suggested that Favipiravir seemed to be effective in treating COVID-19 in Wuhan and Shenzhen.[31][32][33]
A study on 80 patients comparing it to lopinavir/ritonavir found that it significantly reduced viral clearance time to 4 days, compared to 11 for the control group, and that 91.43% of patients had improved CT scans with few side effects."
Stage of disease also is important. In the first symptomatic stage, makes sense to try antivirals and HCQ to reduce or eliminate the virus, and prevent a cascade into the next stage. The problematic second stage - ARDS, a subset of patients who really go critical, seems to call for different approach because at that time, it’s the cytokine storm and our own immune reaction killing us.
Can anyone comment about the worldwide production capacity and possible lower price limits for these drugs?
It should be possible to supply a large part of the worlds population with (hydroxy)chloroquinine if that is deemed a solution, but the others seem less ideal candidates for that, or am I wrong?
What I can personally comment on is that if people go on with hoarding on quinine derivatives, we're gonna have a massive problem whether it's found effective or not.
The hoarding is even happening among my lesser scientifically-reasonable md colleagues. This has to stop. Now.
Before the virus, the global supply of Remdesivir was only enough to treat a few hundred people. Chloroquine and Hydroxychloroquine are apparently very easy to make, and can be scaled up very quickly. Not sure about the last two.
Regardless, WHO should be doing trials on more over-the-counter products. It's dumb that they put out a statement warning people that there was no evidence that Garlic could be used as an antiviral, despite the fact that literally two days ago the FDA granted emergency expanded access for some multi-million dollar inhaled nitric oxide device based on the fact that nitric oxide has been shown to block the replication of SARS-CoV in vitro. (Guess the mechanism of action by which eating raw garlic nearly instantly lowers your blood pressure.)
Anyone knows why serum is not sufficient to completely solve all our issues? I applaud this trial but this confuses me. It seems like we already have the capacity to do this on large scale, it's considered very safe and as far as I understand is highly effective. There was an article about it here a few days back, but besides that I don't hear much about it in the general discussion, why?
It can’t be done effectively during exponential growth at the current rate: there simply aren’t enough identified recovered patients to supply serum to the currently sick patients. If the exponential rate decreases a bit, maybe.
FWIW, it seems at least plausible to me that a recovered patient who was treated with serum may not generate as many protective antibodies as a naturally recovered patient. For example, Rh antibodies are used during pregnancy specifically to prevent an immune response. I don’t know if this would apply to COVID-19 or if giving serum only after symptoms become severe would prevent this outcome.
Not a doctor, but AFAIK its not considered safe enough. There are quite a few possible side-effects from using some of the mentioned medication, ranging from diarrhea to QT interval changes that could induce cardiac arrest.
One thing I couldn't find a source for is how many donors could potentially help how many people. Is it 1 to 1? 1 donor can help multiple people? Or one patient needs the amount of multiple donors?
I think trials for this are beginning - I suspect it would have been a hard thing to include in the WHO trial, as a hospital needs to be fairly sophisticated to be able to coordinate plasma retrieval and cleaning locally (vs buying RBCs from a local supplier).
I’m curious /excited to rare how this dynamic changes once we get serological tests online. Maybe all of the mild cases amongst youth can give enough serum to treat the harder hit individuals.
> It’s not a vaccine. Think about it as the administration of a protein, it’s a liquid that is given to people that gives them immunity.
> Right. Because the vaccine would provoke the recipient’s antibodies. You'll have the antibodies, but they won't be your antibodies—though it'll do the same thing.
The difference of serum to vaccination is that any resistence/immunity gained from serum will only last until the antibodies are eliminated from your blood.
A vaccine triggers an active immune response. That includes the differentiation of aptly-called "memory" B cells. Those can lie dormant for decades and spring into action when needed.
Its interesting to note they did not mention antibiotics as something that was being tested. I know for a fact that a major bay area hospital is treating covid-19 patients with a course of antibiotics(unsure which type), which is strange as its a virus. The nurse I know said they are seeing good results, the antibiotics are administered right away(they didn't say if anything else is administered) and 5 of 6 patients are being sent home with none coming back with worse symptoms. The sample size is small, maybe 30-40 and I wonder if these patients are already healthy enough that the virus is not affecting them greatly. It looks like other countries are looking into it as well:
It is almost certainly azithromycin. Interestingly, it's antiviral effects have be previously studied. However, people aren't really happy with the lack of error bars on that (French Study) chart or the small sample size. Studies are double blind for a reason.
... and most anything that Derek Lowe has to say about small molecule drugs. He's apparently had a bit of time at home recently to blog more, and is rather focused currently on Corona virus.
One theory I've heard is that it is not the virus itself that kills you, but your immune system overreaction causing secondary damage which leads to infections. So the antibiotic might be aimed at that part? Just a guess.
They are probably put on antibiotics when they are intubated, to prevent:
Ventilator-associated pneumonia (VAP) is a type of lung infection that occurs in people who are on mechanical ventilation breathing machines in hospitals. ... Between 8 and 28% of patients receiving mechanical ventilation are affected by VAP
this information might become relevant if anybody dear to you is hospitalized with Corona virus related symptoms: The WHO is running a randomized trial to check the effect of existing medications:
"Enrolling subjects in SOLIDARITY will be easy. When a person with a confirmed case of COVID-19 is deemed eligible, the physician can enter the patient’s data into a WHO website, including any underlying condition that could change the course of the disease, such as diabetes or HIV infection. The participant has to sign an informed consent form that is scanned and sent to WHO electronically. After the physician states which drugs are available at his or her hospital, the website will randomize the patient to one of the drugs available or to the local standard care for COVID-19."
UCSF had a great video conference call with several of their experts essentially covering these drugs and the two different stages of the disease.
I highly recommend watching the first half at least. https://youtu.be/bt-BzEve46Y
What took so long? It's clear you've never been involved in clinical trials. This is blisteringly fast. These things usually take many months of planning and review.
Chloroquine has a host of potential, damaging side-effects. It's reasonable to hold it to a higher standard when the risks of taking it are also higher.
The WHO usually isn't in the business of sponsoring trials. The development of a single master protocol takes time, especially for one as large as this, and pulling one together within just a few weeks is already quite incredible, given the many, many partners that have to be involved, and how carefully you have to design it to balance a bunch of different factors.
Multi armed bandit methods work best with immediate success-fail metrics. This one has time delays.
An example of how machine learning goes wrong is if a treatment slows down the progression but increases the death rate. Given exponential ramp up in the incoming cases, it will look good until the final horrifying numbers are in. You need to slice and dice the numbers by cohort to detect/react to this.
Is the expectation that SARS-CoV-2 will become a seasonal virus, permanently with us, like the other 4 coronaviridae (which we don't have a vaccine for)?
It seems that those keep coming back each year either because they mutate, or the antibodies produced by our bodies are no longer produced/effective after a year or so.
So even if we had a vaccine for SARS-CoV-2, would it lose its' potency after a year, and people need annual booster shots? Or would the virus mutate so that the specific vaccine no longer works?
Also, is the expectation that the mortality rate of SARS-CoV-2 will reduce over time because of evolutionary pressure? Is that really the case, given that much of the spreading happens in the first 1-2 weeks, before the host is potentially dead?
Forbes: Coronavirus Patient Dodged A Bullet With Hydroxychloroquine.
Mar 22, 2020,01:43pm EDT
"Two scientists at major university centers reviewed the French trial for me. They agreed, separately, that while the study is preliminary, small, and not without flaws, its findings were strong enough, given the drugs’ known safety records, to guide treatment decisions in a crisis.
“Despite the limitations of this study, in the absence of any effective treatment, in this urgent situation, this Plaquenil and Azithromycin combination therapy should be given to patients with COVID-19 as a treatment option,” Ying Zhang, a professor of microbiology at Johns Hopkins Bloomberg School of Public Health, wrote in an email. “For now, there is no time to wait."
Brian Fallon, a research scientist and clinical trials investigator at the Columbia University Irving Medical Center, agreed on the study’s overall merit despite the patients who dropped out. After analyzing the data and counting all six dropouts as treatment failures, he said the overall rate of improvement was still statistically significant for the entire group, though not for the hydroxychloroquine group alone."
[+] [-] bitL|6 years ago|reply
"On 17 March 2020, Chinese officials suggested that Favipiravir seemed to be effective in treating COVID-19 in Wuhan and Shenzhen.[31][32][33]
A study on 80 patients comparing it to lopinavir/ritonavir found that it significantly reduced viral clearance time to 4 days, compared to 11 for the control group, and that 91.43% of patients had improved CT scans with few side effects."
https://en.wikipedia.org/wiki/Favipiravir
[+] [-] DocSavage|6 years ago|reply
[+] [-] ArnoVW|6 years ago|reply
My understanding is that most deaths are in the elderly, and that those deaths are due to pneumonia.
[+] [-] vhvjkyhkogvv|6 years ago|reply
[+] [-] getrealhonest|6 years ago|reply
[deleted]
[+] [-] ignoramous|6 years ago|reply
1. Remdesivir (Ebola drug).
2. Chroloquine and Hydroxychroloquine (Malaria drug).
3. Ritonavir/lopinavir (AIDS drug).
4. Ritonavir/lopinavir + interferon beta (virus signaling protein).
[+] [-] tosser0001|6 years ago|reply
https://books.google.com/ngrams/graph?content=interferon
[+] [-] jokowueu|6 years ago|reply
[+] [-] jaynetics|6 years ago|reply
It should be possible to supply a large part of the worlds population with (hydroxy)chloroquinine if that is deemed a solution, but the others seem less ideal candidates for that, or am I wrong?
[+] [-] rscho|6 years ago|reply
The hoarding is even happening among my lesser scientifically-reasonable md colleagues. This has to stop. Now.
[+] [-] Alex3917|6 years ago|reply
Regardless, WHO should be doing trials on more over-the-counter products. It's dumb that they put out a statement warning people that there was no evidence that Garlic could be used as an antiviral, despite the fact that literally two days ago the FDA granted emergency expanded access for some multi-million dollar inhaled nitric oxide device based on the fact that nitric oxide has been shown to block the replication of SARS-CoV in vitro. (Guess the mechanism of action by which eating raw garlic nearly instantly lowers your blood pressure.)
Sources here: https://www.reddit.com/r/covid19stack/
[+] [-] nil-sec|6 years ago|reply
[+] [-] amluto|6 years ago|reply
FWIW, it seems at least plausible to me that a recovered patient who was treated with serum may not generate as many protective antibodies as a naturally recovered patient. For example, Rh antibodies are used during pregnancy specifically to prevent an immune response. I don’t know if this would apply to COVID-19 or if giving serum only after symptoms become severe would prevent this outcome.
[+] [-] crypt1d|6 years ago|reply
[+] [-] raverbashing|6 years ago|reply
[+] [-] ejstronge|6 years ago|reply
I’m curious /excited to rare how this dynamic changes once we get serological tests online. Maybe all of the mild cases amongst youth can give enough serum to treat the harder hit individuals.
Here’s a recent discussion about serum:
https://www.globalhealthnow.org/2020-03/covid-19s-stop-gap-s...
And the linked study:
https://www.jci.org/articles/view/138003
[+] [-] rscho|6 years ago|reply
And many more reasons...
[+] [-] dforrestwilson|6 years ago|reply
It’s helpful in the short term, but not effective for longer than a few weeks apparently. Also there may be scaling issues?
[+] [-] f_allwein|6 years ago|reply
> It’s not a vaccine. Think about it as the administration of a protein, it’s a liquid that is given to people that gives them immunity.
> Right. Because the vaccine would provoke the recipient’s antibodies. You'll have the antibodies, but they won't be your antibodies—though it'll do the same thing.
[+] [-] IAmEveryone|6 years ago|reply
A vaccine triggers an active immune response. That includes the differentiation of aptly-called "memory" B cells. Those can lie dormant for decades and spring into action when needed.
[+] [-] subsubzero|6 years ago|reply
https://techcrunch.com/2020/03/19/french-study-finds-anti-ma...
[+] [-] kurthr|6 years ago|reply
I would recommend this post: https://blogs.sciencemag.org/pipeline/archives/2020/03/19/co...
... and most anything that Derek Lowe has to say about small molecule drugs. He's apparently had a bit of time at home recently to blog more, and is rather focused currently on Corona virus.
[+] [-] rossdavidh|6 years ago|reply
[+] [-] hjlsertert|6 years ago|reply
Ventilator-associated pneumonia (VAP) is a type of lung infection that occurs in people who are on mechanical ventilation breathing machines in hospitals. ... Between 8 and 28% of patients receiving mechanical ventilation are affected by VAP
https://en.wikipedia.org/wiki/Ventilator-associated_pneumoni...
[+] [-] MichaelMoser123|6 years ago|reply
"Enrolling subjects in SOLIDARITY will be easy. When a person with a confirmed case of COVID-19 is deemed eligible, the physician can enter the patient’s data into a WHO website, including any underlying condition that could change the course of the disease, such as diabetes or HIV infection. The participant has to sign an informed consent form that is scanned and sent to WHO electronically. After the physician states which drugs are available at his or her hospital, the website will randomize the patient to one of the drugs available or to the local standard care for COVID-19."
[+] [-] haybanusa|6 years ago|reply
[+] [-] salimmadjd|6 years ago|reply
[+] [-] pbreit|6 years ago|reply
Still seems chloroquine is required to meet a higher bar than the others which continues to be odd.
[+] [-] onychomys|6 years ago|reply
[+] [-] Filligree|6 years ago|reply
[+] [-] endorphone|6 years ago|reply
I mean...it seems likely that some of the boosters who have been astroturfing it do actually have a stake.
[+] [-] lekanwang|6 years ago|reply
[+] [-] tom_mellior|6 years ago|reply
Does the article say anything about different bars for the different treatments? I must have missed that. What are you referring to?
[+] [-] rscho|6 years ago|reply
[deleted]
[+] [-] vhvjkyhkogvv|6 years ago|reply
[+] [-] btilly|6 years ago|reply
An example of how machine learning goes wrong is if a treatment slows down the progression but increases the death rate. Given exponential ramp up in the incoming cases, it will look good until the final horrifying numbers are in. You need to slice and dice the numbers by cohort to detect/react to this.
[+] [-] ignoramous|6 years ago|reply
[+] [-] flir|6 years ago|reply
[+] [-] dharma1|6 years ago|reply
https://www.cdc.gov/coronavirus/general-information.html
It seems that those keep coming back each year either because they mutate, or the antibodies produced by our bodies are no longer produced/effective after a year or so.
So even if we had a vaccine for SARS-CoV-2, would it lose its' potency after a year, and people need annual booster shots? Or would the virus mutate so that the specific vaccine no longer works?
Also, is the expectation that the mortality rate of SARS-CoV-2 will reduce over time because of evolutionary pressure? Is that really the case, given that much of the spreading happens in the first 1-2 weeks, before the host is potentially dead?
[+] [-] electriclove|6 years ago|reply
[+] [-] bsaul|6 years ago|reply
[+] [-] ggm|6 years ago|reply
[+] [-] drited|6 years ago|reply
[+] [-] primrose|6 years ago|reply
[+] [-] teddyvangogh|6 years ago|reply
Mar 22, 2020,01:43pm EDT
"Two scientists at major university centers reviewed the French trial for me. They agreed, separately, that while the study is preliminary, small, and not without flaws, its findings were strong enough, given the drugs’ known safety records, to guide treatment decisions in a crisis.
“Despite the limitations of this study, in the absence of any effective treatment, in this urgent situation, this Plaquenil and Azithromycin combination therapy should be given to patients with COVID-19 as a treatment option,” Ying Zhang, a professor of microbiology at Johns Hopkins Bloomberg School of Public Health, wrote in an email. “For now, there is no time to wait."
Brian Fallon, a research scientist and clinical trials investigator at the Columbia University Irving Medical Center, agreed on the study’s overall merit despite the patients who dropped out. After analyzing the data and counting all six dropouts as treatment failures, he said the overall rate of improvement was still statistically significant for the entire group, though not for the hydroxychloroquine group alone."
https://www.forbes.com/sites/marybethpfeiffer/2020/03/22/one...
[+] [-] stevespang|6 years ago|reply
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[+] [-] eruditegamer420|6 years ago|reply
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[+] [-] Proven|6 years ago|reply
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