5 ms·

A lot has been invested in drugs. Most of them don't work. The best that was found was Dexamethasone, which reduces mortality in severe cases significantly. Ge

by hannob 6y ago

A lot has been invested in drugs. Most of them don't work. The best that was found was Dexamethasone, which reduces mortality in severe cases significantly. Generally medication for viral infections seems to be hard. There isn't much good medication for other respiratory viral diseases. It doesn't look like a major breakthrough in drug treatment will happen. A vaccine can make the difference between "you get the disease" and "you don't get the disease and can't spread it to others". No drug comes remotely close to that.

amluto 6y ago
A lot of very competent coordinated studies of drugs have been done. Oh wait, no it hasn’t. We had a mishmash of variously competent and incompetent studies of AZ/HCQ. We have anecdotal data on ivermectin. We have some preliminary studies of fluvoxamine (excellent results, needs follow up); the large scale expedited follow up is MIA. It’s been over six months from the original study — there is no fundamental reason it should take more than two months to test it on a few tens of thousands of people. Ditto for anti-androgens. Camistat ought to have at least some effect (famous last words); this has been known for something like a year with no meaningful followup. What’s needed here is IMO public health department coordination on studies, which isn’t quite the same thing as money.
- entee 6y ago
  To be clear, almost all of these studies showed very small effect sizes. The best therapeutics we have are remdesevir (small but real effect on severity, unclear effect on hospitalization and death), dexamethosone (moderate to large effect on death when hospitalized), and antibody drugs for which Lilly’s has already been remove because ineffective against variants though Regeneron’s cocktail seems quite good. Fluvoxamine is I’m sure under investigation, we’ll get a readout eventually but that’s a relatively new result. The best drugs we have are either: 1.) treat the virus with a novel entity (Regeneron, the other antibodies) 2.) treat the inflammation (dexamethosone, possibly eventually fluvoxamine) The repurposing and general antivirals (including remdesevir) have little effect and likely won’t make a difference. There are novel drugs being developed (Pfizer just started a protease inhibitor trial) but that’s the only place I’d expect to see real impact, with fluvoxamine as a treat the symptoms wildcard. People have been trying to find drugs or repurpose, and academic medical centers have been working on it. It’s that almost nothing works when subjected to the hard trials.
  - maxerickson 6y ago
    There's likely room to pick better monoclonal antibodies to use. There was an antibody identified that smashed variants, for instance. https://www.medrxiv.org/content/10.1101/2021.01.26.21250224v2 https://www.medrxiv.org/content/10.1101/2021.01.26.21250224v... Some contextualization at https://twitter.com/K_G_Andersen/status/1367592606641704961 https://twitter.com/K_G_Andersen/status/1367592606641704961
  - nerdponx 6y ago
    Is the Regeneron drug an example of the "monoclonal antibodies" that I keep hearing about?
    - entee 6y ago
      Yes. Monoclonal antibodies are single antibodies that are produced at scale. Regeneron has 2 mABs that they mix to create a cocktail. Your immune system generated a polyclonal antibody response, which is to say it creates a multitude of different antibodies against the virus. If most aren’t great, that’s fine as long as one is good enough. If a few work together to neutralize the virus, that’s also fine. If you can identify one of those antibodies as especially good, you can then clone it and make a bunch of it artificially, hence “monoclonal”.
- nradov 6y ago
  There is now a lot more than just anecdotal data on ivermectin. This site has an index of the latest studies. Some show positive results, others show no effect or were inconclusive. Research continues. https://c19ivermectin.com/ https://c19ivermectin.com/
- nerdponx 6y ago
  This is actually McCullough's main thesis as far as I can tell ("we didn't study drugs enough and jumped straight to vaccine"), so it's interesting to hear it corroborated.
nradov 6y ago
Dexamethasone is no longer considered the best. The latest research indicates better results with methylprednisolone, which has a similar mechanism of action. https://pubmed.ncbi.nlm.nih.gov/33632000/ https://pubmed.ncbi.nlm.nih.gov/33632000/

by hannob 6y ago

amluto 6y ago

A lot of very competent coordinated studies of drugs have been done. Oh wait, no it hasn’t. We had a mishmash of variously competent and incompetent studies of AZ/HCQ. We have anecdotal data on ivermectin. We have some preliminary studies of fluvoxamine (excellent results, needs follow up); the large scale expedited follow up is MIA. It’s been over six months from the original study — there is no fundamental reason it should take more than two months to test it on a few tens of thousands of people. Ditto for anti-androgens. Camistat ought to have at least some effect (famous last words); this has been known for something like a year with no meaningful followup. What’s needed here is IMO public health department coordination on studies, which isn’t quite the same thing as money.

entee 6y ago
To be clear, almost all of these studies showed very small effect sizes. The best therapeutics we have are remdesevir (small but real effect on severity, unclear effect on hospitalization and death), dexamethosone (moderate to large effect on death when hospitalized), and antibody drugs for which Lilly’s has already been remove because ineffective against variants though Regeneron’s cocktail seems quite good. Fluvoxamine is I’m sure under investigation, we’ll get a readout eventually but that’s a relatively new result. The best drugs we have are either: 1.) treat the virus with a novel entity (Regeneron, the other antibodies) 2.) treat the inflammation (dexamethosone, possibly eventually fluvoxamine) The repurposing and general antivirals (including remdesevir) have little effect and likely won’t make a difference. There are novel drugs being developed (Pfizer just started a protease inhibitor trial) but that’s the only place I’d expect to see real impact, with fluvoxamine as a treat the symptoms wildcard. People have been trying to find drugs or repurpose, and academic medical centers have been working on it. It’s that almost nothing works when subjected to the hard trials.
- maxerickson 6y ago
  There's likely room to pick better monoclonal antibodies to use. There was an antibody identified that smashed variants, for instance. https://www.medrxiv.org/content/10.1101/2021.01.26.21250224v2 https://www.medrxiv.org/content/10.1101/2021.01.26.21250224v... Some contextualization at https://twitter.com/K_G_Andersen/status/1367592606641704961 https://twitter.com/K_G_Andersen/status/1367592606641704961
- nerdponx 6y ago
  Is the Regeneron drug an example of the "monoclonal antibodies" that I keep hearing about?
  - entee 6y ago
    Yes. Monoclonal antibodies are single antibodies that are produced at scale. Regeneron has 2 mABs that they mix to create a cocktail. Your immune system generated a polyclonal antibody response, which is to say it creates a multitude of different antibodies against the virus. If most aren’t great, that’s fine as long as one is good enough. If a few work together to neutralize the virus, that’s also fine. If you can identify one of those antibodies as especially good, you can then clone it and make a bunch of it artificially, hence “monoclonal”.
nradov 6y ago
There is now a lot more than just anecdotal data on ivermectin. This site has an index of the latest studies. Some show positive results, others show no effect or were inconclusive. Research continues. https://c19ivermectin.com/ https://c19ivermectin.com/
nerdponx 6y ago
This is actually McCullough's main thesis as far as I can tell ("we didn't study drugs enough and jumped straight to vaccine"), so it's interesting to hear it corroborated.

nradov 6y ago

Dexamethasone is no longer considered the best. The latest research indicates better results with methylprednisolone, which has a similar mechanism of action. https://pubmed.ncbi.nlm.nih.gov/33632000/ https://pubmed.ncbi.nlm.nih.gov/33632000/