While I agree that there is insufficient attention paid to ivermectin as a possible treatment in Western nations, I have seen far too much shoddy and conflicting data in the studies that are brought forward proposing it as prophylaxis and think the hype is a spiral that has amplified nonsense into prominence. People LOVE the idea of a panacea. While there is quite possibly something interesting going on there it has been hyped to the moon and back in a way it should not be.
The animal data I have seen that I trust the most (since it avoids many of the pitfalls of observational trials, and few people are doing randomized trials that are actually good and not shoddy as hell after chloroquine sucked all the oxygen out of the room) suggests there could be something there, but not in a way that would block epidemics. Animals that are infected and then dosed have no difference in viral levels but recover their sense of smell significantly faster and when you take tissue samples the levels of inflammatory and tissue-destroying signaling molecules are lower while the ones that are more classically associated with antiviral responses are higher. Leans me towards the idea that it could decrease severity and odds of falling into downwards spirals. I have been following the in vitro work on this from the beginning and my conclusion is that you’re probably looking at immunomodulatory effects that can help you not fall into the pathological attractors, and deal with long infections better, rather than doing anything about viral binding or replication, if any of it pans out.
This being said, given the safety profile of the drug I say the risk to reward ratio is pretty good if you pay close attention to contraindications and I see no reason for it to not be used and studied more.
With regards to repurposing drug studies being almost impossible, I am much much more angry that there are no good studies, and no studies at all outside India, for indomethacin. A much more promising and well defined antiviral mechanism there against cytoplasmic RNA viruses via host factors that works STUNNINGLY well on canine intestinal coronaviruses in vivo, and sars and sars-2 in culture, and when you dig carefully through the literature being already on it by prescription is associated with much lower covid hospitalization risk.
My reading on ivermectin is that the concentrations required to be effective outside of in vitro would be extremely high. For what it’s worth, here are a few articles. Science is an evolving understanding of complex systems. Time and testing will tell.
“Laboratory studies using monkey cells in a test tube (as opposed to clinical studies in human patients) have shown ivermectin can shut down the replication of SARS-CoV-2, the coronavirus that causes COVID-19, within 24-48 hours of exposure to the drug.
Ivermectin is thought to inhibit the virus by preventing viral proteins moving in and out of the host cell’s nucleus, which is essential for replication of the coronavirus.
The problem is this process requires very high concentrations of ivermectin – well above the recommended dose for humans. This means ivermectin’s virus-killing powers would be unlikely to be harnessed inside the human body.”
(there are several linked references from within the article as well)
This next link is excellent—it delves into the molecular science w/out becoming incomprehensibly dense and there are three updates appended to the end showing promise.
The mechanisms stopping growth in vitro at obscene concentrations I agree are probably not operative in vivo, or at the very best not in the same way. However there are other bits of data regarding the drug as an immunomodulator in other viral infections, and this virus in particular has much of its pathogenesis having to do with badly regulated immune reactions.
Basically I am at the awkward position where I think the risk to potential reward ratio is favorable and that good research is needed while thinking most of the existing research is super shoddy.
One other thing to consider is that even small differences in replication rate might actually matter. Consider that it takes a week for the virus to really ramp up, and that’s a large number of doubling periods. Even just getting a larger or smaller initial dose seems linked to how sick people get. Even a few percent difference may allow the immune system to stay ahead in the arms race, and result in a nonlinear change in death rate.
Note that I’m not saying this happens; I’m saying that because this is an exponential growth attacker (the virus) versus and exponential growth responder (the immune system), even small differences in growth rates might have a large impact.
While I agree that there is insufficient attention paid to ivermectin as a possible treatment in Western nations, I have seen far too much shoddy and conflicting data in the studies that are brought forward proposing it as prophylaxis and think the hype is a spiral that has amplified nonsense into prominence. People LOVE the idea of a panacea. While there is quite possibly something interesting going on there it has been hyped to the moon and back in a way it should not be.
The animal data I have seen that I trust the most (since it avoids many of the pitfalls of observational trials, and few people are doing randomized trials that are actually good and not shoddy as hell after chloroquine sucked all the oxygen out of the room) suggests there could be something there, but not in a way that would block epidemics. Animals that are infected and then dosed have no difference in viral levels but recover their sense of smell significantly faster and when you take tissue samples the levels of inflammatory and tissue-destroying signaling molecules are lower while the ones that are more classically associated with antiviral responses are higher. Leans me towards the idea that it could decrease severity and odds of falling into downwards spirals. I have been following the in vitro work on this from the beginning and my conclusion is that you’re probably looking at immunomodulatory effects that can help you not fall into the pathological attractors, and deal with long infections better, rather than doing anything about viral binding or replication, if any of it pans out.
See, as an example, https://www.biorxiv.org/content/10.1101/2020.11.21.392639v1.full
This being said, given the safety profile of the drug I say the risk to reward ratio is pretty good if you pay close attention to contraindications and I see no reason for it to not be used and studied more.
With regards to repurposing drug studies being almost impossible, I am much much more angry that there are no good studies, and no studies at all outside India, for indomethacin. A much more promising and well defined antiviral mechanism there against cytoplasmic RNA viruses via host factors that works STUNNINGLY well on canine intestinal coronaviruses in vivo, and sars and sars-2 in culture, and when you dig carefully through the literature being already on it by prescription is associated with much lower covid hospitalization risk.
My reading on ivermectin is that the concentrations required to be effective outside of in vitro would be extremely high. For what it’s worth, here are a few articles. Science is an evolving understanding of complex systems. Time and testing will tell.
“Laboratory studies using monkey cells in a test tube (as opposed to clinical studies in human patients) have shown ivermectin can shut down the replication of SARS-CoV-2, the coronavirus that causes COVID-19, within 24-48 hours of exposure to the drug.
Ivermectin is thought to inhibit the virus by preventing viral proteins moving in and out of the host cell’s nucleus, which is essential for replication of the coronavirus.
The problem is this process requires very high concentrations of ivermectin – well above the recommended dose for humans. This means ivermectin’s virus-killing powers would be unlikely to be harnessed inside the human body.”
(there are several linked references from within the article as well)
https://theconversation.com/amp/ivermectin-is-still-not-a-miracle-cure-for-covid-19-despite-what-you-may-have-read-144569
This next link is excellent—it delves into the molecular science w/out becoming incomprehensibly dense and there are three updates appended to the end showing promise.
https://blogs.sciencemag.org/pipeline/archives/2020/05/11/whats-up-with-ivermectin
Another very useful article:
https://www.isglobal.org/en/healthisglobal/-/custom-blog-portlet/questions-and-answers-about-ivermectin-and-covid-19/2877257/0
mng
The mechanisms stopping growth in vitro at obscene concentrations I agree are probably not operative in vivo, or at the very best not in the same way. However there are other bits of data regarding the drug as an immunomodulator in other viral infections, and this virus in particular has much of its pathogenesis having to do with badly regulated immune reactions.
Basically I am at the awkward position where I think the risk to potential reward ratio is favorable and that good research is needed while thinking most of the existing research is super shoddy.
One other thing to consider is that even small differences in replication rate might actually matter. Consider that it takes a week for the virus to really ramp up, and that’s a large number of doubling periods. Even just getting a larger or smaller initial dose seems linked to how sick people get. Even a few percent difference may allow the immune system to stay ahead in the arms race, and result in a nonlinear change in death rate.
Note that I’m not saying this happens; I’m saying that because this is an exponential growth attacker (the virus) versus and exponential growth responder (the immune system), even small differences in growth rates might have a large impact.