Review of the Emerging Evidence Demonstrating the Efficacy of Ivermectin in the Prophylaxis and Treatment of COVID-19

Today, I found this preprint on the efficacy of Ivermectin in COVID-19 prophylaxis and treatment. In the context of COVID-19, Ivermectin looks more promising than any other drug I've read results on. The meta-review is partially based on unpublished data, though; it will take time until all the referenced trial results will be published.

10.31219/osf.io/wx3zn

Here is a draft with up-to-date charts:

Meta-analysis of 21 studies

What got my attention, though, is another referenced preprint on post-COVID-19 fatigue treatment with Ivermectin. They couldn't verify if it is CFS because CFS guidelines usually require at least 6 months of persisting symptoms, so the link is currently being investigated. With Ivermectin, they achieved 94% remission in 33 patients. Ivermectin has a good safety profile, so I hope we will see more on this front.

POST-ACUTE OR PROLONGED COVID-19: IVERMECTIN TREATMENT FOR PATIENTS WITH PERSISTENT SYMPTOMS OR POST-ACUTE

 

I've just seen a Dr pleading at a senate hearing for the NIH to review the data on Ivermectin. He is super confident and it got my ear.

 

Ivermectin and COVID 19 - YouTube

 

@Tera Green This was mentioned in the YouTube comments of your referenced video. I can't find the comment anymore; it must have been removed. But I think is now more relevant than when it was filmed, not only in the context of Ivermectin and COVID-19 but also for CFS. CFS is a condition no medical field really wants to take responsibility for. Each group of scientists seems to follow their own narrative of what CFS is supposed to be. Science is fact-based. But when implicit assumptions are included in study designs and arguing, real science can propagate a narrative and personal opinion.

For example, take the studies that argue as if CFS is a misdiagnosis once comorbidity is diagnosed. The comorbidity is the fact, but to get to this conclusion, you have to make the assumption that a co-diagnosis excludes CFS for some reason. Without stating this assumption clearly in the paper, it becomes opinionating.

I observe similar tendencies with COVID-19 research when certain scientific circles tried to push the narrative of Remdesivir as a candidate but HCQ as a kind of conspiracy theory. Studies were designed to support these claims by administering HCQ in a very critical stage of hospitalization. Something that seems kind of nonsensical because the risk profile of HCQ clearly advised against its use once cardiovascular comorbidity becomes a major factor, as is the case for critical COVID-19 patients. The referenced meta-review also includes reviews on HCQ and Remdesivir. Even including the opinionating study designs, HCQ has similar efficacy on the patient outcome as Remdesivir has. Nevertheless, neither of both reaches what the early data on Ivermectin promises.

Dr. Pierre Kory, the pleading doctor in this senate hearing, only asked the NIH to review the data. Why is that important? The NIH used to advise against Ivermectin due to a lack of peer-reviewed data. By not reviewing data, there is no reviewed data to publish. By not having any published data, they can argue like there is no reason to look into Ivermectin as a candidate. This is why someone like Fauci can make the statement during a press briefing that "there is no evidence for" Ivermectin. This phrase is often used by pop-scientists as a rhetorical technique. It usually also includes the implicit assumption that only "solid data" of large studies can be considered evidence. This way, "weak evidence" becomes "no evidence". But the opinionating factor is that, while one part is told, the other part isn't told. An accurate statement for Ivermecting would be: "There is weak evidence to consider Ivermectin as a candidate for COVID-19 treatment. There is no evidence advising against its use unless other drugs are coadministered."

 

I don't understand that. NIH review is not peer review. Peer review occurs at journals as soon as data have been submitted, nothing to do with NIH. If nothing has been considered worth publishing in a journal things must be pretty bad since nowadays some journals publish pretty much anything.

 

Sorry for the confusion. I'm not very clear-headed today. The NIH was asked to review the data. They do not directly delegate peer-review but they act as a leading figure in the system, which means that they can delegate funds, adjust guidelines, and make advising statements regarding the therapeutic options. If the NIH makes the statement that an option is an eligible candidate, major circles of the science community will follow up. If they advise against something without mentioning the potential as a candidate, it will remain disregarded from most parts. Peer-reviews are also affected by this (including independent review groups). This means the whole topic won't receive much attention in referencing papers and meta-meta reviews and discussions. Without incentives and motivation for larger studies, the current state will not change and the NIH can continue making the statement that they advise against Ivermectin because there is no solid data to support it (this is the last state of their arguing). Without mentioning it as a candidate, as they did for Remdesivir, the US won't look into it and most of the research will keep coming from other countries that don't have the same amount of funding and scale.

 

I don't think that is right. Peer review is not in any way dependent on what government bodies do. Government bodies come along late in the process. The first thing is for scientists to publish - which includes peer review by colleagues who are usually very ready to do so. Incentives for drug studies come from industry or from independent academics like myself.

From what I can see there is no clear reason to invest in Ivermectin from a scientific perspective and drugs of this sort are often quite toxic. All drugs are candidates in a sense but this does not look a particularly attractive one.

 

I can not really agree with a generalizing argument that puts a therapeutic agent into a "sort of this" group unless they show similar means of action. But this isn't the frequent argument I read online in the press. The frequent argument is that it is a parasitic drug and how can you even consider some "sort of parasitic drug". The safety margin is 250x (for 200mcg/kg) in a rat model (10.1016/j.yrtph.2006.10.009). None of the COVID-19 trials used higher dosages than this meta-review considered to be safe (i.e. 200-400mcg/kg) (10.1093/jac/dkz524). HCQ has shown increased lethality in certain studies because of its severe risks in certain cases. No study indicates similar severe adverse effects for Ivermectin yet. Why don't we see any such reports for Ivermectin? Certain countries have widely distributed Ivermectin among the population already. From an ethical standpoint, you may see this critically of course. But why don't we see any reports of adverse effects from these countries?

 

Drugs that kill one organism and not another often have toxicities. A very general rule but not a bad one. Moreover, a quick look at PubMed suggests that Ivermectin may be teratogenic and the best figure for relative risk for fetal malformation is 1.69. The worst part of that is that billions of doses have been handout and nobody knows. I suspect it is mostly used in countries where documentation toxicity is even poorer than in well developed countries.

It may be safe. My caveat about safety was an afterthought.

 

Another interview with two well-known doctors sharing their medical opinions on the Ivermectin data at the time.

https://www.youtube.com/watch?v=C7J8SPczl6w

Meanwhile, we are at 44 studies on Ivermectin, 28 of which consistently showing the effectiveness of it with COVID-19, 17 of which are already peer-reviewed, 10 of which are RCTs, including double-blind and/or placebo-controlled trials, 4 of the studies also reviewing the safety profile, 2 in parallel with other drugs as well. As these two doctors say, however, there is the need for a larger trial. Billions have been spent on vaccine research. Why can't we see such attempts for repurposed drugs?

 

A hopeful guideline update by the NIH recognizing the emerging Ivermectin data.

https://www.youtube.com/watch?v=9R7IBAnFLV4