1/ There have been several small RCTs over the last weeks suggesting a clinical benefit for #ivermectin for #COVID_19.
It’s time for a MEGA THREAD on ivermectin, aka the “wonder drug”!
Let's start the show !🔥🔥🔥
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Ivermectin belongs to the family of avermectins, which are natural fermentation products of soil bacteria. A Nobel Prize of Medicine was awarded for their discovery.
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Ivermectin is indicated for several parasitic infections: onchocerciasis, lymphatic filariasis, strongyloidiasis, scabies. It works on head lice too. #NTDs
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For example, Anopheles mosquitoes who bite humans or animals treated by ivermectin don’t survive long. Hence the idea to regularly distribute massively ivermectin to humans and livestock in malaria-endemic areas for vector control! bohemiaconsortium.org
5/ Ivermectin is active in vitro against several RNA viruses, including flaviviruses.
It was actually evaluated for dengue in a Phase III randomized clinical trial in Thailand. Virological efficacy was demonstrated, but no clinical efficacy was shown. rcpt.org/abstractdb/med…
6/ Ivermectin is active against SARS-CoV-2, but the in vitro study in Vero Cells earlier this year found an EC50 that projected an unhittable dose. The methodology of this study has been criticized though.
7/ In addition to a putative direct antiviral effect, ivermectin might work for COVID-19 because of other mechanisms of action (MoA): inhibition of importins, interaction with nAChR receptors, etc.
Remember that one of the first papers reporting positive results for ivermectin against COVID-19 was a flawed Big Data study by researchers affiliated to Surgisphere. So this paper doesn’t count.
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A retrospective study suggesting a benefit for ivermectin was conducted in Miami, USA in March-May 2020. Lower mortality was found in the group of hospitalized COVID-19 patients receiving ivermectin.
11/ Multiple small studies of ivermectin were then launched:
➡️some observational / others randomized,
➡️low dose / high dose,
➡️monotherapy / in combination
➡️prophylaxis / treatment
Heterogeneity++. Unclear if it will be possible to conduct a meta-analysis…
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Many observational studies have been published, most often with positive results.
Ivermectin has also been used extensively in several countries in Latin America.
But I will now focus on studies coming from randomized clinical trials.
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In sum, the vast majority of RCTs of ivermectin-containing regimens for COVID-19 had positive results.
Word of caution: most of these studies have been published as preprints (not yet peer-reviewed). These papers need to be reviewed carefully to identify possible biases.
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Important to mention the safety profile of ivermectin.
Ivermectin is contraindicated during pregnancy. However, recent data seem fairly reassuring... thelancet.com/journals/langl…
16/ In very rare cases, mainly among people in central Africa infected by Loa loa, ivermectin has caused encephalopathy after crossing blood-brain barrier (BBB).
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I forgot to mention an important point: ivermectin is a cheap 💊 available as generics in many countries.
There is also a donation program by @Merck for NTDs (@MectizanMDP). But I don’t think Merck has shown interest (yet) for the repurposing of ivermectin for COVID-19.
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One last word. In the aftermath of the HCQ debacle, policy-makers are nervous when alleged miracle drugs for COVID-19 are praised in social media.
Fair enough...But please don’t censor groups who are discussing potential benefits of ivermectin!
19/ All these results put together call for urgent implementation of large scale RCTs of ivermectin for COVID-19. At what dose? In combination with another drug? To be discussed.
Mouthwash solutions of PVP-I can be easily purchased OTC in many countries. Nasal sprays and eye drops are less easily accessible (i.e. not available OTC in France).
There have been other in vivo and in vitro studies over the last months. A tiny RCT from Singapore had previously found encouraging results.
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In this thread, I’ll speak about #tocilizumab and challenges to access it. Tocilizumab is an anti-IL-6-receptor monoclonal antibody. It is a promising investigational drug to treat the cytokine storm associated with severe #COVID19.
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The cytokine storm (aka cytokine release syndrome) occurs when a high number of white blood cells are activated and release inflammatory cytokines, such as IL-6, which in turn activate more white blood cells.
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Tocilizumab is not an antiviral agent. Like other host focused therapies for COVID19, tocilizumab can be used in association with an effective antiviral and their combined actions may be complementary.
In this thread, I’ll share what is known about access to #remdesivir, one of the leading therapeutic candidates against #COVID19. Originator company @GileadSciences ($GILD). As an introduction, I suggest you should read this very detailed article. biopharmadive.com/news/coronavir… 1/n
Remdesivir (aka GS-5734) inhibits RNA-dependent RNA polymerase. Broad-spectrum antiviral. Injectable (IV). Wasn’t found as clinically effective for #Ebola as monoclonal antibodies. Here is the formula. The synthesis of GS-5734 is described here. pubs.acs.org/doi/full/10.10… 2/n
How much of remdesivir is available now ? Unclear. In Feb 2019, when drug was still a promising candidate for #Ebola, Gilead planned to have 25kg + 4x40g of (unfinished) drug substance by 2020, equivalent to 148,000 treatment courses. Unknown if it materialized. 3/n