Read on Twitter
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 !
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 !
2/
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.
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.
3/
Ivermectin is indicated for several parasitic infections: onchocerciasis, lymphatic filariasis, strongyloidiasis, scabies. It works on head lice too. #NTDs
But ivermectin may have a broader therapeutic benefit. Hence its nickname, the “wonder drug”. https://pubmed.ncbi.nlm.nih.gov/28196978/
Ivermectin is indicated for several parasitic infections: onchocerciasis, lymphatic filariasis, strongyloidiasis, scabies. It works on head lice too. #NTDs
But ivermectin may have a broader therapeutic benefit. Hence its nickname, the “wonder drug”. https://pubmed.ncbi.nlm.nih.gov/28196978/
4/
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! https://bohemiaconsortium.org/
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! https://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.
http://www.rcpt.org/abstractdb/media/abstract/CON2018/Best%20Resident27/BRA_77_Eakkawit.pdf
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.
http://www.rcpt.org/abstractdb/media/abstract/CON2018/Best%20Resident27/BRA_77_Eakkawit.pdf
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. https://twitter.com/__ice9/status/1328303108615790592
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. https://twitter.com/__ice9/status/1328303108615790592
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.
All you need to know on MoAs here... and much more! https://www.isglobal.org/en/healthisglobal/-/custom-blog-portlet/questions-and-answers-about-ivermectin-and-covid-19/2877257/0
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.
All you need to know on MoAs here... and much more! https://www.isglobal.org/en/healthisglobal/-/custom-blog-portlet/questions-and-answers-about-ivermectin-and-covid-19/2877257/0
8/
Of note, recent animal in vivo studies for COVID-19 have given positive results.
Latest example here, by researchers from @institutpasteur https://twitter.com/julienpotet/status/1330827131392307200
Of note, recent animal in vivo studies for COVID-19 have given positive results.
Latest example here, by researchers from @institutpasteur https://twitter.com/julienpotet/status/1330827131392307200
9/
Now let’s have look at clinical data.
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. https://twitter.com/martinenserink/status/1268639646113763331
Now let’s have look at clinical data.
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. https://twitter.com/martinenserink/status/1268639646113763331
10/
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. https://twitter.com/julienpotet/status/1270369217158791168
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. https://twitter.com/julienpotet/status/1270369217158791168
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…
Multiple small studies of ivermectin were then launched:
some observational / others randomized, low dose / high dose, monotherapy / in combination prophylaxis / treatmentHeterogeneity++. Unclear if it will be possible to conduct a meta-analysis…
12/
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.
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.
13/
Ivermectin for COVID_19
Positive RCTs:
: https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3714649
: https://www.researchsquare.com/article/rs-109670/v1
: https://www.medrxiv.org/content/10.1101/2020.10.26.20219345v1
: https://www.researchsquare.com/article/rs-100956/v1
: https://www.ijidonline.com/article/S1201-9712(20)32506-6/fulltext
: https://www.researchsquare.com/article/rs-116547/v1
Negative RCTs:
: https://www.researchgate.net/publication/344240147_Outcome_of_ivermectin_treated_mild_to_moderate_COVID-19_cases_a_single-centre_open-label_randomised_controlled_study
Ivermectin for COVID_19
Positive RCTs:
: https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3714649 : https://www.researchsquare.com/article/rs-109670/v1 : https://www.medrxiv.org/content/10.1101/2020.10.26.20219345v1 : https://www.researchsquare.com/article/rs-100956/v1 : https://www.ijidonline.com/article/S1201-9712(20)32506-6/fulltext : https://www.researchsquare.com/article/rs-116547/v1Negative RCTs:
: https://www.researchgate.net/publication/344240147_Outcome_of_ivermectin_treated_mild_to_moderate_COVID-19_cases_a_single-centre_open-label_randomised_controlled_study
14/
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.
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.
15/
Important to mention the safety profile of ivermectin.
Ivermectin is contraindicated during pregnancy. However, recent data seem fairly reassuring... https://www.thelancet.com/journals/langlo/article/PIIS2214-109X(19)30490-5/fulltext
Important to mention the safety profile of ivermectin.
Ivermectin is contraindicated during pregnancy. However, recent data seem fairly reassuring... https://www.thelancet.com/journals/langlo/article/PIIS2214-109X(19)30490-5/fulltext
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).
Integrity of BBB may be disrupted in severe COVID-19 patients. So let’s be careful https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5929173/
In very rare cases, mainly among people in central Africa infected by Loa loa, ivermectin has caused encephalopathy after crossing blood-brain barrier (BBB).
Integrity of BBB may be disrupted in severe COVID-19 patients. So let’s be careful https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5929173/
17/
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.
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.
18/
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! https://twitter.com/Covid19Critical/status/1335653346603098113
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! https://twitter.com/Covid19Critical/status/1335653346603098113
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.
In any case, it is high time to seriously consider #ivermectin for #COVID_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.
In any case, it is high time to seriously consider #ivermectin for #COVID_19.
20/ END
#TropMed aficionados, if you have noticed a mistake in this thread about ivermectin for COVID-19, please feel free to correct me !
@carlos_chaccour @dr_michaelmarks @oriolmitja @PeterHotez @mwelentuli @DNDi @LSTM_NTDs @_Isra_Cruz @RSTMH @COR_NTD @SpringGombe @BangertMat
#TropMed aficionados, if you have noticed a mistake in this thread about ivermectin for COVID-19, please feel free to correct me !
@carlos_chaccour @dr_michaelmarks @oriolmitja @PeterHotez @mwelentuli @DNDi @LSTM_NTDs @_Isra_Cruz @RSTMH @COR_NTD @SpringGombe @BangertMat
