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Ivermectin



You may have noticed I haven't blogged about the drug Ivermectin yet though it has been mentioned many, many times as a possible treatment since almost the start of the pandemic. The reason I haven't is because there has been no conclusive evidence-based research of its benefits in acute Covid-19 infections, and especially not in

Long Covid.


What is Ivermectin?

Ivermectin is an antiparasitic agent that has been used to treat scabies, river blindness, and filariasis. Vets give it to animals to prevent heartworm. It was discovered in 1975 and has been used worldwide for nearly five decades and appears on the WHO list of essential medicines.

Ivermectin binds to certain chloride channels on nerve and muscle cells, paralyzing the creature exposed to it. These channels are present in worm and insect nervous systems, which is why the drug works.

Humans have the channels too, but only in our brains and spinal columns. Since ivermectin can't cross the blood-brain barrier, we are spared from its effects.

But SARS-CoV-2 has no muscles or nerves so why the interest in ivermectin for this virus?

A lot of the support comes from the study "The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro" by a group that has done work showing that the drug may have antiviral properties by affecting a protein called importin that a lot of viruses hijack for their own uses.

Researchers infected a cell culture with SARS-CoV-2 and added various concentrations of ivermectin. They then measured viral replication and found that the drug — in a petri dish, at least — could dramatically inhibit the ability of the virus to reproduce.

BUT the inhibitory concentration of the drug, around 2.5 micromolar, is not achievable in real live humans. In fact, standard ivermectin dosing achieves blood concentrations of about 25 nanomolar, 100-fold less than what was needed in vitro. Lung concentrations are a bit higher than blood concentrations but still 50-fold less than what is needed to inhibit the virus in cells in culture.


So, if ivermectin is going to work in humans with COVID-19, it has to be via some other mechanism — anti-inflammation or something like this.


The WHO statement only a few months ago in March 2021 said that "the current evidence on the use of ivermectin to treat COVID-19 patients is inconclusive. Until more data is available, WHO recommends that the drug only be used within clinical trials".


The PRINCIPLE (Platform Randomised Trial of Treatments in the Community for Epidemic and Pandemic Illnesses) trial is the world’s largest clinical trial of possible COVID-19 treatments for recovery at home and in other non-hospital settings. Led by the University of Oxford, the initiative has so far recruited more than 5,000 volunteers from across the UK.

As part of this research the anti-parasitic drug ivermectin is being investigated in the UK as a possible treatment for COVID-19 in adults.


Professor Chris Butler, Joint Chief Investigator of the PRINCIPLE trial, said:

“Ivermectin is readily available globally, has been in wide use for many other infectious conditions so it’s a well-known medicine with a good safety profile, and because of the early promising results in some studies it is already being widely used to treat COVID-19 in several countries. By including ivermectin in a large-scale trial like PRINCIPLE, we hope to generate robust evidence to determine how effective the treatment is against COVID-19, and whether there are benefits or harms associated with its use.”

Participants enrolled in the study will be randomly assigned to receive a three-day course of oral ivermectin. They will be followed-up for 28 days and will be compared with participants who have been assigned to receive the usual standard of NHS care only.


Ivermectin is the seventh treatment to be investigated in the PRINCIPLE trial, and is currently being evaluated alongside the influenza antiviral, favipiravir.


On the 6th July 2021 Hill et al published "Meta-analysis of randomized trials of ivermectin to treat SARS-CoV-2 infection" in Open Forum Infectious Diseases which supports the ivermectin camp.


The UK based researchers conducted a meta-analysis of 24 random controlled trials which included 3328 patients with SARS-CoV-2 infection.


Key results:

A meta-analysis showed a 56% reduction in mortality along with improved viral clearance and clinical recovery in patients receiving ivermectin vs standard of care (control) treatment for SARS-CoV-2 infection

Ivermectin versus control (standard care) showed:

  • reduced mortality risk

  • improved viral clearance at day 7

  • improved clinical recovery

  • Among patients with mild/moderate infection, ivermectin reduced the risk of mortality by 70% versus control.


Ivermectin vesus control reduced:

  • time to viral clearance (mean difference −3 days)

  • time to clinical recovery (mean difference -2 days)

  • length of hospitalisation (mean difference −4 days)


These findings are important as they provide combined results of published and unpublished randomised controlled trials (RCTs) to inform current guidelines on the use of ivermectin for SARS-CoV-2 infection.


However there are things to note:

  • It included studies differed in dosage and treatment duration.

  • Many included trials were not peer-reviewed - and we are finding more and more that some have been fabricated

  • The standard of care used as the control arm varied between studies.


References

More information on Ivermectin can be found on Dr Been's YouTube channel -https://www.youtube.com/channel/UCrtd2wePvAl6RN_D-9jWVQQ

https://www.who.int/news-room/feature-stories/detail/who-advises-that-ivermectin-only-be-used-to-treat-covid-19-within-clinical-trials

https://academic.oup.com/ofid/advance-article/doi/10.1093/ofid/ofab358/6316214

https://www.univadis.co.uk/viewarticle/ivermectin-beneficial-in-improving-covid-19-outcomes-suggests-meta-analysis-748191?s1=news

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