Ivermectin and COVID-19
Introduction:
You can skip the first three paragraphs of background if you
wish. As soon as SARS Corona Virus-2 made its impression on
scientists around the world, investigators with a wide range of
expertise began to apply their talents to this international problem.
The speed with which so many groups have developed various versions
of a COVID-19 vaccine has been impressive and welcome. As of the end
of December 2020 Canada had already approved the Pfizer-BioNTech and
Moderna vaccines with others close behind. Based on the history of
vaccine development and projections from various experts, I expected
vaccine availability a full year later than it has occurred. Earlier
in the year, March 14, we were locked down and being educated on
concepts such as social distancing, wearing masks, hand hygiene,
avoiding unnecessary social interactions, viral testing and contact
tracing.
Beyond this the
other big question was what kind of pharmacotherapy might be useful
in the treatment or prevention of COVID-19. As a result of my
earlier interest in vitamin D, its potential application in
prevention and treatment of this disease got my attention and
resulted in the writing of my blog on vitamin D and COVID-19 starting
in May. There have been a number of drugs that have been considered
for the treatment of COVID-19. These have included remdesivir,
chloroquine, hydroxychloroquine, calcifediol, doxycycline,
atorvastatin, zinc and steroids such as methylprednisoline. The one
that has caught my attention recently has been ivermectin.
Ivermectin is
the product of a systematic screening program for novel
antimicrobials conducted by Professor Satoshi Omura of the Kitasato
Institute in Tokyo working with Merck in the USA. The parasitology
department at Merck revealed that a group of macrocyclic lactones,
collectively called avermectins, had anti-parasitic activity. This is
discussed well in the context of novel anti-parasitic drug
development by WC Campbell (Lessons from the History of
Ivermectin and Other Antiparasitic Agents, Annual Review of Animal
Biosciences Volume 4, 2016 pp 1-14). Ivermectin made its
commercial debut 1981 as an antiparasitic agent for veterinary
applications. Ivermectin was introduced for human use in the
treatment of Onchocerciasis in 1987 , and one might be tempted to say
“the rest is history” because it has been such a success in the
treatment of a number of human parasites. Omura and Campbell were awarded the 2015 Nobel Prize in Physiology or Medicine.
My Bias
I
think that we should be using ivermectin for COVID-19 prophylaxis.
Given its
apparent effectiveness in this capacity along with its relatively low
risk of toxicity, its potential benefits far outweigh its negative
effects. If we were to acquire enough to treat the entire Canadian
population, we could save a tremendous amount of illness and prevent
untold deaths. Moreover the costs of using ivermectin would be minuscule compared to the current expenses for COVID treatment not to mention the indirect
costs to other aspects on our health and society at large; the latter
would include both social and financial costs. Below I
have described just some of the evidence regarding ivermectin in
COVID-19, but it should provide you with a flavour of its
potential for seeing us through this pandemic. Moreover ivermectin has substantial benefits once COVID-19 has been contracted but my focus today is prophylaxis.
Ivermectin as an anti-viral drug in laboratory
experiments. There are two papers that made an impression in
this respect. In the first in vitro Australian study, they showed that ivermectin
inhibited replication of SARS-CoV-2 in monkey kidney fibroblasts
and had an IC50 of ~2 μM.
The second but earlier (2014) in vivo study was done by a former
postdoctoral fellow, Robert Kinobe (currently a faculty member at James Cook
University in Townsville, QLD, Australia) and his colleagues.
Working in a veterinary environment, they worked on a non-human
species, crayfish, and showed that ivermectin at a dose of 7 μg/kg
blocked paroviruses therein
(https://doi.org/10.1016/j.aquaculture.2013.11.022). Experiments
such as these indicated that invermectin had the potential to be effective
in COVID-19.
Ivermectin effectiveness against COVID-19 in humans in
observational reports and clinical trials.
Observations:
The incidence of COVID-19 is much lower in sub-Saharan Africa than
was anticipated, and ivermectin has been used for many years in this
region for prophylaxis against parasitic infections. Accordingly
ivermectin may have reduced COVID-19 infectivity. See data on
COVID-19 in Africa in Worldometer. Also Hellwig and Maia (www.ncbi.nlm.nih.gov/pmc/articles/PMC7698683/) analyzed the relationship between ivermectin usage and COVID-19 and concluded that countries with routine mass drug administration of
prophylactic chemotherapy including ivermectin have a significantly
lower incidence of COVID-19. In another observational study in
France, 69 nursing home residents and 52 staff were treated with
ivermectin during a scabies outbreak. Seven of the 69 residents
fell ill with COVID-19 (10.1%);only one resident required oxygen and
none died. In a matched control group of residents from surrounding
facilities, 22.6% of residents fell ill and 4.9% died.
Human trials:
The Front Line COVID-19 Critical Care Alliance (FLCCC) is an
international team of experts who have reviewed as much information
as possible in order to develop prophylactic and curative treatments
for COVID-19. They have provided an excellent summary as guide for
the prevention and treatment of COVID-19 based information garnered
up to December 2020. Please see
https://covid19criticalcare.com/wp-content/uploads/2020/11/FLCCC-Ivermectin-in-the-prophylaxis-and-treatment-of-COVID-19.pdf.
In their summary of the protective effect of
ivermectin, they showed that this drug reduced and
sometimes eliminated the chances of
contracting COVID-19.
Benha University (Egypt) study. In a comparison of ivermectin
with hydroxychloroquine in patients with mild/moderate COVID-19
infection, the ivermectin patients did significantly better with
respect to symptoms, and none died in comparison with the four who
died in the hydroxychloroquine group. In patients with severe
COVID-19 infection, there were 2 deaths in the ivermectin group
versus 20 deaths in the hydroxychloroquine group. They also examined
the ability of ivermectin to protect against COVID-19 infection in
health care workers and household contacts of patients with confirmed
COVID-19. In these subjects ivermectin treatment resulted in an
infection rate of 2% compared with 10% amongst those who did not
receive ivermectin.
Egyptian registered clinical trial
(https://clinicaltrials.gov/ct2/show/results/NCT04422561) of
ivermectin as COVID-19 prophylactic agent. The study groups were
close family contacts of confirmed COVID-19 patients. In those who
received ivermectin (203 subjects) only 15 (7.4%) developed symptoms
of infection compared with 59 (58.4%) of 101 control subjects who did not
receive ivermectin.
In Argentina, health personnel from the Dr. Alberto Eurnekian
Interzonal University Hospital were recruited to test the ability of
carrageenen plus ivermectin to protect against laboratory confirmed
SARSCoV-2 infection. Of the 131 subjects in the
carrageenen/ivermectin group none tested positive while in the 98
controls subjects, 11 became positive. See
https://clinicaltrials.gov/ct2/show/results/NCT04425850.
Other references.
www.researchsquare.com/article/rs-100956/v1 Ivermectin reduced the incidence of infection in
health care and household contacts to 2% compared with 10% in non-ivermectin group.
www.ejmed.org/index.php/ejmed/article/view/599 73.3% (44 out of 60) subjects in control group were positive
for COVID-19, ivermectin reduced this to 6.9% (4 out of 58)
doi.org/10.1101/2020.10.29.20222661 Two-dose ivermectin prophylaxis, 300 μg/kg, was associated 73% reduction of COVID-19 infection among
healthcare workers in the subsequent month.
