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.