Introduction
Ivermectin was initially developed as an anthelmintic medication for systemic conditions like Onchocerciasis, Strongyloidiasis, and Lymphatic Filariasis. But the sudden emergence of the Sars-Covid virus with its transition into a pandemic pushed researchers into modifying it as a possible treatment option for Covid. In Vitro, studies showed that a single dose of it resulted in a ~5000-fold reduction in viral replication within 48 hours while inhibiting viral binding to ACE-2 receptors.
But misuse of the medication has led to many complications regarding its stock, supply, and availability to people who actually need it. Veterinary use of Ivermectin has also increased because of a lack of awareness regarding the toxicities associated with using it designed for animals like horses, dogs, and sheep. The number of it prescriptions has increased 24 times than before the pandemic, indicating gross overuse of the medication followed by adverse reactions associated with it. Most importantly, there are a lot of controversies regarding the studies related to Ivermectin use for Covid that are an important source of determining its effectiveness.
Is Ivermectin harmful or helpful in the treatment of Covid-19
As per the meta-analysis of 15 trials including 2438 subjects, Moderate-certainty evidence finds that significant reductions in COVID-19 deaths are possible using it. The study concluded that using Ivermectin in the early stages of the infection can prevent it from progressing. It even emphasized that the drug’s safety and low cost could have a global impact on the pandemic.
Image Source:- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8248252/
Even reports from Peru-based studies showed a positive graph in favor of Ivermectin for Covid. Peru had a high death toll from Covid complications in the early stages of the pandemic. Based on observational evidence, the Peruvian government approved Ivermectin for use for Covid, after the implementation of which death rates reduced between 64% and 91% over two months. Another Peruvian analysis conducted over twenty-four states recorded a drop in excess deaths of 59% at thirty days and 75% at forty-five days.
But other meta-analyses showed other results for the use of Ivermectin for Covid.
In a study conducted to assess the efficacy and safety of Ivermectin for COVID-19, researchers studied completed and ongoing investigations by referencing Cochrane COVID-19 Study Register, Web of Science (Emerging Citation Index and Science Citation Index), medRxiv, and Research Square, and other valid websites.
The study aimed to assess the efficacy and safety of Ivermectin compared to no treatment, standard of care, placebo, or other proven intervention for people with COVID-19. Included subjects were receiving treatment as inpatients or outpatients and for prevention of infection with SARS-CoV-2 through postexposure prophylaxis.
The study included randomized controlled trials of people confirmed with Covid diagnosis receiving it as a part of their treatment. Those studies comparing Ivermectin to other pharmacological interventions or those with a high risk of bias were excluded.
A total of 14 studies with 1678 participants were chosen with varying intensities of infection among the subjects. There were nine outpatient studies, four inpatient studies, and one preventative study. Grading of the evidence was conducted to simplify the results. None of these studies compared Ivermectin to an intervention with proven accuracy.
Out of the 41 study results contributed by included studies, about a third were at an overall high risk of bias. The doses and treatment duration varied among the included studies, and some were awaiting classification until the publication of results or clarification of inconsistencies. Overall, researchers were uncertain whether the use of Ivermectin reduced or increased mortality, decreased the need for mechanical ventilation or supplemental oxygen, or led to viral clearance within seven days of use.
Even in comparison to the placebo, its use had little or no effect on the number of participants, with symptoms resolved up to 14 days. Nor did any study report hospital admission or quality of life up to 14 days. Based on the insufficient evidence, researchers concluded that they were uncertain about the efficacy and safety of Ivermectin in treating or preventing Covid-19.
What about veterinary Ivermectin
Veterinary Ivermectin, or Ivermectin for domestic animals, was the initial ivermectin product developed before the drug was modified for human use. Veterinary Ivermectin treats heartworms and parasitic infections in animals and is vastly different from human Ivermectin in terms of concentration and inactive ingredients.
Veterinary medications are usually of an increased concentration because of being used for large animals like horses and cows that weigh much more than average-sized human beings. Additionally, they contain many inactive ingredients that have not been declared safe for humans. Alternatively, the inactive ingredients are included in much larger quantities than safe for human consumption, especially with an altered immune response owing to Covid.
Using these drugs for human purposes can lead to overdosing symptoms of hepatic failure, breathing difficulties, and in some cases, even prove life-threatening. In the reports published by the Oregon poison Centre regarding toxic effects through the use of Ivermectin for Covid, 21 people had experienced Ivermectin toxicity.
Of these, 11 persons had used veterinary Ivermectin as a prophylactic, and 11 had used it to treat symptoms of active Covid. Three persons had received prescriptions from physicians or veterinarians, and the remaining had purchased veterinary formulations and used them. Symptoms developed in most people within two hours in the form of gastrointestinal distress, rashes, hypotension, vision disturbances, and fatigue.
In six people, the symptoms had developed gradually over several days to weeks. The dose strength ranged from 6.8mg to 125mg of 1.87% paste and 20-50mg of 1% solution of veterinary Ivermectin. All subjects need to be hospitalized, with some requiring intensive care for complications like seizures and ataxia impacting their hand-eye coordination and speech.
Fda verdict
The FDA has not approved or authorized ivermectin use for COVID-19, and other federal agencies have warned against using it for relief from symptoms of Covid. Eminent medical associations like American Medical Association, European Medical Association, and the WHO have reviewed the latest evidence on the use of it for the prevention and treatment of COVID-19 and concluded the dangers of using it injudiciously.
In a guideline development group of WHO convened to evaluate the role of Ivermectin for Covid, the conclusion after reviewing pooled data from 16 randomized controlled trials was the verdict that there was unsatisfactory evidence on the efficiency of Ivermectin for Covid.
Conclusion
While it is true that in the initial stages of the pandemic, it was regarded as a potential treatment option for Covid conditions, researchers found out later that the strength in which it was effective for the virus was much higher than safe limits. Additionally, the studies regarding its effectiveness were controversial in their methods and of an overall mixed quality.
It is highly effective against parasitic infections. But its use in Covid should be conducted only in clinical settings for patient safety. Animal Ivermectin is highly toxic to human beings and can prove life-threatening.
Most importantly, its use for Covid should be done only under the supervision of a physician when other treatment options are unavailable or not feasible because of allergic/tolerance problems.
References
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8248252/
https://pubmed.ncbi.nlm.nih.gov/34318930/
https://www.sciencedirect.com/science/article/pii/S0166354220302011
https://www.nejm.org/doi/full/10.1056/NEJMc2114907
