Favorable clinical outcome for ivermectin in the COVID-19 animal model

The coronavirus disease (COVID-19) pandemic, caused by severe acute respiratory syndrome (SARS-CoV-2), has caused more than 59 million cases globally.

There is currently no vaccine or drug approved for the infection. However, doctors and scientists are using repurposed drugs to help hospitalized patients recover faster and improve clinical outcomes.

One of the proposed drugs is the antiparasitic drug ivermectin (IVM).

A team of researchers from the Institut Pasteur in France found that ivermectin prevents clinical deterioration in infected animals. The drug also reduced the inflammatory cytokines, interleukin-6 and 10 (IL-6 and IL-10) in lung tissue, which leads to more favorable clinical outcomes in treated animals.

What is ivermectin?

Ivermectin is an FDA approved broad-spectrum antiparasitic agent. Initially introduced as a veterinary drug, it kills a wide range of internal and external parasites in commercial livestock. In recent years, ivermectin has been used to treat various diseases, with its antimicrobial and antiviral properties.

The use of the drug has recently been proposed due to its potential anti-SARS-CoV-2 activity.

“Ivermectin is a positive allosteric modulator of the nicotinic receptor alpha-7 of acetylcholine, which has been suggested to be a target for controlling Covid-19 infection, with potential immunomodulatory activity,” the researchers wrote in document.

I study

The studio, which appeared on the prepress service bioRxiv *, aimed to study the effects of ivermectin alone on SARS-CoV-2 infection using golden Syrian hamsters as models for COVID-19.

The researchers inoculated the animals with SARS-CoV-2, which caused a symptomatic infection. The hamsters showed a high incidence of anosmia or loss of smell and high viral loads in the upper and lower airways within four days.

The team also administered a single subcutaneous injection of ivermectin at the time of infection. They monitored the hamsters for four days. Meanwhile, the infected mock animals received only a saline solution.

Clinical presentation and olfactory test of SARS-CoV-2 infected hamsters with and without ivermectin treatment. a. clinical signs and olfactory deficit in all infected hamsters. b, clinical signs and olfactory deficit only in infected male hamsters. c, clinical signs and olfactory deficit only in infected female hamster. The clinical score is based on a cumulative 0-4 scale: ruffled fur; slow movements; apathy; stress when manipulated. The smell test is based on the buried food finding test. The curves represent the percentage of animals that did not find buried food. Food search tests were performed 3 days after infection. Mann-Whitney test at 4 dpi (clinical signs) and Log rank test (Mantel-Cox) (olfactory tests). The p-value is shown in bold when significant at a threshold of 0.05. Symbols indicate the median ± interquartile range. Data were obtained from three independent experiments for males and two independent experiments for females.

Reduced olfactory deficit

The results of the study showed that ivermectin-treated and infected animals exhibited a reduction in the severity of clinical signs. Interestingly, the animal that received ivermectin had a reduced olfactory deficit.

About 66.7% of the mock animals had hyposmia or anosmia, compared with only 22.2% of those who received ivermectin.

Interleukin-6 and 10 (IL-6 and IL-10) in lung tissue

When the team treated the animals with ivermectin, there were notable differences between sex groups in the nasal turbinates. Female hamsters exhibited downregulation of some mediators, such as IL-6 and IL-10, tumor necrosis factor (Tnf-α) and CXC-motif chemokine ligand 10 (CXCL10). Meanwhile, men exhibited an increase in two pro-inflammatory mediators, interferon-gamma (IFNγ) and chemokine ligand 5 (Ccl5).

Furthermore, there is less expression of Cxcl10, a key mediator involved in respiratory disease and olfactory dysfunction in COVID-19 patients, in the nasal turbinates of animals treated with ivermectin-treated females without marked changes in males.

“These results are in line with the best performance of IVM-treated females seen in food-seeking tests,” the researchers explained.

The team found marked overexpression of interleukin 10 (IL-10) in males and females treated with IVM, which may be linked to modulation of the inflammatory response of the lungs.

In addition, the Il-6 / Il-10 ratio in the lung in IVM-treated hamsters was lower than in those not given the drug.

“In particular, the low Il-6 / Il-10 17 ratio observed in the lung of IVM-treated hamsters may predict their better clinical presentation, as observed in humans, as lower IL-6 / IL-10 plasma ratios are detected. Hospitalized COVID-19 patients who do not require intensive care, “the researchers wrote in the study.

The researchers concluded that ivermectin could be considered a new therapeutic agent against COVID-19. The drug can help improve patient prognosis as it leads to modulation of the cytokine gene expressed in the airways.

*Important Notice

bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, are not to be considered conclusive, guide clinical practice / health-related behavior, or treated as established information.