Since the start of the COVID-19 pandemic, various therapeutic approaches have been explored to tackle the disease. Scientists from the Institut Pasteur have shown that ivermectin, a drug used commercially as an antiparasitic treatment, offers protection from COVID-19 symptoms in an animal model. The scientists observed that taking ivermectin was associated with reduced inflammation in the respiratory tract and an alleviation of the related symptoms. The treatment is also associated with protection against loss of smell. However, the results do not show any impact on the viral replication of SARS-CoV-2. The findings of the study suggest that ivermectin could be considered as a potential therapeutic agent for COVID-19. These results were published in the journal EMBO Molecular Medicine on July 12, 2021.
The COVID-19 pandemic has resulted in over 3.5 million deaths and more than 179 million confirmed cases of infection worldwide since it first began in December 2019.1 The disease caused by SARS-CoV-2 generally results in respiratory and pulmonary symptoms that can lead to fatal respiratory distress in severe cases. Several therapeutic approaches based on antivirals (like remdesivir) or immune modulators2 (like dexamethasone and tocilizumab) have been studied to combat COVID-19, but with limited therapeutic effects.3 The search for preventive and therapeutic approaches to tackle COVID-19 therefore remains a priority.
Scientists from the Institut Pasteur have studied the impact of the drug ivermectin on the clinical symptoms of COVID-19 in an animal model in the laboratory. Ivermectin is a drug in commercial use as an antiparasitic treatment that is being studied for use in treating other diseases. The authors of the study demonstrated that taking standard doses of ivermectin reduces the symptoms and severity of SARS-CoV-2 infection in an animal model.
"We chose to study ivermectin because it is an allosteric modulator of the nicotinic acetylcholine receptor (nAChR). This choice was based on the theory that the nAChR receptor plays a critical role in the pathophysiology of SARS-CoV-2 infection and could therefore represent a target for preventing and controlling infection," explains Guilherme Dias de Melo, a scientist in the Lyssavirus Epidemiology and Neuropathology Unit and first author of the study.
The findings of the study reveal that ivermectin modulates the immune response in animal models infected with SARS-CoV-2, lessening inflammation in the respiratory tract. This immunomodulatory effect helps reduce the emergence of symptoms of the disease. The scientists also demonstrated that the drug reduces the risk of animals losing their sense of smell. But they observed that treatment with ivermectin has no impact on SARS-CoV-2 viral replication.
"Surprisingly, we observed that treatment with ivermectin did not reduce viral replication; the models that received treatment had similar quantities of viral load in the nasal cavity and the lungs as those that did not receive treatment. Our results reveal that ivermectin has an immunomodulatory effect rather than an antiviral effect," comments Guilherme Dias de Melo.
In an opinion issued on March 31, 2021, WHO advised against the use of ivermectin to treat COVID-19 outside clinical trials until more data becomes available. As Guilherme Dias de Melo explains, "Our study generated preclinical data which scientifically demonstrate that ivermectin has a protective effect during SARS-CoV-2 infection in an animal model. These data provide crucial evidence to support clinical trials in humans."
Ivermectin has the potential to become an encouraging therapeutic agent to tackle COVID-19; while it has no impact on the replication of SARS-CoV-2, it attenuates inflammation and related symptoms.
"Our results represent a significant breakthrough, demonstrating that ivermectin belongs to a new category of COVID-19 drugs in an animal model. This research opens up new avenues for the development of more effective COVID-19 treatments in humans," concludes Hervé Bourhy, Head of the Lyssavirus Epidemiology and Neuropathology Unit and last author of the study.
1 WHO data from June 2021
2 Antivirals are drugs that limit viral replication. Immune modulators are drugs that act on the immune system and reduce inflammation
3 Data from the National Institutes of Health
Attenuation of clinical and immunological outcomes during SARS-CoV-2 infection by ivermectin, EMBO Molecular Medicine, 25 juin 2021
Guilherme Dias de Melo1, Françoise Lazarini2, Florence Larrous1, Lena Feige1, Etienne Kornobis3,4, Sylvain Levallois5, Agnès Marchio6, Lauriane Kergoat1, David Hardy7, Thomas Cokelaer3,4, Pascal Pineau6, Marc Lecuit5,8, Pierre-Marie Lledo2, Jean-Pierre Changeux9 and Hervé Bourhy1
1 Lyssavirus Epidemiology and Neuropathology Unit, Institut Pasteur, Paris, France
2 Perception and Memory Unit, Institut Pasteur, CNRS, UMR 3571, Paris, France
3 Biomics Technological Platform, Center for Technological Resources and Research (C2RT), Institut Pasteur, Paris, France
4 Bioinformatics and Biostatistics Hub, Computational Biology Department, Institut Pasteur, Paris, France
5 Biology of Infection Unit, Institut Pasteur, Inserm U1117, Paris, France
6 Nuclear Organization and Oncogenesis Unit, Institut Pasteur, Paris, France
7 Experimental Neuropathology Unit, Institut Pasteur, Paris, France
8 Université de Paris, Necker-Enfants Malades University Hospital, Division of Infectious Diseases and Tropical Medicine, Institut Imagine, AP-HP Paris, France
9 Neuroscience Department, Institut Pasteur and Collège de France, Paris, France