Attenuation of clinical and immunological outcomes during SARS‐CoV‐2 infection by ivermectin
Guilherme Dias Melo, Françoise Lazarini, Florence Larrous, Lena Feige, Etienne Kornobis, Sylvain Levallois, Agnès Marchio, Lauriane Kergoat, David Hardy, Thomas Cokelaer, Pascal Pineau, Marc Lecuit, Pierre‐marie Lledo, Jean‐pierre Changeux, Hervé Bourhy
EMBO Molecular Medicine, doi:10.15252/emmm.202114122
The devastating pandemic due to SARS-CoV-2 and the emergence of antigenic variants that jeopardize the efficacy of current vaccines create an urgent need for a comprehensive understanding of the pathophysiology of COVID-19, including the contribution of inflammation to disease. It also warrants for the search of immunomodulatory drugs that could improve disease outcome. Here, we show that standard doses of ivermectin (IVM), an antiparasitic drug with potential immunomodulatory activities through the cholinergic anti-inflammatory pathway, prevent clinical deterioration, reduce olfactory deficit, and limit the inflammation of the upper and lower respiratory tracts in SARS-CoV-2infected hamsters. Whereas it has no effect on viral load in the airways of infected animals, transcriptomic analyses of infected lungs reveal that IVM dampens type I interferon responses and modulates several other inflammatory pathways. In particular, IVM dramatically reduces the Il-6/Il-10 ratio in lung tissue and promotes macrophage M2 polarization, which might account for the more favorable clinical presentation of IVM-treated animals. Altogether, this study supports the use of immunomodulatory drugs such as IVM, to improve the clinical condition of SARS-CoV-2-infected patients.
Author contributions JPC and HB conceived the experimental hypothesis. GDM, FLaz, FLar, and HB designed the experiments. GDM, FLaz, FLar, LF, LK, SL, AM, and DH performed the experiments. GDM, FLaz, FLar, LF, EK, SL, AM, TC, PP, ML, and P-ML analyzed the data. GDM, J-PC, and HB wrote the manuscript, and all authors edited it.
Conflict of interest The authors declare that they have no conflict of interest.
For more information • COVID-19 section of the WHO website: https://covid19.who.int/
References Aamir K, Khan HU, Sethi G, Hossain MA, Arya A (2020) Wnt signaling mediates TLR pathway and promote unrestrained adipogenesis and
The paper explained
Problem The current pandemic of COVID-19 has caused more than 3.5 million deaths and more than 150 million laboratory-confirmed cases worldwide since December 2019 (as of May 2021). COVID-19, caused by SARS-CoV-2, commonly brings about upper airways and pulmonary symptoms and in severe cases can lead to respiratory distress and death. Different therapeutic approaches have been proposed to fight this disease but comprehensive therapeutic studies are still lacking.
Results We report that ivermectin, used at the standard anti-parasitic dose of 400 µg/kg, protects infected hamsters from developing clinical signs and from losing the sense of smell during SARS-CoV-2 infection. The treated animals exhibited a specific inflammatory response, presenting a reduced type I/III interferon stimulation and a modulation in several..
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