tetano
Editor, Senior Moderator
EMBO Mol Med
. 2021 Jun 25;e14122.
doi: 10.15252/emmm.202114122. Online ahead of print.
Attenuation of clinical and immunological outcomes during SARS-CoV-2 infection by ivermectin
Guilherme Dias de Melo[SUP] 1 [/SUP], Françoise Lazarini[SUP] 2 [/SUP], Florence Larrous[SUP] 1 [/SUP], Lena Feige[SUP] 1 [/SUP], Etienne Kornobis[SUP] 3 4 [/SUP], Sylvain Levallois[SUP] 5 [/SUP], Agnès Marchio[SUP] 6 [/SUP], Lauriane Kergoat[SUP] 1 [/SUP], David Hardy[SUP] 7 [/SUP], Thomas Cokelaer[SUP] 3 4 [/SUP], Pascal Pineau[SUP] 6 [/SUP], Marc Lecuit[SUP] 5 8 [/SUP], Pierre-Marie Lledo[SUP] 2 [/SUP], Jean-Pierre Changeux[SUP] 9 [/SUP], Hervé Bourhy[SUP] 1 [/SUP]
Affiliations
Abstract
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 anti-parasitic drug with potential immunomodulatory activities through the cholinergic anti-inflammatory pathway, prevents clinical deterioration, reduces olfactory deficit and limits the inflammation of the upper and lower respiratory tracts in SARS-CoV-2-infected 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.
Keywords: Coronavirus; Inflammation; Ivermectin; SARS-CoV-2; Viral Infections.
. 2021 Jun 25;e14122.
doi: 10.15252/emmm.202114122. Online ahead of print.
Attenuation of clinical and immunological outcomes during SARS-CoV-2 infection by ivermectin
Guilherme Dias de Melo[SUP] 1 [/SUP], Françoise Lazarini[SUP] 2 [/SUP], Florence Larrous[SUP] 1 [/SUP], Lena Feige[SUP] 1 [/SUP], Etienne Kornobis[SUP] 3 4 [/SUP], Sylvain Levallois[SUP] 5 [/SUP], Agnès Marchio[SUP] 6 [/SUP], Lauriane Kergoat[SUP] 1 [/SUP], David Hardy[SUP] 7 [/SUP], Thomas Cokelaer[SUP] 3 4 [/SUP], Pascal Pineau[SUP] 6 [/SUP], Marc Lecuit[SUP] 5 8 [/SUP], Pierre-Marie Lledo[SUP] 2 [/SUP], Jean-Pierre Changeux[SUP] 9 [/SUP], Hervé Bourhy[SUP] 1 [/SUP]
Affiliations
- PMID: 34170074
- DOI: 10.15252/emmm.202114122
Abstract
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 anti-parasitic drug with potential immunomodulatory activities through the cholinergic anti-inflammatory pathway, prevents clinical deterioration, reduces olfactory deficit and limits the inflammation of the upper and lower respiratory tracts in SARS-CoV-2-infected 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.
Keywords: Coronavirus; Inflammation; Ivermectin; SARS-CoV-2; Viral Infections.