Attenuation of clinical and immunological outcomes during SARS‐CoV‐2 infection by ivermectin

Guilherme Dias de Melo (1) , Françoise Lazarini (2) , Florence Larrous (1) , Lena Feige (1) , Etienne Kornobis (3, 4) , Sylvain Levallois (5) , Agnès Marchio (6) , Lauriane Kergoat (1) , David Hardy (7) , Thomas Cokelaer (3, 4) , Pascal Pineau (6) , Marc Lecuit (5, 8) , Pierre-Marie Lledo (2) , Jean‐pierre Changeux (9, 10) , Hervé Bourhy (1)

1 Lyssavirus, épidémiologie et neuropathologie - Lyssavirus Epidemiology and Neuropathology
2 Perception et Mémoire / Perception and Memory
3 Biomics (plateforme technologique)
4 Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB
5 Biologie des Infections - Biology of Infection
6 Organisation Nucléaire et Oncogenèse / Nuclear Organization and Oncogenesis
7 Neuropathologie expérimentale / Experimental neuropathology
8 Service des Maladies infectieuses et tropicales [CHU Necker]
9 CdF (institution) - Collège de France
10 Département de Neuroscience - Department of Neuroscience

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.

Mots clés: Coronavirus; Inflammation; Ivermectin; SARS-CoV-2; Viral Infections

Domaines: Sciences du Vivant [q-bio]; Immunologie; Microbiologie et Parasitologie; Virologie

Guilherme Dias de Melo, Françoise Lazarini, Florence Larrous, Lena Feige, Etienne Kornobis, et al.. Attenuation of clinical and immunological outcomes during SARS‐CoV‐2 infection by ivermectin. EMBO Molecular Medicine, 2021, 13 (8), pp.e14122. ⟨10.15252/emmm.202114122⟩. ⟨pasteur-03279176⟩