ABSTRACT
SARS-CoV-2 epidemics raises a considerable issue of public health at the planetary scale. There is a pressing urgency to find treatments based upon currently available scientific knowledge. Therefore, we tentatively propose a hypothesis which hopefully might ultimately help saving lives. Based on the current scientific literature and on new epidemiological data which reveal that current smoking status appears to be a protective factor against the infection by SARS-CoV-2 [1], we hypothesize that the nicotinic acetylcholine receptor (nAChR) plays a key role in the pathophysiology of Covid-19 infection and might represent a target for the prevention and control of Covid-19 infection.
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, prevent clinical deterioration, reduce olfactory deficit, and limit 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.
Subject(s)
COVID-19 , Ivermectin , Animals , Humans , Lung , Pandemics , SARS-CoV-2ABSTRACT
SARS-CoV-2 epidemics raises a considerable issue of public health at the planetary scale. There is a pressing urgency to find treatments based upon currently available scientific knowledge. Therefore, we tentatively propose a hypothesis which hopefully might ultimately help save lives. Based on the current scientific literature and on new epidemiological data which reveal that current smoking status appears to be a protective factor against the infection by SARS-CoV-2 [1], we hypothesize that the nicotinic acetylcholine receptor (nAChR) plays a key role in the pathophysiology of Covid-19 infection and might represent a target for the prevention and control of Covid-19 infection.
L'épidémie de SARS-Cov-2 pose un problème considérable de santé publique à l'échelle planétaire. Il y a urgence extrême de découvrir des traitements qui se fondent sur les connaissances scientifiques disponibles. Nous proposons donc une hypothèse plausible mais provisoire qui puisse le moment venu contribuer à sauver des vies. Elle se fonde sur la littérature scientifique disponible et sur des données épidémiologiques nouvelles qui révèlent que le statut de fumeur parait être un facteur de protection contre l'infection par SARS-Cov-2 [1]. Nous proposons l'hypothèse que le récepteur nicotinique de l'acétylcholine (nAChR) joue un rôle critique dans la pathophysiologie de l'infection Covid-19 et puisse représenter une cible pour la prévention et le contrôle de l'infection.