Anti-COVID-19 efficacy of ivermectin in the golden hamster

The devastating coronavirus disease 2019 (COVID-19) pandemic, due to SARS-CoV-2, has caused more than 47 million confirmed cases and more than 1.2 million human deaths around the globe ¹ , and most of the severe cases of COVID-19 in humans are associated with neurological symptoms such as anosmia and ageusia, and uncontrolled inflammatory immune response ^2–5 . Among therapeutic options ^6–8 , the use of the anti-parasitic drug ivermectin (IVM), has been proposed, given its possible anti-SARS-CoV-2 activity ⁹ . Ivermectin is a positive allosteric modulator of the α-7 nicotinic acetylcholine receptor ¹⁰ , which has been suggested to represent a target for the control of Covid-19 infection ¹¹ , with a potential immunomodulatory activity ¹² . We assessed the effects of IVM in SARS-CoV-2-intranasally-inoculated golden Syrian hamsters. Even though ivermectin had no effect on viral load, SARS-Cov-2-associated pathology was greatly attenuated. IVM had a sex-dependent and compartmentalized immunomodulatory effect, preventing clinical deterioration and reducing olfactory deficit in infected animals. Importantly, ivermectin dramatically reduced the Il-6/Il-10 ratio in lung tissue, which likely accounts for the more favorable clinical presentation in treated animals. Our data support IVM as a promising anti-COVID-19 drug candidate.