Prophylactic Effect of Ivermectin on SARS-CoV-2 Induced Disease in a Syrian Hamster Model
Uematsu et al.,
Prophylactic Effect of Ivermectin on SARS-CoV-2 Induced Disease in a Syrian Hamster Model,
Research Square, doi:10.21203/rs.3.rs-2012940/v1 (Preprint)
Hamster study showing that prophylactic ivermectin inhibited COVID-19 weight loss, reduced lung viral titer by a factor of 10, inhibited pulmonary inflammatory cytokine expression, and reduced the severity of pathological changes with a single 1mg/kg dose. Authors also tested 250 and 500µg/kg for inhibition of weight loss, showing a dose-response relationship. While not statistically significant, 500µg/kg also showed a trend for benefit.
Uematsu et al., 15 Sep 2022, preprint, 5 authors.
Contact:
tuematsu@insti.kitasato-u.ac.jp.
Abstract: Prophylactic Effect of Ivermectin on SARS-CoV-2
Induced Disease in a Syrian Hamster Model
Takayuki Uematsu ( tuematsu@insti.kitasato-u.ac.jp )
Kitasato University Medical Center
Tomomi Takano
Department of Veterinary Medicine, Kitasato University
Hidehito Matsui
Ōmura Satoshi Memorial Institute, Kitasato University
Noritada Kobayashi
Kitasato University Medical Center
Hideaki Hanaki
Ōmura Satoshi Memorial Institute, Kitasato University
Article
Keywords:
Posted Date: September 15th, 2022
DOI: https://doi.org/10.21203/rs.3.rs-2012940/v1
License: This work is licensed under a Creative Commons Attribution 4.0 International License.
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Abstract
COVID-19, caused by SARS-CoV-2 infection, is currently among the most important public health
concerns worldwide. Although several effective vaccines have been developed, there is an urgent clinical
need for effective pharmaceutical treatments for treatment of COVID-19. Ivermectin, a chemical derivative
of avermectin produced by Streptomyces avermitilis, is a macrocyclic lactone with antiparasitic activity.
Recent studies have shown that ivermectin inhibits SARS-CoV-2 replication in vitro. In the present study,
we investigated the in vivo effects of ivermectin in a hamster model of SARS-CoV-2 infection. The results
of the present study demonstrate oral administration of ivermectin prior to SARS-CoV-2 infection in
hamsters was associated with decreased weight loss and pulmonary inflammation. In addition, the
administration of ivermectin reduced pulmonary viral titers and mRNA expression level of proinflammatory cytokines associated with severe COVID-19 disease. The administration of ivermectin
rapidly induced the production of virus-specific neutralizing antibodies in the late stage of viral infection.
Zinc concentrations leading to immune quiescence were also significantly higher in the lungs of
ivermectin-treated hamsters compared to controls. These results indicate that ivermectin may have
efficacy in reducing the development and severity of COVID-19 by affecting host immunity in a hamster
model of SARS-CoV-2 infection.
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