Anti-COVID-19 efficacy of ivermectin in the golden hamster
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Abstract
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.
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SciScore for 10.1101/2020.11.21.392639: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IACUC: Ethics: All animal experiments were performed according to the French legislation and in compliance with the European Communities Council Directives (2010/63/UE, French Law 2013–118, February 6, 2013) and according to the regulations of Pasteur Institute Animal Care Committees. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable SARS-CoV-2 model and ivermectin treatment of hamsters: Male and female Syrian hamsters (Mesocricetus auratus) of 5-6 weeks of age (average weight 60-80 grams) were purchased from Janvier Laboratories and handled under specific pathogen-free conditions. Cell Line Authentication not … SciScore for 10.1101/2020.11.21.392639: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IACUC: Ethics: All animal experiments were performed according to the French legislation and in compliance with the European Communities Council Directives (2010/63/UE, French Law 2013–118, February 6, 2013) and according to the regulations of Pasteur Institute Animal Care Committees. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable SARS-CoV-2 model and ivermectin treatment of hamsters: Male and female Syrian hamsters (Mesocricetus auratus) of 5-6 weeks of age (average weight 60-80 grams) were purchased from Janvier Laboratories and handled under specific pathogen-free conditions. Cell Line Authentication not detected. Table 2: Resources
Experimental Models: Cell Lines Sentences Resources The tubes were centrifuged at 10.000 x g during 1 min at 4°C, and the supernatants were titrated on Vero-E6 cells by classical plaque assays using semisolid overlays (Avicel, RC581-NFDR080I, DuPont)31. Statistics: Statistical analysis was performed using Prism software (GraphPad, version 9.0.0, San Diego, USA), with p < 0.05 considered significant. Vero-E6suggested: NoneSoftware and Algorithms Sentences Resources Generated data were subsequently analyzed with QuantaSoft™ software (Bio-Rad) based on positive and negative droplet populations. QuantaSoft™suggested: NoneThe tubes were centrifuged at 10.000 x g during 1 min at 4°C, and the supernatants were titrated on Vero-E6 cells by classical plaque assays using semisolid overlays (Avicel, RC581-NFDR080I, DuPont)31. Statistics: Statistical analysis was performed using Prism software (GraphPad, version 9.0.0, San Diego, USA), with p < 0.05 considered significant. Prismsuggested: (PRISM, RRID:SCR_005375)GraphPadsuggested: (GraphPad Prism, RRID:SCR_002798)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
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SciScore for 10.1101/2020.11.21.392639: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable Data were obtained from three independent experiments for males and two independent experiments for females. Table 2: Resources
No key resources detected.
Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.
Results from TrialIdentifier: No clinical trial numbers …
SciScore for 10.1101/2020.11.21.392639: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable Data were obtained from three independent experiments for males and two independent experiments for females. Table 2: Resources
No key resources detected.
Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.
Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
About SciScore
SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.
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