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3 Last revised: February 2, 2021 Lay Summary BACKGROUND • Ivermectin is used to treat parasitic infections (such as intestinal worms or lice) in both humans and animals. Ivermectin is generally safe when used according to the label, but can cause mild side effects like nausea, diarrhea, fatigue, dizziness, and rash. • Laboratory studies performed in monkey cells showed that ivermectin is able to stop the virus that causes COVID-19 from growing in cells. This raised interest in ivermectin as a potential treatment for COVID-19, even though many medicines that are effective in the laboratory are not effective when they are used in people. • There is a lot of hype about ivermectin in social media, but it is still unclear if ivermectin actually prevents COVID-19 infection or is an effective treatment for COVID-19 because of the way studies have been done so far. This review summarizes the scientific research of ivermectin to provide guidance to public health officials and clinicians. KEY FINDINGS • The studies evaluating ivermectin treatment are not high enough quality to properly decide if ivermectin is useful or not. Most studies did not clearly describe the effect of the other medications given to patients or what other factors might influence their findings (“confounding”), did not have an adequate comparator group to assess if there was a difference in patients given ivermectin, or were too small to be sure that any effect of ivermectin seen was real. • With respect to ivermectin's ability to prevent infection with COVID-19, four low quality studies showed that ivermectin may reduce the risk of COVID-19 infection; however, there were several confounding factors and we don’t know what else the study participants were doing that might have influenced their risk of infection. More studies are needed to show if ivermectin can be used to prevent infection. • With respect to ivermectin's ability to treat people with COVID-19, seven studies that had a control group (ie. a group of participants that did not receive ivermectin) reported the effect of ivermectin on death from COVID-19. Four showed that deaths from COVID-19 went down, while three showed that deaths from COVID-19 were not affected. All seven studies were small and were of low or very low quality, so we can’t be sure that their findings were real. More studies are needed to show if ivermectin can be used to treat COVID-19. • The available data on ivermectin purchasing in Alberta doesn’t clearly show us if it is being used for purposes other than parasitic infections (ie. for COVID-19). RECOMMENDATIONS • At this time, ivermectin should not be prescribed or taken to prevent COVID-19 outside of a clinical trial, as we need to establish whether it is truly useful. • At this time, ivermectin should not be prescribed or taken to treat COVID-19 outside of a clinical trial, as we need to establish whether it is truly useful. • Scientists in Alberta should support clinical trials of ivermectin to help clarify whether ivermectin is effective against COVID-19 or not. 4 Last revised: February 2, 2021 Authorship and Committee Members Name Contribution Rachael Erdmann Writing (Primary and grey literature evidence extraction; Downs & Black assessment of primary evidence; draft preparation and revisions) Sarah Andrews Writing (collation and summarization of ongoing clinical trials; AMSTAR-2 critical appraisal of meta-analyses) Lauren Seal Librarian (Database searching and preliminary results screening) Mark Yarema Primary scientific reviewer Lynora Saxinger, John Conly, Alastair Cribb Secondary scientific reviewers Braden Manns & Lynora Saxinger Scientific Advisory Group chairs (oversight and leadership responsibility) John Conly, Alexander Doroshenko, Shelley Duggan, Nelson Lee, Marcia Johnson, Elizabeth MacKay, Andrew McRae, Melissa Potestio, Jeremy Slobodan, Brandie Walker, Nathan Zelyas Discussion, revision, and approval of document © 2020, Alberta Health Services, COVID-19 Scientific Advisory Group This copyright work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivative 4.0 International license. You are free to copy and distribute the work including in other media and formats for non-commercial purposes, as long as you attribute the work to Alberta Health Services, do not adapt the work, and abide by the other licence terms. To view a copy of this licence, see https://creativecommons.org/licenses/by-nc-nd/4.0/. The licence does not apply to AHS trademarks, logos or content for which Alberta Health Services is not the copyright owner. Disclaimer: This material is intended for general information only and is provided on an "as is", "where is" basis. Although reasonable efforts were made to confirm the accuracy of the information, Alberta Health Services does not make any representation or warranty, express, implied or statutory, as to the accuracy, reliability, completeness, applicability or fitness for a particular purpose of such information. This material is not a substitute for the advice of a qualified health professional. Alberta Health Services expressly disclaims all liability for the use of these materials, and for any claims, actions, demands or suits arising from such use. 5 Last revised: February 2, 2021 Topic: Ivermectin as prophylaxis and treatment for COVID-19 1. What is the evidence for ivermectin as prophylaxis for COVID-19? 2. What is the evidence for 

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