Abstract: medRxiv preprint doi: https://doi.org/10.1101/2020.11.30.20236570; this version posted December 4, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license . 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 THE THERAPEUTIC POTENTIAL OF IVERMECTIN FOR COVID-19: A SYSTEMATIC REVIEW OF MECHANISMS AND EVIDENCE Stefanie Kalfas, MD1 Kumar Visvanathan, MBBS FRACP PhD2,3 Kim Chan, DSc PhD4 John Drago, MBBS FRACP PhD1,5* 1 Florey Institute of Neuroscience and Mental Health, University of Melbourne, VIC, Australia Department of infectious Diseases, St. Vincent’s Hospital, Melbourne, VIC, Australia 3 Department of Medicine, Dentistry and Health Sciences, University of Melbourne, VIC, Australia 4 Sydney Pharmacy School, Faculty of Medicine and Health, University of Sydney, NSW, Australia 5 Department of Neurology, St. Vincent’s Hospital, Melbourne, VIC , Australia 2 *corresponding author: john.drago@florey.edu.au Word count (excluding abstract): 3,676 NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice. medRxiv preprint doi: https://doi.org/10.1101/2020.11.30.20236570; this version posted December 4, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license . 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 ABSTRACT Introduction: Ivermectin is a commonly used antihelminthic agent with over 35 years of established safety data in humans. Recent data demonstrates antiviral activity in vitro against SARS-CoV-2, in addition to a range of viruses. In vitro and animal models also provide evidence of immunomodulatory action. These additional modes of action are supported by in silico modelling, which propose a number of viral and host targets that would mediate these effects. Objectives: The aim of this study is to systematically review the published and preprint clinical literature and study results that assessed the potential role of ivermectin as a COVID19 therapeutic and prophylactic agent. Methods: We conducted a comprehensive review of PubMed, medRxiv, ClinicalTrials.gov, Global Coronavirus COVID-19 Clinical Trial Tracker, World Health Organization International Clinical Trials Registry Platform, EU Clinical Trials Register, ANZ clinical trials registry, and references from relevant articles. Results: Search keywords- “COVID-19 (and synonyms) AND ivermectin”- generated 86 articles on PubMed, 48 on medRvix and 37 on clinicaltrials.gov at the time of writing. Twelve of these were listed as completed clinical trials and of these, 8 were included as investigators had released results. Positive mortality benefit, reduced time to clinical recovery, reduced incidence of disease progression and decreased duration of hospital admission were reported in patients across all stages of clinical severity. Limitations: Due to the time-critical nature of the COVID-19 pandemic our review included preprint data, which must be interpreted with caution while it awaits peer review. medRxiv..