Abstract: Review of the Emerging Evidence Demonstrating the Efficacy of Ivermectin in the Prophylaxis and Treatment of COVID-19 Pierre Kory, MD1*, G. Umberto Meduri, MD2†, Jose Iglesias, DO3, Joseph Varon, MD4, Keith Berkowitz, MD5, Howard Kornfeld, MD6, Eivind Vinjevoll, MD7, Scott Mitchell, MBChB8, Fred Wagshul, MD9, Paul E. Marik, MD10 1 2 3 4 5 6 7 8 9 10 Front-Line Covid-19 Critical Care Alliance Memphis VA Medical Center, Univ. of Tennessee Health Science Center, Memphis, TN Hackensack School of Medicine, Seton Hall, NJ. Chief of Critical Care at United Memorial Medical Center in Houston, TX Center for Balanced Health, New York Recovery Without Walls Volda Hospital, Volda, Norway Princess Elizabeth Hospital, Guernsey, UK Lung Center of America, Dayton, Ohio Eastern Virginia Medical School * Correspondence: Corresponding Author: Pierre Kory, MD, MPA pkory@flccc.net 1 These authors have contributed equally to this work † Dr. Meduri’s contribution is the result of work supported with the resources and use of facilities at the Memphis VA Medical Center. The contents of this commentary do not represent the views of the U.S. Department of Veterans Affairs or the United States Government Keywords Ivermectin, COVID-19, infectious disease, pulmonary infection, respiratory failure Abstract In March 2020, the Front Line COVID-19 Critical Care Alliance (FLCCC) was created and led by Professor Paul E. Marik to continuously review the rapidly emerging basic science, translational, and clinical data to develop a treatment protocol for COVID-19. The FLCCC then recently discovered that ivermectin, an anti-parasitic medicine, has highly potent anti-viral and anti-inflammatory properties against COVID-19. They then identified repeated, consistent, large magnitude improvements in clinical outcomes in multiple, large, randomized and observational controlled trials in both prophylaxis and treatment of COVID-19. Further, data showing impacts on population wide health outcomes have www.flccc.net Review of the Emerging Evidence Supporting the Efficacy of Ivermectin in the Prophylaxis and Treatment of COVID-19 [FLCCC Alliance; updated Jan 16, 2021] 2 / 30 resulted from multiple, large “natural experiments” that occurred when various city mayors and regional health ministries within South American countries initiated “ivermectin distribution” campaigns to their citizen populations in the hopes the drug would prove effective. The tight, reproducible, temporally associated decreases in case counts and case fatality rates in each of those regions compared to nearby regions without such campaigns, suggest that ivermectin may prove to be a global solution to the pandemic. This was further evidenced by the recent incorporation of ivermectin as a prophylaxis and treatment agent for COVID-19 in the national treatment guidelines of Belize, Macedonia, and the state of Uttar Pradesh in Northern India, populated by 210 million people. To our knowledge, the current review is the earliest to compile sufficient clinical data to demonstrate the strong signal of therapeutic efficacy as it is based on numerous clinical trials in multiple disease phases. One limitation is that half the controlled trials have been published in peer-reviewed publications, with the remainder taken from manuscripts uploaded to medicine pre-print servers. Although it is now standard practice for trials data from pre-print servers to immediately influence therapeutic practices during the pandemic,..