Although there is now a small and increasing number of therapeutics showing some efficacy in important clinical outcomes, chief of which are corticosteroids in moderate to severe illness, the world continues to suffer from a worsening crisis with the potential of again overwhelming hospitals and intensive care units (ICU). In early 2020, on the onset of the spreading pandemic, many providers and institutions began to continuously review the rapidly emerging basic science, translational, and clinical data to identify potentially effective treatment options for COVID-19. Finally, the many examples of ivermectin distribution campaigns leading to rapid population-wide decreases in morbidity and mortality indicate that an oral agent effective in all phases of COVID-19 has been identified. Furthermore, results from numerous controlled prophylaxis trials report significantly reduced risks of contracting COVID-19 with the regular use of ivermectin. Meta-analyses based on 18 randomized controlled treatment trials of ivermectin in COVID-19 have found large, statistically significant reductions in mortality, time to clinical recovery, and time to viral clearance. Multiple, large “natural experiments” occurred in regions that initiated “ivermectin distribution” campaigns followed by tight, reproducible, temporally associated decreases in case counts and case fatality rates compared with nearby regions without such campaigns. Numerous prophylaxis trials demonstrate that regular ivermectin use leads to large reductions in transmission. Therapeutic Advances:Ī large majority of randomized and observational controlled trials of ivermectin are reporting repeated, large magnitude improvements in clinical outcomes. Data Sources:ĭata were sourced from published peer-reviewed studies, manuscripts posted to preprint servers, expert meta-analyses, and numerous epidemiological analyses of regions with ivermectin distribution campaigns.
Given some have not passed peer review, several expert groups including Unitaid/World Health Organization have undertaken a systematic global effort to contact all active trial investigators to rapidly gather the data needed to grade and perform meta-analyses. Recently, evidence has emerged that the oral antiparasitic agent ivermectin exhibits numerous antiviral and anti-inflammatory mechanisms with trial results reporting significant outcome benefits. The majority of trialed agents have failed to provide reproducible, definitive proof of efficacy in reducing the mortality of COVID-19 with the exception of corticosteroids in moderate to severe disease. In addition, a multitude of both novel and repurposed therapeutic agents were used empirically and studied within clinical trials. The work cannot be changed in any way or used commercially without permission from the journal.Īfter COVID-19 emerged on U.S shores, providers began reviewing the emerging basic science, translational, and clinical data to identify potentially effective treatment options.
This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. Off-Label Use: This manuscript includes discussion of off-label use in COVID-19 of the FDA-approved medication ivermectin.
Analysis and interpretation of data: Paul Marik, P. Acquisition of data: Paul Marik and Jose Iglesias. Meduri have contributed equally to this work. The authors have no conflicts of interest to declare. The contents of this commentary do not represent the views of the US Department of Veterans Affairs or the US Government. Meduri's contribution is the result of work supported with the resources and use of facilities at the Memphis VA Medical Center. *Address for correspondence: Pierre Kory, MD, MPA, Front-Line Covid-19 Critical Care, 2002 L St NW, Suite 500, Washington, D.C 20036.
1Front-Line Covid-19 Critical Care Alliance, Madison, WI ĢMemphis VA Medical Center-University of Tennessee Health Science Center, Pulmonary, Critical Care, and Research Services, Memphis, TN ģUniversity of Texas Health Science Center, Critical Care Service, Houston, TX ĤDepartment of Medicine, Hackensack School of Medicine, Seton Hall, NJ andĥEastern Virginia Medical School, Division of Pulmonary and Critical Care, Norfolk, VA.