Review of the Emerging Evidence Demonstrating the Efficacy of Ivermectin in the Prophylaxis and Treatment of COVID-19
Authors: Pierre Kory
Gianfranco Umberto Meduri
Joseph Varon
Jose Iglesias
Paul E Marik
Journal: American Journal of Therapeutics (2021)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: COVID-19; treatment options; corticosteroids; ivermectin; antiviral

Abstract:  Background: After COVID-19 emerged on U.S shores, providers began reviewing the emerging basic science, translational, and clinical data to identify potentially effective treatment options. In addition, a multitude of both novel and repurposed therapeutic agents were used empirically and studied within clinical trials. Areas of uncertainty: 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. Recently, evidence has emerged that the oral antiparasitic agent ivermectin exhibits numerous antiviral and anti-inflammatory mechanisms with trial results reporting significant outcome benefits. 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. Data sources: Data 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. Therapeutic advances: A large majority of randomized and observational controlled trials of ivermectin are reporting repeated, large magnitude improvements in clinical outcomes. Numerous prophylaxis trials demonstrate that regular ivermectin use leads to large reductions in transmission. 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. Conclusions: 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. Furthermore, results from numerous controlled prophylaxis trials report significantly reduced risks of contracting COVID-19 with the regular use of ivermectin. 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. 

Retracted: No

PubPeer comments:
 See https: blog.frontiersin.org 2021 03 02 2-march-2021-media-statement and https: www.the-scientist.com news-opinion frontiers-pulls-special-covid-19-issue-after-content-dispute-68721 and https: www.the-scientist.com news-opinion frontiers-removes-controversial-ivermectin-paper-pre-publication-68505 for some backgrounds about (an earlier version of) this article. , 
 See letter to editor published ahead-of-print :  Inaccurate Real-World Data Does Not Provide Real-World Answers Buffet, Gabriela MD; Mendoza-Sassi, Raul MD; Fysekidis, Marinos MD American Journal of Therapeutics: June 29, 2021 - Volume - Issue - doi: 10.1097 MJT.0000000000001415 , 
 Expression of concern. h t [Retraction Watch] .  ,