Ivermectin
SYNOPSIS
Ivermectin is an effective treatment for COVID-19. Treatment is more effective when used early. Meta analysis using the most serious outcome reported shows 66% [53‑76%] and 86% [75‑92%] improvement for early treatment and prophylaxis, with similar results after exclusion based sensitivity analysis and restriction to peer-reviewed studies or Randomized Controlled Trials.
TITLE
Ivermectin for COVID-19: real-time meta analysis of 65 studies
CITATION
(2021). Ivermectin for COVID-19: real-time meta analysis of 65 studies, Covid Analysis, Oct 4, 2021, Version 127. Retrieved from https://ivmmeta.com/
SUMMARY
We analyze all significant studies concerning the use of ivermectin for COVID-19. Search methods, inclusion criteria, effect extraction criteria (more serious outcomes have priority), all individual study data, PRISMA answers, and statistical methods are detailed in Appendix 1. We present random effects meta-analysis results for all studies, for studies within each treatment stage, for mortality results, for COVID-19 case results, for viral clearance results, for peer-reviewed studies, for Randomized Controlled Trials (RCTs), and after exclusions.
We also perform a simple analysis of the distribution of study effects. If treatment was not effective, the observed effects would be randomly distributed (or more likely to be negative if treatment is harmful). We can compute the probability that the observed percentage of positive results (or higher) could occur due to chance with an ineffective treatment (the probability of >= k heads in n coin tosses, or the one-sided sign test / binomial test). Analysis of publication bias is important and adjustments may be needed if there is a bias toward publishing positive results.
TAGS
SYNOPSIS
Evidence is not sufficiently strong to either promote or refute the efficacy of IVM, DOXY, or their combination in COVID-19 management.
TITLE
Safety and Efficacy of Ivermectin and Doxycycline Monotherapy and in Combination in the Treatment of COVID-19: A Scoping Review
CITATION
Bhowmick S, Dang A, Vallish BN, Dang S. (2021). Safety and Efficacy of Ivermectin and Doxycycline Monotherapy and in Combination in the Treatment of COVID-19: A Scoping Review. Drug Saf. 44(6):635-644. doi: 10.1007/s40264-021-01066-y. Epub 2021 Apr 16. PMID: 33864232; PMCID: PMC8051548.
SUMMARY
Ivermectin (IVM) and doxycycline (DOXY) have demonstrated in-vitro activity against SARS-CoV-2, and have a reasonable safety profile. The objective of this systematic review was to explore the evidence in the literature on the safety and efficacy of their use as monotherapy and combination therapy in COVID-19 management.
TAGS
SYNOPSIS
Ivermectin is an FDA-approved antiparasitic agent, being currently investigated in COVID-19 patients.
TITLE
Ivermectin: an award-winning drug with expected antiviral activity against COVID-19
CITATION
Formiga FR, Leblanc R, de Souza Rebouças J, Farias LP, de Oliveira RN, Pena L. (2021). Ivermectin: an award-winning drug with expected antiviral activity against COVID-19. J Control Release. 329:758-761. doi: 10.1016/j.jconrel.2020.10.009. Epub 2020 Oct 7. PMID: 33038449; PMCID: PMC7539925.
SUMMARY
Ivermectin is an FDA-approved broad-spectrum antiparasitic agent with demonstrated antiviral activity against a number of DNA and RNA viruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Despite this promise, the antiviral activity of ivermectin has not been consistently proven in vivo. While ivermectin’s activity against SARS-CoV-2 is currently under investigation in patients, insufficient emphasis has been placed on formulation challenges. Here, we discuss challenges surrounding the use of ivermectin in the context of coronavirus disease-19 (COVID-19) and how novel formulations employing micro- and nanotechnologies may address these concerns.
TAGS
SYNOPSIS
Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
TITLE
The broad spectrum host-directed agent ivermectin as an antiviral for SARS-CoV-2 ?
CITATION
Jans DA, Wagstaff KM. (2021). The broad spectrum host-directed agent ivermectin as an antiviral for SARS-CoV-2? Biochem Biophys Res Commun. 538:163-172. doi: 10.1016/j.bbrc.2020.10.042. Epub 2020 Oct 21. PMID: 33341233; PMCID: PMC7577703.
SUMMARY
FDA approved for parasitic indications, the small molecule ivermectin has been the focus of growing attention in the last 8 years due to its potential as an antiviral. We first identified ivermectin in a high throughput compound library screen as an agent potently able to inhibit recognition of the nuclear localizing Human Immunodeficiency Virus-1 (HIV-1) integrase protein by the host importin (IMP) α/β1 heterodimer, and recently demonstrated its ability to bind directly to IMPα to cause conformational changes that prevent its function in nuclear import of key viral as well as host proteins. Cell culture experiments have shown robust antiviral action towards a whole range of viruses, including HIV-1, dengue, Zika and West Nile Virus, Venezuelan equine encephalitis virus, Chikungunya, pseudorabies virus, adenovirus, and SARS-CoV-2 (COVID-19). Close to 70 clinical trials are currently in progress worldwide for SARS-CoV-2. Although few of these studies have been completed, the results that are available, as well as those from observational/retrospective studies, indicate clinical benefit. Here we discuss the case for ivermectin as a host-directed broad-spectrum antiviral agent, including for SARS-CoV-2.
TAGS
SYNOPSIS
The authors declare that there are no known competing financial interests or personal relationships that could have appeared to influence the work described in this paper.
TITLE
A five-day course of ivermectin for the treatment of COVID-19 may reduce the duration of illness
CITATION
Ahmed S, Karim MM, Ross AG, Hossain MS, Clemens JD, Sumiya MK, Phru CS, Rahman M, Zaman K, Somani J, Yasmin R, Hasnat MA, Kabir A, Aziz AB, Khan WA. (2021). A five-day course of ivermectin for the treatment of COVID-19 may reduce the duration of illness. Int J Infect Dis. 103:214-216. doi: 10.1016/j.ijid.2020.11.191. Epub 2020 Dec 2. PMID: 33278625; PMCID: PMC7709596.
SUMMARY
Ivermectin, a US Food and Drug Administration-approved anti-parasitic agent, was found to inhibit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication in vitro. A randomized, double-blind, placebo-controlled trial was conducted to determine the rapidity of viral clearance and safety of ivermectin among adult SARS-CoV-2 patients. The trial included 72 hospitalized patients in Dhaka, Bangladesh, who were assigned to one of three groups: oral ivermectin alone (12 mg once daily for 5 days), oral ivermectin in combination with doxycycline (12 mg ivermectin single dose and 200 mg doxycycline on day 1, followed by 100 mg every 12 h for the next 4 days), and a placebo control group. Clinical symptoms of fever, cough, and sore throat were comparable among the three groups. Virological clearance was earlier in the 5-day ivermectin treatment arm when compared to the placebo group (9.7 days vs 12.7 days; p = 0.02), but this was not the case for the ivermectin + doxycycline arm (11.5 days; p = 0.27). There were no severe adverse drug events recorded in the study. A 5-day course of ivermectin was found to be safe and effective in treating adult patients with mild COVID-19. Larger trials will be needed to confirm these preliminary findings.
TAGS
SYNOPSIS
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.
TITLE
Review of the Emerging Evidence Demonstrating the Efficacy of Ivermectin in the Prophylaxis and Treatment of COVID-19
CITATION
Pierre Kory, Gianfranco Umberto Meduri, Joseph Varon, Jose Iglesias, Paul E. Marik. (2021). Review of the Emerging Evidence Demonstrating the Efficacy of Ivermectin in the Prophylaxis and Treatment of COVID-19. American Journal of Therapeutics. 2021 May-Jun; 28(3): e299–e318. doi: 10.1097/MJT.0000000000001377
SUMMARY
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.
TAGS
SYNOPSIS
Ivermectin is an inhibitor of the COVID-19 causative virus (SARS-CoV-2) in vitro. A single treatment able to effect ~5000-fold reduction in virus at 48 h in cell culture.
TITLE
The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro
CITATION
Leon Caly, Julian D. Druce, Mike G. Catton, David A. Jans, Kylie M. Wagstaff. (2020). The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro, Antiviral Research, Volume 178, 104787.ISSN 0166-3542. https://doi.org/10.1016/j.antiviral.2020.104787.
SUMMARY
Abstract: Although several clinical trials are now underway to test possible therapies, the worldwide response to the COVID-19 outbreak has been largely limited to monitoring/containment. We report here that Ivermectin, an FDA-approved anti-parasitic previously shown to have broad-spectrum anti-viral activity in vitro, is an inhibitor of the causative virus (SARS-CoV-2), with a single addition to Vero-hSLAM cells 2 h post infection with SARS-CoV-2 able to effect ~5000-fold reduction in viral RNA at 48 h. Ivermectin therefore warrants further investigation for possible benefits in humans.